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Li X, Liu M, Ye Q, Zhu J, Zhao W, Pan H, Wang D. Association between weight change across adulthood and risk of chronic kidney disease: NHANES 1999-2020. Ren Fail 2025; 47:2448261. [PMID: 39894937 PMCID: PMC11792130 DOI: 10.1080/0886022x.2024.2448261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 12/05/2024] [Accepted: 12/25/2024] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND Obesity is a recognized risk factor for chronic kidney disease (CKD), but whether weight change is associated with CKD remains unclear. This research aimed to investigate the relationship between weight change patterns across adulthood and the risk of CKD. METHODS Data for 34,187 adults participating in the National Health and Nutrition Examination Survey 1999-2020 were analyzed. The weight change patterns of participants were assessed across different time intervals, including transitions from obesity to non-obesity, non-obesity to obesity, and remaining stable obesity. Absolute weight changes were also analyzed, categorizing participants into various weight gain and loss groups. Furthermore, stratified analyses were conducted to explore potential interactions between age, sex, and smoking status about CKD risk. RESULTS The study found that individuals transitioning from obesity to non-obesity, non-obesity to obesity, and remaining stable obesity had an elevated risk of developing CKD throughout adulthood compared to those maintaining stable non-obesity weight patterns. Moreover, a J-shaped or U-shaped relationship was observed between CKD risk and absolute weight changes, with both extreme weight gain (≥20 kg) and substantial weight loss (>2.5 kg) associated with increased CKD risk. Stratified analyses revealed that age and sex played significant roles in these associations, with stronger effects observed among participants under 60 years at baseline. CONCLUSIONS This study underscores the link between weight change across adulthood and the risk of CKD. Maintaining a stable weight and avoiding extreme weight fluctuations may reduce CKD risk. These insights can be considered when developing CKD prevention and management strategies.
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Affiliation(s)
- Xunliang Li
- Department of Nephrology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Mengqian Liu
- Department of Nephrology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
| | - Qihui Ye
- School of Nursing, Anhui Medical University, Hefei, China
| | - Jiaxin Zhu
- Department of Nephrology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
| | - Wenman Zhao
- Department of Nephrology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
| | - Haifeng Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Deguang Wang
- Department of Nephrology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Center for Big Data and Population Health of IHM, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- School of Nursing, Anhui Medical University, Hefei, China
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Suwabe T, Torres VE, Vaughan LE, Madsen CD, Harris PC, Shimada Y, Nakatani S, Hoshino J, Nishio S, Mochizuki T, Kanda E, Hanafusa N, Abe M, Muto S. Association Between Body Mass Index and Age at End-Stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease in the United States and Japan. Mayo Clin Proc 2025:S0025-6196(24)00695-5. [PMID: 40392171 DOI: 10.1016/j.mayocp.2024.12.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/27/2024] [Accepted: 12/18/2024] [Indexed: 05/22/2025]
Abstract
OBJECTIVE To evaluate the association between body mass index (BMI) and age at initiation of renal replacement therapy (RRT) of patients with autosomal dominant polycystic kidney disease (ADPKD) in the United States and Japan, 2 populations with different dietary habits and BMIs. METHODS We performed a cross-sectional analysis using data from the United States Renal Data System (USRDS) and the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) to compare age, BMI, and other clinical characteristics of the patients who initiated RRT in the 2 countries between January 1, 2006, and December 31, 2007. RESULTS This study included 3556 patients (1877 men and 1679 women) with RRT from the USRDS (n=2491) and JRDR (n=1065). Mean ages at RRT were 56.6±13.1 years in the United States and 61.6±12.5 years in Japan (P<.001). The BMI was 28.2±7.1 kg/m2 in the USRDS and 22.0±3.3 kg/m2 in the JRDR (P<.001). Japanese participants were the oldest, followed in descending order by Asian Americans, White Americans, and African Americans. Japanese participants had the lowest BMI, followed in ascending order by Asian Americans, White Americans, and African Americans. Univariable and adjusted analyses found that BMI was significantly and inversely associated with age at RRT, both overall and separately in American and Japanese populations. CONCLUSION Lower BMI is significantly associated with older age at RRT in patients with ADPKD in both the United States and Japan. Japanese individuals had lower BMI and were older than US people of various ethnicities. Lower BMI in Japan is likely to be associated with a slower progression of ADPKD.
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Affiliation(s)
- Tatsuya Suwabe
- Department of Nephrology, Toranomon Hospital Kajigaya, Kanagawa, and Okinaka Memorial Institute, Tokyo, Japan; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Robert M. and Billie J. Pirnie Translational PKD Center, Mayo Clinic, Rochester, MN.
| | - Vicente E Torres
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Robert M. and Billie J. Pirnie Translational PKD Center, Mayo Clinic, Rochester, MN
| | - Lisa E Vaughan
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN; Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN
| | - Chuck D Madsen
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Robert M. and Billie J. Pirnie Translational PKD Center, Mayo Clinic, Rochester, MN
| | - Peter C Harris
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Robert M. and Billie J. Pirnie Translational PKD Center, Mayo Clinic, Rochester, MN
| | - Yosuke Shimada
- Infection Control Science, Juntendo University Graduate School of Medicine, and Intelligent Systems Laboratory, SECOM Co, Ltd, Tokyo, Japan
| | - Shinya Nakatani
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Junichi Hoshino
- Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan
| | - Saori Nishio
- Department of Hemodialysis and Apheresis, Hokkaido University, Hokkaido, Japan
| | | | - Eiichiro Kanda
- Department of Health Data Science, Kawasaki Medical School, Okayama, Japan; Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan
| | - Norio Hanafusa
- Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan; Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan
| | - Masanori Abe
- Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan; Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Satoru Muto
- Department of Urology, Juntendo University, Tokyo, Japan
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Nokihara M, Fujihara K, Yaguchi Y, Takizawa H, Khin L, Ferreira EDA, Sato T, Horikawa C, Kitazawa M, Matsubayashi Y, Kodama S, Sone H. The associations of body mass index and waist circumference with the risk of diabetic complications in people with type 2 diabetes mellitus. Diabetes Obes Metab 2025. [PMID: 40375805 DOI: 10.1111/dom.16461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 04/09/2025] [Accepted: 04/22/2025] [Indexed: 05/18/2025]
Abstract
AIMS To determine the associations of body mass index (BMI) and waist circumference (WC) with severe diabetic complications in patients with type 2 diabetes. MATERIALS AND METHODS In total, 114 254 participants with type 2 diabetes (82% male; mean age, 52.52 ± 8.27 years; median follow-up, 4.64 years) were enrolled from a nationwide Japanese medical claims database. Cox proportional models with multivariate adjustment were used to assess the associations of BMI and WC with treatment-requiring diabetic eye disease (TRDED), initiation of dialysis, coronary artery disease (CAD), cerebrovascular disease (CVD), heart failure (HF) and amputation. RESULTS BMI was inversely associated with TRDED, especially in women. Men with WC ≥ 95 cm had a significantly lower risk of TRDED (hazard ratio [HR] = 0.79, 95% CI = 0.69-0.91). Dialysis initiation displayed L-shaped associations with BMI and WC. The risk of CAD was significantly reduced among men with BMI < 20.0 kg/m2 (HR = 0.68, 95% CI = 0.49-0.94). HF had U-shaped associations with BMI and WC. Abdominal obesity increased CVD risk (HR = 1.36, 95% CI = 1.08-1.70). BMI ≥ 25 kg/m2/WC ≥ 90 cm significantly reduced the risk of dialysis (HR = 0.42, 95% CI = 0.29-0.62) and increased the risk of HF (HR = 1.33, 95% CI = 1.03-1.72). CONCLUSIONS BMI/WC had both positive and negative associations with diabetic complications. Therefore, each patient's BMI/WC target should be carefully determined for each diabetic complication, considering the risk of developing other diseases.
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Affiliation(s)
- Megumi Nokihara
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Kazuya Fujihara
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Yuta Yaguchi
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Hiroki Takizawa
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Laymon Khin
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Efrem D' Avila Ferreira
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Takaaki Sato
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Chika Horikawa
- Department of Health and Nutrition, University of Niigata Prefecture Faculty of Human Life Studies, Niigata, Japan
| | - Masaru Kitazawa
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Yasuhiro Matsubayashi
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Satoru Kodama
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
| | - Hirohito Sone
- Department of Hematology, Endocrinology, and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan
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Leone A, Menichetti F, Vignati L, Sileo F, De Amicis R, Foppiani A, Bertoli S, Battezzati A. Relationship between bmi and glomerular filtration rate in a large cohort initiating a weight loss program: differential contributions of fat mass, fat-free mass, and abdominal fat compartments. Nutr J 2025; 24:78. [PMID: 40350415 PMCID: PMC12067886 DOI: 10.1186/s12937-025-01150-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 05/01/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND The relationship between BMI and chronic kidney disease is controversial, likely due to the inability of BMI to accurately define body composition and adipose tissue distribution. Our objective was to evaluate the synergistic contribution of fat-free mass, fat mass, visceral (VAT) and subcutaneous (SAT) adipose tissue, to glomerular filtration rate (GFR) in a large cohort of subjects. METHODS A cross-sectional study of 9704 subjects (72% female, median age 47y, median BMI 28.1 kg/m2) was carried out. Each patient underwent an anthropometric assessment (weight, height, waist circumference, % of body fat by body skinfolds), an ultrasound measurement of VAT and SAT and blood sampling to measure metabolic syndrome (MS) parameters and serum creatinine. GFR was estimated using the EPI-CKD equation. MS was defined according to the harmonized criteria. RESULTS Among 9,704 subjects, 61.1% had a normal renal function, while 29.3% reported a reduction, from slightly to severely. The BMI was initially negatively associated with GFR in the univariate model (β = -0.32, 95% CI: -0.39, -0.25), but after adjusting for %body fat, the association was lost. We then split the BMI into its two components, Fat Mass Index (FMI) and Fat Free Mass Index (FFMI), and observed that FMI (β = -1.23, 95% CI: -1.35, -1.12) and FFMI (β = 0.79, 95% CI: 0.65, 0.92) were associated with a decrease and an increase in GFR, respectively. VAT (β = -1.83, 95% CI: -2.00, -1.67) and SAT (β = 3.21, 95% CI: 2.86, 3.57) were independently associated with a decrease and an increase in GFR, respectively. Similar results were obtained when studying the association between BMI, body composition, adipose tissue distribution, and the risk of reduced GFR (<90 ml/min/1.73 m2). Stratification by sex and MS did not substantially alter the results. A significant association between VAT and reduced GFR was observed only in women. CONCLUSIONS Our study highlights the importance of considering body composition and fat distribution when assessing renal function.
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Affiliation(s)
- Alessandro Leone
- International Center for the Assessment of Nutritional Status and the development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy.
- IRCCS Istituto Auxologico Italiano, Clinical Nutrition Unit, Department of Endocrine and Metabolic Medicine, Milan, 20100, Italy.
| | - Francesca Menichetti
- International Center for the Assessment of Nutritional Status and the development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Laila Vignati
- IRCCS Istituto Auxologico Italiano, Clinical Nutrition Unit, Department of Endocrine and Metabolic Medicine, Milan, 20100, Italy
| | - Federica Sileo
- International Center for the Assessment of Nutritional Status and the development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
- IRCCS Istituto Auxologico Italiano, Clinical Nutrition Unit, Department of Endocrine and Metabolic Medicine, Milan, 20100, Italy
| | - Ramona De Amicis
- International Center for the Assessment of Nutritional Status and the development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
- IRCCS Istituto Auxologico Italiano, Obesity Unit and Laboratory of Nutrition and Obesity Research, Department of Endocrine and Metabolic Diseases, Milan, 20145, Italy
| | - Andrea Foppiani
- International Center for the Assessment of Nutritional Status and the development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
- IRCCS Istituto Auxologico Italiano, Clinical Nutrition Unit, Department of Endocrine and Metabolic Medicine, Milan, 20100, Italy
| | - Simona Bertoli
- International Center for the Assessment of Nutritional Status and the development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
- IRCCS Istituto Auxologico Italiano, Obesity Unit and Laboratory of Nutrition and Obesity Research, Department of Endocrine and Metabolic Diseases, Milan, 20145, Italy
| | - Alberto Battezzati
- International Center for the Assessment of Nutritional Status and the development of Dietary Intervention Strategies (ICANS-DIS), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
- IRCCS Istituto Auxologico Italiano, Clinical Nutrition Unit, Department of Endocrine and Metabolic Medicine, Milan, 20100, Italy
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Lambert GW, Patel M, Lambert EA. The Influence of the Sympathetic Nervous System on Cardiometabolic Health in Response to Weight Gain or Weight Loss. Metabolites 2025; 15:286. [PMID: 40422864 DOI: 10.3390/metabo15050286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 04/17/2025] [Accepted: 04/22/2025] [Indexed: 05/28/2025] Open
Abstract
Alterations in sympathetic nervous activity are evident in response to changes in body weight. Sympathetic nervous activity and sympathetic responses to weight change are regionalized, with alterations in end organ function dependent on the changes occurring in the brain regulatory pathways invoked and in the effector organs engaged. The obesity-induced activation of the sympathetic nervous system likely contributes to the initiation and worsening of cardiometabolic risk factors, including elevated blood pressure, cardiac dysfunction, dyslipidaemia, increased fasting blood glucose, insulin resistance, and non-alcoholic steatohepatitis. Unintended weight loss, as occurs in cachexia, is driven, at least in part, by the activation of sympathetic nervous-stimulated thermogenesis. The complexity of sympathetic nervous regulation renders the use of global measures of sympathetic activity problematic and the development of targeted therapies difficult, but these are not without promise or precedent. Knowledge of the central and peripheral pathways involved in sympathetic nervous regulation has opened up opportunities for pharmacological, surgical, and device-based approaches to mitigating the burden of disease development and progression. In this narrative review, we elaborate on sympathetic activity in response to changes in body weight, the brain pathways involved, and the cardiovascular and metabolic risks associated with perturbations in regional sympathetic activity.
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Affiliation(s)
- Gavin W Lambert
- School of Health Sciences and Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn, VIC 3122, Australia
| | - Mariya Patel
- School of Health Sciences and Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn, VIC 3122, Australia
| | - Elisabeth A Lambert
- School of Health Sciences and Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn, VIC 3122, Australia
- Medical Technology Victoria (MedTechVic) Research Hub, Hawthorn, VIC 3122, Australia
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Oh SH, Kim YJ, Bae S, Jung HY, Park SY, Lim JH, Cho JH, Kim CD, Park SH, Kwon TH, Kim YJ, Liu KH, Kim YL. High-fat diet promotes lipotoxicity in the podocytes of uninephrectomized mice: a targeted lipidomics and kidney podocyte-specific analysis. Cell Death Discov 2025; 11:193. [PMID: 40268915 PMCID: PMC12019177 DOI: 10.1038/s41420-025-02419-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/06/2025] [Accepted: 03/20/2025] [Indexed: 04/25/2025] Open
Abstract
Abnormal lipid metabolism is an independent risk factor for kidney injury, significantly altering the associated gene expression, particularly in single kidney models. This study investigates the impact of high-fat diet-induced lipid metabolism on podocyte injury in uninephrectomized mice. Using targeted lipidomics analysis and podocyte-specific assays, the modification of lipid profiles attributed to a high-fat diet and the development of podocyte injury caused by lipid metabolism in mice that underwent unilateral nephrectomy were examined. Mice that underwent unilateral nephrectomy and were fed with a high-fat diet for 13 weeks exhibited progressive renal dysfunction, including the accumulation of lipid droplets in podocytes, vacuolization of tubular cells, and glomerular hypertrophy. Liquid chromatography-triple quadrupole mass spectrometry confirmed a significant increase in cholesteryl ester 20:4 levels in the podocytes of these mice. In vitro, cholesteryl ester 20:4 treatment reduced mitochondrial respiration capacity and mitochondrial glycolysis in podocytes. Furthermore, the treatment led to alterations in the protein expression levels associated with lipid metabolism and transport, mitochondrial activity, and autophagy, including ATP binding cassette subfamily A member 1 (ABCA1), carnitine palmitoyltransferase 1 A (CPT1A), acyl-CoA cholesterol acyltransferase (ACAT), nuclear respiratory factor ½ (NRF½), dynamin-1-like protein (DRP1), and p62. Transcriptome sequencing analysis revealed impaired gene expression, which was associated with the progression of renal fibrosis in unilateral nephrectomy mice with a high-fat diet. Specifically, the expression of matrix metalloproteinases and collagen genes, including fibronectin and collagen IV, was upregulated, indicating fibrosis progression. In conclusion, lipidomics analysis identifies cholesteryl ester 20:4 as a key lipid metabolite accumulating in podocytes, which is associated with mitochondrial dysfunction and abnormal autophagy. This accumulation potentially contributes to structural and functional deterioration in the kidney and highlights its role in kidney damage and its potential as a therapeutic target in metabolic kidney diseases.
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Affiliation(s)
- Se-Hyun Oh
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea
| | - You-Jin Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea
| | - Subin Bae
- BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea
| | - Hee-Yeon Jung
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - So-Young Park
- BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea
- Mass Spectrometry Based Convergence Research Institute, Kyungpook National University, Daegu, Republic of Korea
| | - Jeong-Hoon Lim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea
| | - Jang-Hee Cho
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea
| | - Chan-Duck Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Sun-Hee Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Tae-Hwan Kwon
- Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Yong-Jin Kim
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Kwang-Hyeon Liu
- BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea.
- Mass Spectrometry Based Convergence Research Institute, Kyungpook National University, Daegu, Republic of Korea.
| | - Yong-Lim Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
- Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea.
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Sun Y, Li Z, Feng N. Association of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and chronic kidney disease in elderly insights from NHANES. Sci Rep 2025; 15:12611. [PMID: 40221576 PMCID: PMC11993742 DOI: 10.1038/s41598-025-96299-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel lipid index. Prior research has established a connection between lipid irregularities and chronic kidney disease (CKD). This study aims to establish a possible link between NHHR and CKD. Data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2003 to 2016 was used to examine the relationship between NHHR and CKD among the elderly population. This research utilized weighted logistic regression, smoothed curve fitting and subgroup analyses along with interaction tests to evaluate the association between NHHR and CKD. The findings reveal a positive correlation between NHHR and CKD in fully adjusted Model 3. Besides, NHHR had a J-curve relationship with CKD. Subgroup analysis indicated that compared with those with lower body mass index (BMI), individuals with higher BMI are more prone to CKD. Research has shown that increased NHHR levels are associated with a higher likelihood of developing CKD in individuals aged above 60 in the United States. NHHR's role in lipid metabolism suggests it might be an effective marker for tracking CKD's progression.
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Affiliation(s)
- Yifan Sun
- Department of Urology, Jiangnan University Medical Center, Wuxi, China
| | - Zhou Li
- Department of Urology, Nanjing Medical University, Wuxi No.2 Hospital, Wuxi, China
| | - Ninghan Feng
- Department of Urology, Jiangnan University Medical Center, Wuxi, China.
- Department of Urology, Nanjing Medical University, Wuxi No.2 Hospital, Wuxi, China.
- Jiangnan University Medical Center, 68 Zhongshan Road, Wuxi, Jiangsu, China.
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Yoshida Y, Hagiwara Y, Ito M, Nishi H, Matsuyama Y. Association of Obesity, Visceral Fat Accumulation, and Dyslipidemia with the Risk of Chronic Kidney Disease. Intern Med 2025:4613-24. [PMID: 40222924 DOI: 10.2169/internalmedicine.4613-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/15/2025] Open
Abstract
Objective Although chronic kidney disease (CKD) is independently associated with hypertension or hyperglycemia, there is no consensus on the thresholds of obesity, dyslipidemia, or visceral fat accumulation to predict CKD onset and progression. Methods We performed a multivariable logistic regression analysis for the association of the subsequent rate of estimated glomerular filtration rate (eGFR) decline with body mass index (BMI), blood high-density lipoprotein (HDL) cholesterol and triglycerides (TG) levels on 308,174 subjects who underwent health examinations conducted by the Public Health Research Center Foundation from 2015 to 2022. In addition, a Poisson regression analysis was used to evaluate the association between the appearance of urinary protein in participants without baseline urinary protein levels and eGFR decline. Results The median age of the subjects was 46 years old, and the median observation period was approximately 3 years. An eGFR decline rate of ≥5%/year was significantly associated with low HDL-cholesterol levels (<40 mg/dL), independent of the BMI and TG levels. A high baseline BMI (≥25 kg/m2) or waist circumference (≥85 cm for men and ≥90 cm for women), high TG levels (≥150 mg/dL), and low HDL-cholesterol levels were significantly associated with new-onset proteinuria. Furthermore, the higher the baseline BMI, the higher the incidence rate ratio of new-onset proteinuria. Conclusion Independent of hyperglycemia and hypertension, dyslipidemia according to the Japanese metabolic syndrome criteria and an elevated BMI were associated with a high risk of new-onset proteinuria, and a low HDL-cholesterol level was significantly associated with a rapid eGFR decline.
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Affiliation(s)
- Yui Yoshida
- Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Japan
| | - Yasuhiro Hagiwara
- Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Japan
| | - Mari Ito
- AI/Data Science Social Implementation Laboratory, Research and Development Initiative, Chuo University, Japan
| | - Hiroshi Nishi
- Division of Nephrology and Endocrinology, The University of Tokyo, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Japan
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Nowak KL, Copeland TP, Ku E, Sarnak MJ, Gitomer B, Abebe KZ, Chapman A, Perrone R, Rahbari-Oskoui FF, Steinman T, Yu AS, Chonchol M. Overweight Status, Obesity, and Progression to ESKD in Patients with Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol 2025; 20:520-528. [PMID: 39970002 PMCID: PMC12007826 DOI: 10.2215/cjn.0000000640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 02/14/2025] [Indexed: 02/21/2025]
Abstract
Key Points Higher body mass index increased risk of progression to ESKD in patients with early-stage autosomal dominant polycystic kidney disease. Higher body mass index did not increase the risk of progression to ESKD in patients with late-stage autosomal dominant polycystic kidney disease. Background Prior research has linked higher body mass index (BMI) and greater visceral adiposity with more rapid progression of early-stage autosomal dominant polycystic kidney disease (ADPKD). We now evaluate the association between overweight and obesity in patients with early- and late-stage ADPKD with progression to ESKD. Methods Participants with early-stage ADPKD (study A; N =556; eGFR: 91±17 ml/min per 1.73 m2) and late-stage ADPKD (study B; N =483; eGFR: 48±12 ml/min per 1.73 m2) who participated in the Halt Progression of Polycystic Kidney Disease (HALT) polycystic kidney disease trials were categorized by BMI as normal weight (18.5–24.9 kg/m2; ref; n =357), overweight (25.0–29.9 kg/m2; n =384), or obese (≥30 kg/m2; n =298). Kaplan–Meier survival analysis and multivariate Cox proportional hazard models were used to determine the association of baseline BMI as a continuous and categorical variable with risk of ESKD (according to the United States Renal Data System) over a median (interquartile range) follow-up period of 12.2 (7.5–13.3; study A) and 7.3 (5.1–11.7; study B) years (primary outcome). All-cause mortality (National Death Index) was also considered as a competing risk (Fine and Gray method). Results The number of ESKD events was greater with overweight (n =24) and obesity (n =23) in HALT study A versus normal weight (n =12) but not in HALT study B (normal weight: n =89, overweight: n =102, obese: n =92). In fully adjusted models, higher BMI was associated with risk of progression to ESKD in study A (hazard ratio [HR (95% confidence interval)], 1.09 [1.03 to 1.15] per unit higher BMI) but not in study B (HR, 0.98 [0.96 to 1.00]). Obesity was associated with increased risk of ESKD (HR, 2.71 [1.22 to 6.02] versus normal weight) in study A only. Results were similar when considering death as a competing risk. Conclusions Higher BMI, particularly obesity, increased the risk of progression to ESKD in patients with early-stage ADPKD but not in those with late-stage ADPKD.
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Affiliation(s)
- Kristen L. Nowak
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Timothy P. Copeland
- Division of Nephrology, Department of Medicine University of California-San Francisco, San Francisco, California
| | - Elaine Ku
- Division of Nephrology, Department of Medicine University of California-San Francisco, San Francisco, California
- Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California
| | - Mark J. Sarnak
- Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts
| | - Berenice Gitomer
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Kaleab Z. Abebe
- Division of General Internal Medicine, Department of Medicine, and Center for Biostatistics and Qualitative Methodology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Arlene Chapman
- Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Ronald Perrone
- Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts
| | | | - Theodore Steinman
- Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Alan S.L. Yu
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas
| | - Michel Chonchol
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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10
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Julián MT, Codina P, Lupón J, Zamora E, Pérez-Montes de Oca A, Domingo M, Santiago-Vacas E, Borrellas A, Ruiz-Cueto M, González-Gallego C, Troya M, Romero-González GA, Alonso N, Bayes-Genis A. Long-term trajectory of estimated glomerular filtration rate in ambulatory patients with type 2 diabetes and heart failure: clinical insights and prognostic implications. Cardiovasc Diabetol 2025; 24:104. [PMID: 40045364 PMCID: PMC11884049 DOI: 10.1186/s12933-025-02632-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 02/05/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Although previous studies have evaluated renal function decline in patients with heart failure (HF), there is limited evidence on long-term renal trajectories, especially in patients with concomitant HF and type 2 diabetes (T2D). This study aims to provide a detailed analysis of renal function decline over an extended follow-up period in a well-characterized cohort of patients with HF and T2D. METHODS This is a post hoc subanalysis of a prospective registry involving ambulatory patients with HF and T2D referred to a specialized HF clinic. The estimated glomerular filtration rate (eGFR) was assessed at baseline and during scheduled follow-up visits every three months using the Chronic Kidney Disease Epidemiology Collaboration formula. Loess curves were plotted for predefined subgroups, and multivariable longitudinal Cox regression analyses were performed to evaluate the associations between eGFR trajectories and all-cause mortality. RESULTS A total of 1,114 patients with HF and T2D were included, with a mean age of 69.3 ± 10.3 years, and 68.2% were men. In total, 10,830 scheduled creatinine measurements were analysed, with a mean of 15.8 ± 9.4 measurements per patient. A significant progressive decline in the eGFR was observed, with an average annual rate of - 2.05 (95% CI - 2.11 to - 1.95, p < 0.001) ml/min/1.73 m2. Subgroup analysis indicated that older age, nonischaemic HF aetiology, HFpEF or HFmrEF, poor glycaemic control, and higher baseline eGFRs were associated with a more pronounced decline in renal function. Furthermore, a decrease in the eGFR was independently associated with an increased risk of all-cause mortality. CONCLUSIONS This study offers novel insights into long-term renal function trajectories in patients with HF and T2D and identifies key clinical factors associated with accelerated renal decline. Future research is warranted to validate these results in larger, more diverse cohorts and to explore potential therapeutic interventions.
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Affiliation(s)
- Maria Teresa Julián
- Department of Endocrinology and Nutrition and Heart Failure Clinic, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Pau Codina
- Heart Failure Clinic and Cardiology Department, Hospital Germans Trias i Pujol, Badalona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona (UAB), Carretera del Canyet s/n, 08916, Barcelona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
| | - Josep Lupón
- Heart Failure Clinic and Cardiology Department, Hospital Germans Trias i Pujol, Badalona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona (UAB), Carretera del Canyet s/n, 08916, Barcelona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
| | - Elisabet Zamora
- Heart Failure Clinic and Cardiology Department, Hospital Germans Trias i Pujol, Badalona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona (UAB), Carretera del Canyet s/n, 08916, Barcelona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
| | | | - Mar Domingo
- Heart Failure Clinic and Cardiology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Evelyn Santiago-Vacas
- Heart Failure Clinic and Cardiology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Andrea Borrellas
- Heart Failure Clinic and Cardiology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | - María Ruiz-Cueto
- Heart Failure Clinic and Cardiology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Carlos González-Gallego
- Department of Endocrinology and Nutrition and Heart Failure Clinic, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Maribel Troya
- Heart Failure Clinic and Nephrology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | | | - Nuria Alonso
- Department of Endocrinology and Nutrition and Heart Failure Clinic, Hospital Germans Trias i Pujol, Badalona, Spain.
- Department of Medicine, Universitat Autònoma de Barcelona (UAB), Carretera del Canyet s/n, 08916, Barcelona, Spain.
- Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
| | - Antoni Bayes-Genis
- Heart Failure Clinic and Cardiology Department, Hospital Germans Trias i Pujol, Badalona, Spain.
- Department of Medicine, Universitat Autònoma de Barcelona (UAB), Carretera del Canyet s/n, 08916, Barcelona, Spain.
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
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11
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Richards J, Dorand MF, Paszkowiak M, Ahmed S, McCorkle C, Kathuria P. Significantly higher rates of KIDINS220 polymorphisms in patients with obesity and end-stage renal disease. OBESITY PILLARS 2025; 13:100155. [PMID: 39801599 PMCID: PMC11719405 DOI: 10.1016/j.obpill.2024.100155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 12/04/2024] [Accepted: 12/05/2024] [Indexed: 01/16/2025]
Abstract
Background Kinase D-interacting substrate of 220 kDa ("KIDINS220") is an integral plasma membrane protein essential to signaling throughout the body; abnormalities are linked to a variety of disorders, including obesity, but have never been directly linked to chronic- or end-stage renal disease. Methods Retrospective chart review identified patients with severe obesity who presented for pre-kidney transplant weight management. 20 individuals met criteria for testing for genetic causes of obesity. A χ2 test of independence was utilized to compare genetic mutation rates in this cohort to all individuals tested nationally. Results This case series presents a cohort of patients with severe obesity and end-stage renal disease who were subsequently found to have a significantly higher rate of KIDINS220 mutations (20 %, χ2 = 27.8, p < 0.0001) compared to the national positivity rate of all individuals tested for genetic causes of obesity. Conclusions Mutations within KIDINS220 may play a modulatory role in the progression of chronic kidney disease in patients with obesity, as evidenced by this small retrospective study. The relationship between KIDINS200, kidney disease, and obesity is complex and requires further study, but may represent a potential therapeutic target in the future.
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Affiliation(s)
- Jesse Richards
- Department of Internal Medicine, University of Oklahoma School of Community Medicine, 4502 E. 41st Street, Tulsa, OK, 74135, USA
| | - Madisen Fae Dorand
- Department of Internal Medicine, University of Oklahoma School of Community Medicine, 4502 E. 41st Street, Tulsa, OK, 74135, USA
| | - Maria Paszkowiak
- College of Medicine, University of Oklahoma School of Community Medicine, 4502 E. 41st Street, Tulsa, OK, 74135, USA
| | - Sana Ahmed
- College of Medicine, University of Oklahoma School of Community Medicine, 4502 E. 41st Street, Tulsa, OK, 74135, USA
| | - Courtney McCorkle
- College of Medicine, University of Oklahoma School of Community Medicine, 4502 E. 41st Street, Tulsa, OK, 74135, USA
| | - Pranay Kathuria
- Department of Nephrology, University of Oklahoma School of Community Medicine, 4502 E. 41st Street, Tulsa, OK, 74135, USA
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12
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Lin HYH, Chen IY, Wang TM, Yen CH, Chen Y, Chen YH, Dai DF, Huang JF, Chiu YW, Yang MY. The Role of Mitochondrial AKT1 Signaling in Renal Tubular Injury of Metabolic Syndrome. Kidney Int Rep 2025; 10:906-920. [PMID: 40225378 PMCID: PMC11993225 DOI: 10.1016/j.ekir.2024.12.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 12/02/2024] [Accepted: 12/10/2024] [Indexed: 04/15/2025] Open
Abstract
Introduction Metabolic syndrome (MetS) is increasingly recognized as a contributor to kidney disease, yet the underlying mechanisms remain poorly defined. Recent studies suggest a pivotal role for mitochondrial dysfunction in renal injury. We hypothesized that mitochondrial AKT1 signaling in renal tubules plays a critical role in MetS-related kidney injuries. Methods MetS was induced in a 8-week-old C57BL/6 male mice using a high-fat diet (HFD) for 4 months compared with controls on a standard chow diet. Additional experiments were conducted in DB/DB diabetic mice and their controls (WT and DB/WT) to validate findings. Renal metabolic parameters, mitochondrial AKT1 signaling, and markers of kidney injury were assessed. Results MetS mice exhibited significant weight gain, altered glucose handling, and decreased energy expenditure. Although kidney size and basic renal function (blood urea nitrogen [BUN], creatinine) were unchanged, markers of renal damage, including proteinuria (P = 0.0002) and KIM-1 (P < 0.0001) were elevated. Histological analyses showed increased tubular injury (P < 0.0001) and glomerulosclerosis (P = 0.0004). Transmission electron microscopy revealed aberrant mitochondria (P < 0.001), with reduced cristae length (P = 0.012) and numbers (P < 0.001). Immunohistochemistry, immunofluorescence, and Western blot analysis confirmed increased phosphorylated AKT1 (pAKT1) in the mitochondria of renal tubules (P = 0.0474), findings corroborated in DB/DB mice. This translocation of pAKT1 into mitochondria correlated with decreased cell viability upon inhibition of heat shock protein 90, indicating a dependency on mitochondrial AKT1 for cell survival. Conclusion These findings underscore the mechanistic link between mitochondrial AKT1 signaling and renal tubular injury in MetS. Targeting mitochondrial dysfunction may offer new avenues for preventing and treating kidney diseases in patients with MetS.
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Affiliation(s)
- Hugo Y.-H. Lin
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - I-Ya Chen
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tzu-Ming Wang
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Hung Yen
- Graduate Institute of Natural Product, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yumay Chen
- School of Medicine, University of California, Irvine, California, USA
| | - Yen-Hua Chen
- School of Medicine, Doctoral Program of Clinical and Experimental Medicine, Institute of Biomedical Sciences, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Dao-Fu Dai
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Wen Chiu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Yu Yang
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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13
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Kaewput W, Thongprayoon C, Suppadungsuk S, Tangpanithandee S, Wathanavasin W, Qureshi F, Cheungpasitporn W. Impact of obesity on in-hospital outcomes in peritoneal dialysis patients: insights from a nationwide analysis. Int Urol Nephrol 2025:10.1007/s11255-025-04438-w. [PMID: 40021564 DOI: 10.1007/s11255-025-04438-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 02/21/2025] [Indexed: 03/03/2025]
Abstract
BACKGROUND Obesity is a growing public health concern and may influence outcomes in end-stage kidney disease (ESKD) patients undergoing peritoneal dialysis (PD). However, its impact on in-hospital complications, mortality, and healthcare utilization in this population remains unclear. This study aimed to assess the association between obesity and hospitalization-related outcomes in PD patients. METHODS This study was conducted using the National Inpatient Sample to identify hospitalized ESKD patients receiving PD from the year 2003 to 2018. The in-hospital treatments, outcomes, and resource utilization were compared between obese and non-obese patients, adjusting for age, sex, race, year of hospitalization, and comorbidities. RESULTS A total of 100,523 hospitalized ESKD patients receiving PD were included in the analysis. Of these, 9890 (9.8%) had obesity diagnosis. In the adjusted analysis, obese patients had a higher need for procedures for PD catheter adjustment or removal (OR 1.29; 95% CI 1.16-1.43), hemodialysis (OR 1.28; 95% CI 1.19-1.38), and mechanical ventilation (OR 1.29; 95% CI 1.16-1.44), compared to non-obese patients. Obesity was significantly associated with higher risk of PD peritonitis (OR 1.12; 95% CI 1.06-1.19) and fluid overload (OR 1.34; 95% CI 1.23-1.45) but lower in-hospital mortality (OR 0.84; 95% CI 0.73-0.96). There was no significant difference in length of hospital stay and hospitalization cost between obese and non-obese patients. CONCLUSION Among hospitalized PD patients, obesity is associated with higher PD-related complications and increased need for interventions but is paradoxically linked to lower in-hospital mortality. These findings provide new insights into the obesity paradox in PD and highlight the need for tailored management strategies to mitigate obesity-related risks in hospitalized PD patients.
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Affiliation(s)
- Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok, 10400, Thailand
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
| | - Supawadee Suppadungsuk
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, 10540, Thailand
| | - Supawit Tangpanithandee
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA
| | - Wannasit Wathanavasin
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA
- Nephrology Unit, Department of Medicine, Charoenkrung Pracharak Hospital, Bangkok Metropolitan Administration, Bangkok, 10120, Thailand
| | - Fawad Qureshi
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA
| | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA
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14
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Harmer MJ, Wootton SA, Gilbert RD, Anderson CE. Nutritional Characterisation of Childhood Chronic Kidney Disease: Trace Element Malnutrition in Paediatric Renal Disease (TeMPeReD) Study. Nutrients 2025; 17:535. [PMID: 39940394 PMCID: PMC11820732 DOI: 10.3390/nu17030535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/26/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES In chronic kidney disease (CKD), poor nutrition is associated with poorer clinical outcomes. There are limited data on milder stages of childhood CKD. METHODS This study characterised the nutritional state of a cohort of children with CKD. RESULTS Within the cohort (mean age 10.5 years, mean eGFR = 57 mL/min/1.73 m2), obesity defined by body mass index rates was comparable to that in the general population, but central obesity (waist-to-height ratio > 0.5) was evident in 44% of children. Although average nutrient intakes for the cohort were acceptable, there was marked variability in the risk of poor nutrient intake ( CONCLUSIONS Much work is needed to optimise the nutritional status of children with CKD as an important modifiable risk factor for disease progression and other important outcomes.
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Affiliation(s)
- Matthew J. Harmer
- Southampton Children’s Hospital, Southampton SO16 6YD, UK (C.E.A.)
- School of Development and Health, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK
| | - Stephen A. Wootton
- School of Development and Health, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK
| | - Rodney D. Gilbert
- Southampton Children’s Hospital, Southampton SO16 6YD, UK (C.E.A.)
- School of Development and Health, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK
| | - Caroline E. Anderson
- Southampton Children’s Hospital, Southampton SO16 6YD, UK (C.E.A.)
- School of Development and Health, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK
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15
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He Z, Li Y, Zhang S, Yang H, Li Z, Han L, Zhou Y, Xu P, Zeng T, Yuen SKK, Zeng G, Wu W. Long-term effects of superselective renal artery embolization on renal function after percutaneous nephrolithotomy. World J Urol 2025; 43:96. [PMID: 39888403 DOI: 10.1007/s00345-025-05468-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 01/15/2025] [Indexed: 02/01/2025] Open
Abstract
OBJECTIVES To investigate the long-term impact of superselective renal artery embolization (SRAE) on renal function in cases of severe post-percutaneous nephrolithotomy (PCNL) haemorrhage, and to identify the factors associated with the long-term outcome of renal function. METHODS Patients treated with SRAE for post-PCNL hemorrhage between September 2016 and September 2021 were included. Patients' demographic and clinical data were recorded. Multiple linear regression and logistic regression were used to identify the factors related to the percentages of estimated glomerular filtration rate (eGFR) change and the risk factors of worsening renal function (WRF), respectively. RESULT A total of 80 patients were included. There was no significant change in eGFR before and after SRAE immediately within 1.45 ± 1.66 days (66.37 ± 28.45 vs. 63.86 ± 29.26 mL/min/1.73 m², p = 0.202). Patient's eGFR increased significantly from 66.37 ± 28.45 to 70.94 ± 30.48 mL/min/1.73 m² (p = 0.044) with a mean follow-up of 30.4 months after SRAE, especially in patients with compromised renal function before SRAE (β = 0.297, p = 0.039). However, BMI > 24 kg/m2 was significantly associated with the decrease of eGFR (β = -0.343, p = 0.016). 12 (15.0%) patients developed WRF, logistic regression analysis showed that BMI > 24.0 kg/m2 (OR = 4.144, p = 0.045) and atrophic renal cortex (OR = 4.180, p = 0.040) were independent risk factors of WRF. CONCLUSION SRAE is an effective treatment for post-PCNL severe haemorrhage, and is not deleterious to long term renal function. Notably, BMI > 24.0 kg/m2 and atrophic renal cortex were significant predictors of long-term WRF in SRAE patients.
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Affiliation(s)
- Zhican He
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yong Li
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Department of Urology, Tongren Second People's Hospital, Tongren, Guizhou, China
| | - Shike Zhang
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Hongcan Yang
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhen Li
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Liang Han
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yuhao Zhou
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Peng Xu
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Tao Zeng
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Steffi Kar Kei Yuen
- SH Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
| | - Guohua Zeng
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China.
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
| | - Wenqi Wu
- Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
- Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China.
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16
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Avgoustou E, Tzivaki I, Diamantopoulou G, Zachariadou T, Avramidou D, Dalopoulos V, Skourtis A. Obesity-Related Chronic Kidney Disease: From Diagnosis to Treatment. Diagnostics (Basel) 2025; 15:169. [PMID: 39857056 PMCID: PMC11763674 DOI: 10.3390/diagnostics15020169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 01/07/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Obesity has emerged as a global epidemic with far-reaching health complications, including its role as an independent risk factor for chronic kidney disease (CKD). Increasing evidence suggests that obesity contributes to CKD through multiple mechanisms, including chronic inflammation, hemodynamic alterations, insulin resistance, and lipid accumulation. These processes can culminate in histopathological changes collectively referred to as obesity-related glomerulopathy (ORG). This review aims to provide a comprehensive overview of the current knowledge regarding the prevalence, clinical manifestations, and pathophysiology of ORG. Furthermore, we emphasize the importance of identifying key biomarkers that facilitate the early detection of ORG. Finally, we explore emerging therapeutic strategies that offer promise in mitigating this growing global health crisis.
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Affiliation(s)
- Elena Avgoustou
- Second Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokratio General Hospital, Vasilissis Sofias 114, 11527 Athens, Greece; (G.D.); (D.A.)
| | - Ilektra Tzivaki
- First Department of Internal Medicine, Sismanogleio General Hospital, 37 Sismanogliou Str., 15126 Athens, Greece; (I.T.); (T.Z.); (V.D.)
| | - Garyfalia Diamantopoulou
- Second Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokratio General Hospital, Vasilissis Sofias 114, 11527 Athens, Greece; (G.D.); (D.A.)
| | - Tatiana Zachariadou
- First Department of Internal Medicine, Sismanogleio General Hospital, 37 Sismanogliou Str., 15126 Athens, Greece; (I.T.); (T.Z.); (V.D.)
| | - Despoina Avramidou
- Second Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokratio General Hospital, Vasilissis Sofias 114, 11527 Athens, Greece; (G.D.); (D.A.)
| | - Vasileios Dalopoulos
- First Department of Internal Medicine, Sismanogleio General Hospital, 37 Sismanogliou Str., 15126 Athens, Greece; (I.T.); (T.Z.); (V.D.)
| | - Alexandros Skourtis
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece;
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17
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Bai YX, Wang ZH, Lv Y, Liu J, Xu ZZ, Feng YQ, Liu GY, Yin P, Wang YT, Dong NG, Wu QP. Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multicohort study. Int J Surg 2025; 111:761-770. [PMID: 38954672 PMCID: PMC11745703 DOI: 10.1097/js9.0000000000001861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 06/10/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS This retrospective cohort study included three international cohorts. Primary analysis was conducted on adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan Union Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3569 patients from Wuhan Union Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between BF% and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts ( n =3951 and n =1265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the BF%. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.
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Affiliation(s)
- Yun-Xiao Bai
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Zi-Hao Wang
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yong Lv
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Jie Liu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Zhen-Zhen Xu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Yi-Qi Feng
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Guo-Yang Liu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Ping Yin
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan-Ting Wang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Nian-Guo Dong
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qing-Ping Wu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
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18
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Badve SV, Bilal A, Lee MMY, Sattar N, Gerstein HC, Ruff CT, McMurray JJV, Rossing P, Bakris G, Mahaffey KW, Mann JFE, Colhoun HM, Tuttle KR, Pratley RE, Perkovic V. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol 2025; 13:15-28. [PMID: 39608381 DOI: 10.1016/s2213-8587(24)00271-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/18/2024] [Accepted: 08/18/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE) and can also have kidney benefits. However, whether GLP-1 receptor agonists improve clinically important kidney outcomes remains uncertain. We aimed to comprehensively assess the effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes by performing a meta-analysis of randomised controlled trials. METHODS For this meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials that included at least 500 participants with type 2 diabetes, compared a GLP-1 receptor agonist with placebo with at least 12 months of follow-up, and reported a primary clinical kidney or cardiovascular outcome, from database inception to March 26, 2024. Post hoc, we included the SELECT trial (NCT03574597), which enrolled participants with cardiovascular disease and a BMI of 27 kg/m2 or more without diabetes. Study-level summary data were extracted independently by two authors for inclusion in this random-effects analysis. The main kidney outcome was a composite outcome, consisting of kidney failure (kidney replacement therapy or a persistent estimated glomerular filtration rate [eGFR] <15 mL/min per 1·73 m2), a sustained reduction in eGFR by at least 50% or the nearest equivalent, or death from kidney failure. The main cardiovascular outcome was MACE, consisting of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. This study is registered with PROSPERO, CRD42024528864. FINDINGS Of the 5140 records identified through the literature search, 11 trials, involving 85 373 participants (29 386 female, 55 987 male), were included in the meta-analysis. In participants with type 2 diabetes (67 769), GLP-1 receptor agonists reduced the composite kidney outcome by 18% compared with placebo (hazard ratio [HR] 0·82, 95% CI 0·73-0·93; I2 =26·41%), kidney failure by 16% (HR 0·84, 0·72-0·99; I2 =0%), MACE by 13% (HR 0·87, 0·81-0·93; I2 =49·75%), and all-cause death by 12% (HR 0·88, 0·83-0·93; I2 =0%). The effect on the composite kidney outcome (HR 0·81, 95% CI 0·72-0·92; I2 =23·11%), kidney failure (HR 0·84, 0·72-0·98; I2 =0%), MACE (HR 0·86, 0·80-0·92; I2 =48·9%), and all-cause death (HR 0·87, 0·82-0·91; I2 =0%) was similar when the SELECT trial was included, with no evidence of heterogeneity between this trial and those including participants with type 2 diabetes (pheterogeneity >0·05). There was no difference in the risk of serious adverse events, including acute pancreatitis and severe hypoglycaemia, between the GLP-1 receptor agonist and placebo groups (risk ratio [RR] 0·95, 95% CI 0·90-1·01; I2 =88·5%). However, treatment discontinuation due to adverse events occurred more frequently in the GLP-1 receptor agonist groups (RR 1·51, 95% CI 1·18-1·94; I2 =96·3%). INTERPRETATION We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events. FUNDING None.
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Affiliation(s)
- Sunil V Badve
- St George Hospital, Sydney, NSW, Australia; Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia.
| | - Anika Bilal
- AdventHealth Translational Research Institute, Orlando, FL, USA
| | - Matthew M Y Lee
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Naveed Sattar
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Hertzel C Gerstein
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
| | - Christian T Ruff
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - John J V McMurray
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - George Bakris
- American Society of Hypertension Comprehensive Hypertension Center, University of Chicago Medicine and Biological Sciences, Chicago, IL, USA
| | - Kenneth W Mahaffey
- Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA, USA
| | - Johannes F E Mann
- KfH Kidney Center, Munich, Germany; University Hospital, Friedrich-Alexander University, Erlangen, Germany
| | - Helen M Colhoun
- Institute of Genetics and Molecular Medicine, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
| | - Katherine R Tuttle
- University of Washington School of Medicine, Seattle, WA, USA; Providence Inland Northwest Health, Spokane, WA, USA
| | | | - Vlado Perkovic
- Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia
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19
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Gupta H, Bhandari U. Molecular Insight into Obesity-Associated Nephropathy: Clinical Implications and Possible Strategies for its Management. Curr Drug Targets 2025; 26:188-202. [PMID: 39411934 DOI: 10.2174/0113894501314788241008115712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 09/12/2024] [Accepted: 09/19/2024] [Indexed: 04/11/2025]
Abstract
Obesity is a significant health concern due to its rapid increase worldwide. It has been linked to the pathogenic factors of renal diseases, cancer, cardiovascular diseases, hypertension, dyslipidemia, and type 2 diabetes. Notably, obesity raises the likelihood of developing chronic kidney disease (CKD), leading to higher adult mortality and morbidity rates. This study explores the molecular mechanisms that underlie obesity-associated nephropathy and its clinical implications. Obesity-Associated Nephropathy (OAN) develops and worsens due to insulin resistance and hyperinsulinemia, which promote renal sodium reabsorption, glomerular hyperfiltration, and hypertension, leading to progressive kidney damage. Renal damage is further aggravated by persistent inflammation and redox damage, mediated by adipokines and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, stimulation of the sympathetic nervous system and the renin-angiotensin- aldosterone system (RAAS) intensifies glomerular hypertension and fibrosis. These elements cause glomerular hyperfiltration, renal hypertrophy, and progressive kidney damage. Clinical manifestations of obesity-associated nephropathy include proteinuria, reduced glomerular filtration rate (GFR), and ultimately, CKD. Management strategies currently focus on lifestyle modifications, such as weight loss through diet and exercise, which have been effective in reducing proteinuria and improving GFR. Pharmacological treatments targeting metabolic pathways, including GLP-1 receptor agonists and SGLT2 inhibitors, have shown renoprotective properties. Additionally, traditional RAAS inhibitors offer therapeutic benefits. Early detection and comprehensive management of OAN are essential to prevent its progression and lessen the burden of CKD.
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Affiliation(s)
- Himani Gupta
- Department of Pharmacology, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi, 110062, India
| | - Uma Bhandari
- Department of Pharmacology, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi, 110062, India
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20
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Zhang X, Kang K, Yan C, Feng Y, Vandekar S, Yu D, Rosenbloom ST, Samuels J, Srivastava G, Williams B, Albaugh VL, English WJ, Flynn CR, Chen Y. Association Between Patient Portal Engagement and Weight Loss Outcomes in Patients After Bariatric Surgery: Longitudinal Observational Study Using Electronic Health Records. J Med Internet Res 2024; 26:e56573. [PMID: 39652378 PMCID: PMC11667139 DOI: 10.2196/56573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/25/2024] [Accepted: 10/30/2024] [Indexed: 01/01/2025] Open
Abstract
BACKGROUND Bariatric surgery is an effective intervention for obesity, but comprehensive postoperative self-management is essential for optimal outcomes. While patient portals are generally seen as beneficial in engaging patients in health management, the link between their use and post-bariatric surgery weight loss remains unclear. OBJECTIVE This study aimed to investigate the association between patient portal engagement and postoperative BMI reduction among patients after bariatric surgery. METHODS This retrospective longitudinal study included patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy at Vanderbilt University Medical Center between January 2018 and March 2021. Patient portal engagement was measured during 4 stages: early (within 3 months after surgery), early midterm (3-6 months), late midterm (6-9 months), and late (9-12 months). Using generalized estimating equations, we estimated the associations between patients' portal engagements at these stages and the percentage of BMI reduction (%BMIR) at 3, 6, and 12 months after surgery. Covariates included duration since surgery, patient's age at the time of surgery, sex, race and ethnicity, type of bariatric surgery, severity of comorbid conditions, and socioeconomic disadvantage. RESULTS The study included 1415 patients, predominantly female (n=1145, 80.9%), with a racial composition of 76.9% (n=1088) White and 19.9% (n=282) Black. Overall, 805 (56.9%) patients underwent Roux-en-Y gastric bypass and 610 (43.1%) underwent sleeve gastrectomy. By 1 year after surgery, the median %BMIR was 31.5% (IQR 25.2%-36.8%), and the median number of active days on the patient portal was 54 (IQR 33-80). Early portal engagement was significantly associated with %BMIR at various postoperative times. Specifically, each additional 10 days of early portal engagement was associated with a 0.37% (95% CI -0.55% to -0.18%; P<.001) lower expected %BMIR at 3 months, a 1.11% (95% CI 0.82%-1.41%; P<.001) higher expected %BMIR at 6 months, and a 0.78% (95% CI 0.25%-1.31%; P=.004) higher expected %BMIR at 12 months. Furthermore, early midterm portal engagement was associated with a 0.36% (95% CI -0.69 to -0.03; P=.03) lower expected %BMIR at 6 months, but it was not significant at 12 months (P=.88). Late midterm and late portal engagement were not significantly associated with %BMIR at 12 months (P=.27 and P=.12, respectively). Furthermore, early engagement in various portal functions, such as messaging and accessing medical records, was significantly associated with a lower %BMIR at 3 months and a higher %BMIR at both 6 and 12 months (all P<.05). CONCLUSIONS Higher patient portal engagement within 3 months after surgery-suggestive of stronger adherence to postoperative instructions and improved communication with care teams-is associated with less favorable weight loss immediately after surgery but enhanced postoperative weight loss outcomes at 6 and 12 months. However, the limitations of retrospective data-driven studies highlight the need for future intervention-based studies to validate these associations and establish causality.
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Affiliation(s)
- Xinmeng Zhang
- Department of Computer Science, Vanderbilt University, Nashville, TN, United States
| | - Kaidi Kang
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Chao Yan
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Yubo Feng
- Department of Computer Science, Vanderbilt University, Nashville, TN, United States
| | - Simon Vandekar
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Danxia Yu
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - S Trent Rosenbloom
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Jason Samuels
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Gitanjali Srivastava
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, United States
- Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
- Vanderbilt Weight Loss Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Brandon Williams
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, United States
- Vanderbilt Weight Loss Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Vance L Albaugh
- Metamor Institute, Pennington Biomedical Research Center, Baton Rouge, LA, United States
| | - Wayne J English
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, United States
- Vanderbilt Weight Loss Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Charles R Flynn
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, United States
- Vanderbilt Weight Loss Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - You Chen
- Department of Computer Science, Vanderbilt University, Nashville, TN, United States
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
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21
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Abasheva D, Ortiz A, Fernandez-Fernandez B. GLP-1 receptor agonists in patients with chronic kidney disease and either overweight or obesity. Clin Kidney J 2024; 17:19-35. [PMID: 39583142 PMCID: PMC11581768 DOI: 10.1093/ckj/sfae296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Indexed: 11/26/2024] Open
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as game-changers across the cardiovascular-kidney-metabolic (CKM) spectrum: overweight/obesity, type 2 diabetes mellitus (T2DM) and associated chronic kidney disease (CKD) and cardiovascular disease (CVD). Liraglutide, semaglutide and tirzepatide are European Medicines Agency approved to improve metabolic control in T2DM and to decrease weight in persons with obesity [body mass index (BMI) ≥30 kg/m2] or with overweight (BMI ≥27 kg/m2) associated with weight-related comorbidities such as hypertension, dyslipidaemia, CVD and others. Additionally, liraglutide and semaglutide are approved to reduce CVD risk in patients with CVD and T2DM. Semaglutide is also approved to reduce CVD risk in patients with CVD and either obesity or overweight and in phase 3 clinical trials showed kidney and cardiovascular protection in patients with T2DM and albuminuric CKD (FLOW trial) as well as in persons without diabetes that had CVD and overweight/obesity (SELECT trial). Thus, nephrologists should consider prescribing GLP-1 RAs to improve metabolic control, reduce CVD risk or improve kidney outcomes in three scenarios: patients with overweight and a related comorbid condition such as hypertension, dyslipidaemia or CVD, patients with obesity and patients with T2DM. This review addresses the promising landscape of GLP-1 RAs to treat persons with overweight or obesity, with or without T2DM, within the context of CKD, assessing their safety and impact on weight, metabolic control, blood pressure and kidney and cardiovascular outcomes, as part of a holistic patient-centred approach to preserve CKM health.
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Affiliation(s)
- Daria Abasheva
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain
- RICORS2040 Madrid, Spain
- Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
| | - Alberto Ortiz
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain
- RICORS2040 Madrid, Spain
- Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
| | - Beatriz Fernandez-Fernandez
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain
- RICORS2040 Madrid, Spain
- Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
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22
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Mu Z, Li B, Chen M, Liang C, Gu W, Su J. Endoplasmic reticulum stress induces renal fibrosis in high‑fat diet mice via the TGF‑β/SMAD pathway. Mol Med Rep 2024; 30:235. [PMID: 39422027 PMCID: PMC11544397 DOI: 10.3892/mmr.2024.13360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 09/16/2024] [Indexed: 10/19/2024] Open
Abstract
The aim of the present study was to investigate the role and mechanism of endoplasmic reticulum stress (ERS) in kidney injury caused by high‑fat diet (HFD). An obese mouse model was established via HFD feeding and intervention was performed by intraperitoneal injection of the ERS inhibitor salubrinal (Sal). Changes in the body and kidney weight and serum biochemical indices of the mice were determined. Hematoxylin and eosin and Masson staining were used to observe the pathological changes of renal tissues. Reverse transcription‑quantitative PCR and western blotting were used to observe the expression of ERS‑related proteins and TGF‑β/SMAD pathway‑related proteins. Immunohistochemistry was employed to explore the distribution of these proteins. Compared with those in the control group, the weight gain, lipid metabolism disorders and deterioration of renal function in the model group were greater. Malondialdehyde was elevated and superoxide dismutase was decreased in renal tissues. The mRNA and protein levels of TGF‑β1, SMAD2/3, α‑smooth muscle actin, collagen I, glucose‑regulated protein 78 and C/EBP‑homologous protein were markedly elevated, whereas SMAD7 was markedly decreased. Sal markedly inhibited the aforementioned effects. This investigation revealed a link between ERS and renal injury caused by HFD. ERS in HFD‑fed mice triggers renal fibrosis through the TGF‑β/SMAD pathway.
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Affiliation(s)
- Zhidan Mu
- Department of Physiology and Pathophysiology, College of Basic Medicine, Dali University, Dali, Yunnan 671000, P.R. China
| | - Bin Li
- Department of Physiology and Pathophysiology, College of Basic Medicine, Dali University, Dali, Yunnan 671000, P.R. China
| | - Mingyang Chen
- Department of Physiology and Pathophysiology, College of Basic Medicine, Dali University, Dali, Yunnan 671000, P.R. China
| | - Chen Liang
- Department of Physiology and Pathophysiology, College of Basic Medicine, Dali University, Dali, Yunnan 671000, P.R. China
| | - Wei Gu
- Department of Infection Disease, First Affiliated Hospital of Dali University, Dali, Yunnan 671000, P.R. China
| | - Juan Su
- Department of Physiology and Pathophysiology, College of Basic Medicine, Dali University, Dali, Yunnan 671000, P.R. China
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23
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Iwagami M, Odani K, Saito T. Estimating and Predicting the Rate of Kidney Function Decline over 10 Years in the General Population. KIDNEY360 2024; 5:1862-1870. [PMID: 39451006 DOI: 10.34067/kid.0000000608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 09/30/2024] [Indexed: 10/26/2024]
Abstract
Key Points
This study estimated the kidney function decline rate over 10 years in the general population.We also developed a machine learning prediction model based on annual health checkup results and claims for the first 5 years.Prediction models for kidney function decline would be useful for stratifying the general population and identifying rapid decliners.
Background
We aimed to estimate the rate of kidney function decline over 10 years in the general population and develop a machine learning model to predict it.
Methods
We used the JMDC database from 2012 to 2021, which includes company employees and their family members in Japan, where annual health checks are mandated for people aged 40–74 years. We estimated the slope (average change) of eGFR over a period of 10 years. Then, using the annual health-check results and prescription claims for the first 5 years from 2012 to 2016 as predictor variables, we developed an XGBoost model, evaluated its prediction performance with the root mean squared error (RMSE), R2, and area under the receiver operating characteristic curve (AUROC) for rapid decliners (defined as the slope <−3 ml/min per 1.73 m2 per year) using five-fold cross validation, and compared these indicators with those of (1) the simple application of the eGFR slope from 2012 to 2016 and (2) the adjusted linear regression model.
Results
We included 126,424 adults (mean age, 45.2 years; male, 82.4%; mean eGFR, 79.0 ml/min per 1.73 m2 in 2016). The mean slope was −0.89 (SD, 0.96) ml/min per 1.73 m2 per year. The predictive performance of the XGBoost model (RMSE, 0.78; R2, 0.35; and AUROC, 0.89) was better than that of either the simple application of the eGFR slope from 2012 to 2016 (RMSE, 1.94; R2, −3.03; and AUROC, 0.79) or the adjusted linear regression model (RMSE, 0.81; R2, 0.30; and AUROC, 0.87).
Conclusions
We estimated the rate of kidney function decline over 10 years in the general population, as well as demonstrated that application of machine learning to annual health-check and claims data, provides better predictive performance compared with traditional methods.
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Affiliation(s)
- Masao Iwagami
- Department of Health Services Research, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
- International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba, Ibaraki, Japan
- Digital Society Division, Center for Cyber Medicine Research, University of Tsukuba, Ibaraki, Japan
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24
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El Moneem Elfedawy MA, El Sadek Elsebai SA, Tawfik HM, Youness ER, Zaki M. Adropin a candidate diagnostic biomarker for cardiovascular disease in patients with chronic kidney disease. J Genet Eng Biotechnol 2024; 22:100438. [PMID: 39674635 PMCID: PMC11703640 DOI: 10.1016/j.jgeb.2024.100438] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 10/29/2024] [Accepted: 10/30/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a chief worldwide health concern that has a substantial financial impact on health systems, high rates of mortality and morbidity as well as cardiovascular disease (CVD) is a major cause of mortality in this population. Adropin is a unique hormone encoded by the energy homeostasis-associated (Enho) gene. AIM OF THE WORK We aimed to explore the efficacy of adropin as a diagnostic candidate biomarker for CVD in patients with CKD. METHODS This is prospective study was carried out on 60 patients (Pt) with CKD and 30 age and sex matched healthy control subjects. CKD Pt were classified according to the history of CVD into two groups: Group A, Pt without history (n = 32) and Group B, Pt with history (n = 28). Serum adropin, lipids and Hs-CRP were measured by ELISA kit. Echocardiography was also investigated. Receiver operator characteristic curve (ROC) was used to determine cut-off points of adropin. Negative predict value (NPV), negative predict value (NPV) and area under curve were detected. RESULTS There were abnormal ECGs in 78.6 % of CKD patients. Adropin was significantly decreased in Group B than Group A and control group. On the other hand, serum lipids and Hs-CRP were significantly increased in Group B than Group A and control group. ROC analysis revealed that serum adropin could be used to discriminate between patients with and without CVD history at a cutoff level of > 304 with 46.4 % sensitivity and 84.4 % specificity, 74.8 % PPV, 61.2 % NPV and AUC = 0.57. Moreover, between Group A and control at a cutoff level of < 410, with 93.8 % sensitivity, 86.7 % specificity, 87.6 % PPV and 93.3 % NPV and AUC = 0.97 as well as between Group B and control group at a cutoff level of < 416, with 57.1 % sensitivity, 83.3 % specificity, 77.4 % PPV and 66 % NPV and AUC = 0.65. CONCLUSION Particularly in CKD patients, adropin may be a useful biomarker for predicting the onset of CVD. Adropin may represent a novel and useful blood marker for assessing systolic function and Spontaneous coronary artery dissection (SCAD).
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Affiliation(s)
| | | | - Hend Mohamed Tawfik
- Department of Internal Medicine, Faculty of Medicine, Al-Azher University (for girls), Egypt.
| | - Eman Refaat Youness
- Medical Biochemistry Department, Medical Research and Clinical Studies Institute - National Research Centre Cairo, Egypt.
| | - Moushira Zaki
- Biological Anthropology Department, Medical Research and Clinical Studies Institute-National Research Centre Cairo, Egypt.
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25
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Yang S, Ling J, Zhang S, Li Y, Yang G. Metabolic dysfunction, rather than obesity, is a risk factor for chronic kidney disease in Chinese population. Aging Male 2024; 27:2335158. [PMID: 38600669 DOI: 10.1080/13685538.2024.2335158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 03/21/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND Metabolic dysfunction and obesity are closely related to chronic kidney disease (CKD). However, studies on the relationship between various metabolic syndrome-body mass index (MetS-BMI) phenotypes and the risk of CKD in the Chinese population have not yet been explored. MATERIALS AND METHODS Data from the China Health and Retirement Longitudinal Study (CHARLS) 2015 were analyzed in this study. This study enrolled 12,054 participants. Participants were divided into six distinct groups according to their MetS-BMI status. Across the different MetS-BMI groups, the odd ratios (ORs) for CKD were determined using multivariable logistic regression models. RESULTS The prevalence of CKD was higher in metabolically unhealthy groups than in the corresponding healthy groups. Moreover, the fully adjusted model showed that all metabolically unhealthy individuals had an increased risk of developing CKD compared to the metabolically healthy normal weight group (OR = 1.62, p = 0.002 for the metabolically unhealthy normal weight group; OR = 1.55, p < 0.001 for the metabolically unhealthy overweight group; and OR = 1.77, p < 0.001 for the metabolically unhealthy obesity group. CONCLUSIONS This study is the first to evaluate the relationship between the MetS-BMI phenotype and renal prognosis in the Chinese population. Individuals with normal weights are at different risk of developing CKD depending on their different metabolic phenotypes.
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Affiliation(s)
- Shan Yang
- Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Jiaxiu Ling
- Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Siliang Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Yang Li
- Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Gangyi Yang
- Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
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26
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Annunziata G, Caprio M, Verde L, Carella AM, Camajani E, Benvenuto A, Paolini B, De Nicola L, Aucella F, Bellizzi V, Barberi S, Grassi D, Fogacci F, Colao A, Cicero AFG, Prodam F, Aimaretti G, Muscogiuri G, Barrea L. Nutritional assessment and medical dietary therapy for management of obesity in patients with non-dialysis chronic kidney disease: a practical guide for endocrinologist, nutritionists and nephrologists. A consensus statement from the Italian society of endocrinology (SIE), working group of the club nutrition-hormones and metabolism; the Italian society of nutraceuticals (SINut), club ketodiets and nutraceuticals "KetoNut-SINut"; and the Italian society of nephrology (SIN). J Endocrinol Invest 2024; 47:2889-2913. [PMID: 39292364 DOI: 10.1007/s40618-024-02446-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 08/19/2024] [Indexed: 09/19/2024]
Abstract
PURPOSE Chronic kidney disease (CKD) is a serious health concern with an estimated prevalence of about 13.4% worldwide. It is cause and consequence of various comorbidities, including cardiovascular diseases. In parallel, common pathological conditions closely related to ageing and unhealthy dietary habits increase the risk of CKD development and progression, including type 2 diabetes and obesity. Among these, obesity is either independent risk factor for new onset kidney disease or accelerates the rate of decline of kidney function by multiple mechanisms. Therefore, the role of diets aimed at attaining weight loss in patients with obesity is clearly essential to prevent CKD as to slow disease progression. Various dietary approaches have been licensed for the medical dietary therapy in CKD, including low-protein diet and Mediterranean diet. Interestingly, emerging evidence also support the use of low-carbohydrate/ketogenic diet (LCD/KD) in these patients. More specifically, LCD/KDs may efficiently promote weight loss, improve metabolic parameters, and reduce inflammation and oxidative stress, resulting in a dietary strategy that act globally in managing collateral conditions that are directly and indirectly related to the kidney function. CONCLUSION This consensus statement from the Italian Society of Endocrinology (SIE), working group of the Club Nutrition - Hormones and Metabolism; the Italian Society of Nutraceuticals (SINut), Club Ketodiets and Nutraceuticals "KetoNut-SINut"; and the Italian Society of Nephrology (SIN) is intended to be a guide for Endocrinologist, Nutritionists and Nephrologist who deal with the management of patients with obesity with non-dialysis CKD providing a practical guidance on assessing nutritional status and prescribing the optimal diet in order to best manage obesity to prevent CKD and its progression to dialysis.
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Affiliation(s)
- G Annunziata
- Facoltà di Scienze Umane, della Formazione e dello Sport, Università Telematica Pegaso, Via Porzio, Centro Direzionale, Isola F2, 80143, Naples, Italy
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - M Caprio
- Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Rome, Italy
- Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166, Rome, Italy
| | - L Verde
- Department of Public Health, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
| | - A M Carella
- Facoltà di Scienze Umane, della Formazione e dello Sport, Università Telematica Pegaso, Via Porzio, Centro Direzionale, Isola F2, 80143, Naples, Italy
- Internal Medicine Department, "T. Masselli-Mascia" Hospital-San Severo (Foggia), Foggia, Italy
| | - E Camajani
- Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166, Rome, Italy
| | - A Benvenuto
- Internal Medicine Department, "T. Masselli-Mascia" Hospital-San Severo (Foggia), Foggia, Italy
| | - B Paolini
- Department of Innovation, experimentation and clinical research, Unit of dietetics and clinical nutrition, S. Maria Alle Scotte Hospital, University of Siena, Siena, SI, Italy
| | - L De Nicola
- Nephrology and Dialysis Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - F Aucella
- Nephrology and Dialysis Unit, "Casa Sollievo Della Sofferenza" Foundation, Scientific Institut for Reserch and Health Care, San Giovanni Rotondo, FG, Italy
| | - V Bellizzi
- Nephrology and Dialysis Division, AORN "Sant'Anna E San Sebastiano" Hospital, Caserta, Italy
| | - S Barberi
- Department of Clinical and Molecular Medicine, Renal Unit, Sant'Andrea University Hospital, "Sapienza" University of Rome, Rome, Italy
| | - D Grassi
- Internal Medicine Unit-Val Vibrata Hospital-Sant'Omero (TE)-Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - F Fogacci
- Hypertension and Cardiovascular Risk Factors Research Centre, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40100, Bologna, Italy
- Cardiovascular Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, 40138, Bologna, Italy
| | - A Colao
- Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università Degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- Cattedra Unesco "Educazione Alla Salute e Allo Sviluppo Sostenibile", University Federico II, 80131, Naples, Italy
| | - A F G Cicero
- Hypertension and Cardiovascular Risk Factors Research Centre, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40100, Bologna, Italy
- Cardiovascular Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, 40138, Bologna, Italy
| | - F Prodam
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - G Aimaretti
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - G Muscogiuri
- Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università Degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.
- Cattedra Unesco "Educazione Alla Salute e Allo Sviluppo Sostenibile", University Federico II, 80131, Naples, Italy.
| | - L Barrea
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università Degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- Dipartimento di Benessere, Nutrizione e Sport, Università Telematica Pegaso, Centro Direzionale, Via Porzio, Isola F2, 80143, Naples, Italy
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27
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Wang Y, Liao L, Guo Q, Liao Y, Lin X, Li H, Deng L, Deng Y, Guo D, Chen K, Fang Y. The systemic inflammatory response index is associated with chronic kidney disease in patients with hypertension: data from the national health and nutrition examination study 1999-2018. Ren Fail 2024; 46:2396459. [PMID: 39311633 PMCID: PMC11421140 DOI: 10.1080/0886022x.2024.2396459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 04/04/2024] [Accepted: 08/21/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND Studies have shown that in hypertensive patients, chronic kidney disease (CKD) is associated with a poor prognosis. Inflammation is a highly important factor in the progression of CKD. Detecting systemic inflammation and intervening promptly in patients with hypertension may help reduce the risk of CKD. The systemic inflammatory response index (SIRI) is a tool used to measure the systemic inflammatory response, but its relationship with CKD in patients with hypertension remains uncertain. METHODS We utilized data from the National Health and Nutrition Examination Survey (NHANES), which was conducted between 1999 and 2018. The analysis included a total of 20,243 participants, categorized into three groups based on SIRI tertiles. Logistic regression analysis and restricted cubic spline analysis were used to examine the relationship between the SIRI and CKD. RESULTS In patients with hypertension, there was a notable relationship between the SIRI and the odds of developing CKD. After full adjustment, there was a 31% greater likelihood of developing CKD associated with each incremental increase of 1 unit in the SIRI (OR: 1.31, 95% CI: 1.24-1.39, p < 0.001). The groups with greater SIRI values exhibited greater odds of developing CKD than did the T1 group (T2: OR: 1.20, 95% CI: 1.04-1.38, p = 0.015; T3: OR: 1.69, 95% CI: 1.47-1.94, p < 0.001). CONCLUSION A high SIRI is associated with an increased risk of CKD in hypertensive patients. The greater the SIRI is, the greater the risk of CKD in hypertensive patients.
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Affiliation(s)
- Yani Wang
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Lihua Liao
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Qian Guo
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Ying Liao
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Xueqin Lin
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Huilan Li
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Lin Deng
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Yufei Deng
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Danni Guo
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Kaihong Chen
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Yong Fang
- Department of Cardiovascular Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
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Bellizzi V, Annunziata G, Albanese A, D'Alessandro C, Garofalo C, Foletto M, Barrea L, Cupisti A, Zoccali C, De Nicola L. Approaches to patients with obesity and CKD: focus on nutrition and surgery. Clin Kidney J 2024; 17:51-64. [PMID: 39583144 PMCID: PMC11581770 DOI: 10.1093/ckj/sfae291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Indexed: 11/26/2024] Open
Abstract
Obesity is recognized as a public health challenge. During the last three decades, the global age-standardized prevalence increased from 8.8% to 18.5% in women and from 4.8% to 14.0% in men, with an absolute current number of 878 million obese subjects. Obesity significantly increases per se the risk of developing disability and chronic diseases, including chronic kidney disease (CKD). Specifically, obesity acts as a major, modifiable cause of CKD onset and progression toward kidney failure; as such, it is considered by the International Society of Nephrology a major health priority. This review analyses the effectiveness, safety and practicability of non-pharmacological anti-obesity interventions in CKD as the different patient phenotypes that may take advantage of personalized approaches.
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Affiliation(s)
- Vincenzo Bellizzi
- Division of Nephrology “Sant'Anna e San Sebastiano” Hospital, Caserta, Italy
| | - Giuseppe Annunziata
- Facoltà di Scienze Umane, della Formazione e dello Sport, Università Telematica Pegaso, Naples, Italy
| | - Alice Albanese
- Bariatric Surgery Unit, Azienda Ospedale, University of Padua, Padua, Italy
| | - Claudia D'Alessandro
- Division of Nephrology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Carlo Garofalo
- Nephrology Division, University “Luigi Vanvitelli” of Naples, Naples, Italy
| | - Mirto Foletto
- Bariatric Surgery Unit, Azienda Ospedale, University of Padua, Padua, Italy
| | - Luigi Barrea
- Department of Wellbeing, Nutrition and Sport, Pegaso Telematic University, Naples, Italy
| | - Adamasco Cupisti
- Division of Nephrology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Luca De Nicola
- Nephrology Division, University “Luigi Vanvitelli” of Naples, Naples, Italy
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29
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Wakasugi M, Goto S. An increasing trend of overweight and obesity in the Japanese incident end-stage kidney disease population. Nephrology (Carlton) 2024; 29:884-894. [PMID: 39462505 PMCID: PMC11579560 DOI: 10.1111/nep.14410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 09/23/2024] [Accepted: 10/14/2024] [Indexed: 10/29/2024]
Abstract
AIM The global prevalence of overweight/obesity has been rising, and this trend is apparent in US and European incident end-stage kidney disease (ESKD) populations. We aimed to examine temporal trends in the prevalence of overweight/obesity and underweight among adult incident ESKD patients in Japan by year of dialysis initiation between 2006 and 2019 in comparison with those observed in the Japanese adult population during the same period. METHODS Using data from the Japanese Society of Dialysis Therapy Renal Data Registry and the National Health and Nutrition Survey, the sex-specific prevalence of overweight/obesity and that of underweight (BMI ≥ 25 kg/m2 and <18.5 kg/m2, respectively) were calculated, adjusted for age according to the 2019 Population Census via the direct method. Average annual percentage changes (AAPCs) and corresponding 95% confidence intervals (CIs) were calculated to examine trends. RESULTS From 2006 to 2019, the age-adjusted prevalence of overweight/obesity in the incident ESKD population increased for males (AAPC 3.36 [95% CI, 2.70 to 4.09]) and females (AAPC 2.86 [95% CI, 1.65 to 4.19]). The age-adjusted prevalence of overweight/obesity in the general population increased for males (AAPC 0.87 [95% CI, 0.26 to 1.42]) but not for females (AAPC 0.01 [95% CI, -0.55 to 0.57]). The age-adjusted prevalence of underweight in the incident ESKD population significantly decreased but was higher than that in the general population for both sexes. CONCLUSION An increasing trend of overweight/obesity was observed in the incident ESKD population in Japan. There is a pressing need to address both underweight and overweight/obesity in the incident ESKD population.
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Affiliation(s)
- Minako Wakasugi
- Department of Inter‐Organ Communication ResearchNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Shin Goto
- Division of Clinical Nephrology and RheumatologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
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30
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Sun N, Ogulur I, Mitamura Y, Yazici D, Pat Y, Bu X, Li M, Zhu X, Babayev H, Ardicli S, Ardicli O, D'Avino P, Kiykim A, Sokolowska M, van de Veen W, Weidmann L, Akdis D, Ozdemir BG, Brüggen MC, Biedermann L, Straumann A, Kreienbühl A, Guttman-Yassky E, Santos AF, Del Giacco S, Traidl-Hoffmann C, Jackson DJ, Wang DY, Lauerma A, Breiteneder H, Zhang L, O'Mahony L, Pfaar O, O'Hehir R, Eiwegger T, Fokkens WJ, Cabanillas B, Ozdemir C, Kistler W, Bayik M, Nadeau KC, Torres MJ, Akdis M, Jutel M, Agache I, Akdis CA. The epithelial barrier theory and its associated diseases. Allergy 2024; 79:3192-3237. [PMID: 39370939 DOI: 10.1111/all.16318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 10/08/2024]
Abstract
The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.
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Affiliation(s)
- Na Sun
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, P. R. China
| | - Ismail Ogulur
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yasutaka Mitamura
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Duygu Yazici
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yagiz Pat
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Xiangting Bu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Manru Li
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Xueyi Zhu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Huseyn Babayev
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Sena Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Genetics, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey
| | - Ozge Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Division of Food Processing, Milk and Dairy Products Technology Program, Karacabey Vocational School, Bursa Uludag University, Bursa, Turkey
| | - Paolo D'Avino
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Ayca Kiykim
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Pediatrics, Division of Pediatric Allergy and Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Lukas Weidmann
- Department of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Deniz Akdis
- Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
| | | | - Marie Charlotte Brüggen
- Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Alex Straumann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Andrea Kreienbühl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Emma Guttman-Yassky
- Department of Dermatology, and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alexandra F Santos
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St. Thomas' Hospital, London, UK
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Stefano Del Giacco
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | | | - David J Jackson
- Guy's Severe Asthma Centre, Guy's Hospital, Guy's & St Thomas' NHS Trust, London, UK
- School of Immunology & Microbial Sciences, King's College London, London, UK
| | - De-Yun Wang
- Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore City, Singapore
| | - Antti Lauerma
- Department of Dermatology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Heimo Breiteneder
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Liam O'Mahony
- Department of Medicine and School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Oliver Pfaar
- Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
| | - Robyn O'Hehir
- Allergy, Asthma & Clinical Immunology, The Alfred Hospital, Melbourne, Victoria, Australia
- Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Thomas Eiwegger
- Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria
- Department of Pediatric and Adolescent Medicine, University Hospital St. Pölten, St. Pölten, Austria
| | - Wytske J Fokkens
- Department of Otorhinolaryngology & Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Beatriz Cabanillas
- Department of Allergy, Instituto de Investigación Biosanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Cevdet Ozdemir
- Department of Pediatric Basic Sciences, Institute of Child Health, Istanbul University, Istanbul, Turkey
- Istanbul Faculty of Medicine, Department of Pediatrics, Division of Pediatric Allergy and Immunology, Istanbul University, Istanbul, Turkey
| | - Walter Kistler
- Department of Sports Medicine, Davos Hospital, Davos, Switzerland
- Swiss Research Institute for Sports Medicine (SRISM), Davos, Switzerland
- Medical Committee International Ice Hockey Federation (IIHF), Zurich, Switzerland
| | - Mahmut Bayik
- Department of Internal Medicine and Hematology, Marmara University, Istanbul, Turkey
| | - Kari C Nadeau
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Maria J Torres
- Allergy Unit, IBIMA-Hospital Regional Universitario de Málaga-ARADyAL, UMA, Málaga, Spain
| | - Mübeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Marek Jutel
- Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland
| | - Ioana Agache
- Faculty of Medicine, Department of Allergy and Clinical Immunology, Transylvania University, Brasov, Romania
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
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Lin W, Zou J, Di C, Rock CL, Natarajan L. Multilevel Longitudinal Functional Principal Component Model. Stat Med 2024; 43:4781-4795. [PMID: 39226919 PMCID: PMC12118512 DOI: 10.1002/sim.10207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 05/28/2024] [Accepted: 08/07/2024] [Indexed: 09/05/2024]
Abstract
Sensor devices, such as accelerometers, are widely used for measuring physical activity (PA). These devices provide outputs at fine granularity (e.g., 10-100 Hz or minute-level), which while providing rich data on activity patterns, also pose computational challenges with multilevel densely sampled data, resulting in PA records that are measured continuously across multiple days and visits. On the other hand, a scalar health outcome (e.g., BMI) is usually observed only at the individual or visit level. This leads to a discrepancy in numbers of nested levels between the predictors (PA) and outcomes, raising analytic challenges. To address this issue, we proposed a multilevel longitudinal functional principal component analysis (mLFPCA) model to directly model multilevel functional PA inputs in a longitudinal study, and then implemented a longitudinal functional principal component regression (FPCR) to explore the association between PA and obesity-related health outcomes. Additionally, we conducted a comprehensive simulation study to examine the impact of imbalanced multilevel data on both mLFPCA and FPCR performance and offer guidelines for selecting optimal methods.
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Affiliation(s)
- Wenyi Lin
- Division of Biostatistics, Herbert Wertheim School of Public Health and Longevity Science, University of California San Diego, La Jolla, California, USA
| | - Jingjing Zou
- Division of Biostatistics, Herbert Wertheim School of Public Health and Longevity Science, University of California San Diego, La Jolla, California, USA
| | - Chongzhi Di
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Cheryl L. Rock
- Division of Preventive Medicine, Department of Family Medicine, School of Medicine, University of California San Diego, La Jolla, California, USA
| | - Loki Natarajan
- Division of Biostatistics, Herbert Wertheim School of Public Health and Longevity Science, University of California San Diego, La Jolla, California, USA
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Bosch A, Rauh M, Striepe K, Schiffer M, Schmieder RE, Kannenkeril D. Renal adaptation in pre-obesity patients with hypertension. J Hypertens 2024; 42:1958-1965. [PMID: 39248112 DOI: 10.1097/hjh.0000000000003821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 07/09/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND AND HYPOTHESIS Obesity aggravates the risk to develop chronic kidney disease in hypertensive patients. Whether pre-obesity already impairs renal function, renal perfusion and intraglomerular hemodynamics in hypertensive patients is unknown. METHODS Renal hemodynamic profiles were measured using steady state input clearance (infusion of para-amino-hippuric acid and inulin) in 36 patients with primary arterial hypertension stage 1-2 without antihypertensive medication. Intraglomerular pressure (IGP) and resistances of the afferent (RA) and efferent (RE) arterioles were calculated. The study population was divided into two groups based on median of waist circumference (WC) (96 cm) (pre-obesity and non-obesity group1) and median of body mass index (BMI) (26.5 kg/m 2 ) (pre-obesity and non-obesity group2), respectively. RESULTS All patients were males, non-smoking, aged 36 ± 10 years, with an office blood pressure of 145 ± 8.6/89 ± 11.8 mmHg. None of the patients had cardiovascular disease. Patients from the pre-obese group 1 showed lower glomerular filtration rate (GFR), lower renal plasma flow (RPF) and lower IGP compared to the non-obese group1. Renal vascular resistance (RVR) and RA were higher in the pre-obese group1 compared to the non-obese group1. Similar differences in the hemodynamic profile were found for patients in the pre-obesity group2 compared to the non-obesity group2. CONCLUSION The renal hemodynamic profile in hypertensive patients with pre-obesity, irrespective whether defined by WC or BMI, was characterized by a reduced GFR and RPF and by an increased RVR preferentially at the preglomerular site. Our results suggest that hypofiltration is the first phase of renal adaptation in pre-obesity hypertension. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov : NCT02783456.
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Affiliation(s)
| | - Manfred Rauh
- Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), Erlangen, Germany
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Navarro González JF, Ortiz A, Cebrián Cuenca A, Moreno Barón M, Segú L, Pimentel B, Aranda U, Lopez-Chicheri B, Capel M, Pomares Mallol E, Caudron C, García Sánchez JJ, Alcázar Arroyo R. Projection of the clinical and economic burden of chronic kidney disease between 2022 and 2027 in Spain: Results of the Inside CKD project. Nefrologia 2024; 44:807-817. [PMID: 39632193 DOI: 10.1016/j.nefroe.2024.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 03/05/2024] [Accepted: 03/09/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND AND OBJECTIVE Chronic kidney disease (CKD) is a growing health problem affecting between 10% and 15% of the Spanish population. The lack of updated projections of the evolution of the disease burden hinders the development of evidence-based health policies and interventions to optimise the management of the disease and prevent its progression. The aim of this study is to project the evolution of the clinical and economic burden of CKD in Spain between 2022 and 2027. MATERIALS AND METHODS Inside CKD uses a validated microsimulation approach to project the burden of CKD. The projection is based on a virtual population according to Spanish demographics, literature, national data registries and clinical expert opinion. Costs associated with CKD management, renal replacement therapy (RRT), cardiovascular complications and arterial comorbidities were included. RESULTS In Spain, an absolute increase in the prevalence of CKD of 1% (from 10.7% to 11.7%) is expected between 2022 and 2027, corresponding to an increase from 5.14 million to 5.68 million patients in 2027. However, only one third of CKD patients would be diagnosed. Of these diagnosed patients, 3.9% will require RRT in 2027, an increase of 14.7% from 2022. A total of 654,281 accumulated deaths are expected in patients with CKD diagnosed between 2022 and 2027. The economic burden of diagnosed CKD is expected to increase by 13.8% to 4.89 billion euros in 2027, representing 5.56% of total Spanish public health expenditure in 2027 (compared to 4.88% in 2022), of which 42.5% will be allocated to RRT (2.4% of public health expenditure). CONCLUSIONS The Inside CKD project highlights the growing clinical, economic and social burden of CKD in Spain expected by 2027. Progression to more advanced stages with the need for RRT and associated complications represent a small proportion of the total CKD population, but contribute significantly to overall costs.
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Affiliation(s)
- Juan F Navarro González
- Unidad de Investigación y Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain; RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Tenerife, Spain; Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain
| | - Alberto Ortiz
- Servicio de Nefrología e Hipertensión, IIS-Fundación Jiménez Díaz UAM, Madrid, Spain
| | - Ana Cebrián Cuenca
- Medicina Familiar y Comunitaria, Centro de Salud Cartagena Casco Antiguo, Cartagena, Spain; Grupo de Atención Primaria del Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
| | - Marta Moreno Barón
- Asociación para la Lucha Contra las Enfermedades Renales (ALCER), Almería, Spain
| | - Lluís Segú
- Unidad de Farmacia Clínica y Farmacoterapia, Facultad de Farmacia, Universidad de Barcelona (UB), Barcelona, Spain; Acceso al Mercado, PharmaLex Spain, Barcelona, Spain
| | | | - Unai Aranda
- Global Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, United States
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Popa MM, Sirbu AE, Malinici EA, Copaescu C, Fica S. Obesity-related renal dysfunction: gender-specific influence of visceral adiposity and early impact of metabolic and bariatric surgery. Front Endocrinol (Lausanne) 2024; 15:1440250. [PMID: 39469576 PMCID: PMC11513314 DOI: 10.3389/fendo.2024.1440250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 09/25/2024] [Indexed: 10/30/2024] Open
Abstract
Introduction Renal dysfunction is a recognized complication of obesity with an incompletely characterized pathophysiology. Improvement of glomerular filtration rate (GFR) after metabolic and bariatric surgery (MBS) has been reported across all classes of renal function. Inter-gender differences with regard to correlates of renal function have been described, but the influence of body composition is an understudied area. We aimed to explore determinants of renal function in obesity and to assess its variations after MBS, with a focus on body composition parameters in males and females, respectively. Materials methods We conducted a retrospective study on 196 patients who underwent laparoscopic sleeve gastrectomy, evaluated preoperatively and 6 months after the intervention. Recorded data included clinical and biochemical assessment, as well as body composition estimation via dual-energy X-ray absorptiometry. Serum creatinine-based formulas were used for the estimation of GFR. Results We included a total of 196 patients (80 males and 116 females), with a mean age of 41.43 ± 10.79. Median baseline body mass index was 42.6 (6.61) kg/m2 and 6 months excess weight loss (EWL) reached 71.43 ± 17.18%, in females, estimated GFR correlated negatively with visceral adipose tissue (VAT) mass (rho=-.368) and this correlation was stronger in females with type 2 diabetes mellitus. Moreover, women in the third VAT mass tertile were 5 times more likely to have reduced GFR compared to the first tertile. Renal function improved after MBS across all classes of filtration. In males, this improvement correlated with EWL (rho=.358) and lean mass variation (rho=-.412), while in females it correlated with VAT mass variation (rho=-.266). Conclusions Our results are consistent with previous findings on the positive impact of MBS on renal function and suggest a more prominent impact of visceral adiposity on GFR in females.
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Affiliation(s)
- Miruna Maria Popa
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Endocrinology and Diabetes, Elias Emergency University Hospital, Bucharest, Romania
| | - Anca Elena Sirbu
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Endocrinology and Diabetes, Elias Emergency University Hospital, Bucharest, Romania
| | - Elisabeta Andreea Malinici
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Endocrinology and Diabetes, Elias Emergency University Hospital, Bucharest, Romania
| | - Catalin Copaescu
- General Surgery Department, Ponderas Hospital, Bucharest, Romania
| | - Simona Fica
- Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Endocrinology and Diabetes, Elias Emergency University Hospital, Bucharest, Romania
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Srivastava A, Nolan B, Jung JJ. Obesity: An Independent Predictor of Acute Renal Failure After General Surgery. Cureus 2024; 16:e71633. [PMID: 39553097 PMCID: PMC11566947 DOI: 10.7759/cureus.71633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2024] [Indexed: 11/19/2024] Open
Abstract
Background Half of Americans will have obesity, and a quarter will have severe obesity by the year 2030. Postoperative acute renal failure (ARF) is associated with increased morbidity and mortality. Given the increase in the number of patients with obesity undergoing elective surgery, we investigated the relationship between obesity and postoperative ARF after elective general surgery procedures. Methods We performed a retrospective cohort study of patients in the 2015-2019 National Surgical Quality Improvement Program database who underwent elective general surgery procedures. The primary outcome was the presence of postoperative ARF. The patient body mass index (BMI) was categorized as normal (BMI 18.5-24.9), overweight (BMI 25-29.9), obesity class 1 and 2 (BMI 30-39.9), severe obesity (BMI 40-49.9), and extreme obesity (BMI³50). Descriptive statistics and unadjusted comparisons were performed for patients who developed postoperative ARF and those who did not. Multivariable regression analyses were used to model BMI categories and postoperative ARF, adjusting for patient- and surgical-level covariates. Results Among 424,527 patients included in the study, 3638 patients (0.8%) developed ARF. Patients who developed ARF were older, had a higher BMI, and had more serious comorbidities. After risk adjustment, there was a stepwise rise in odds of developing postoperative ARF with increasing BMI categories compared to normal BMI: (overweight: OR 1.11 (95% CI 1.0-1.23), obesity class 1 and 2: OR 1.32 (95% CI 1.2-1.46), severe obesity: OR 1.45 (95% CI 1.27-1.66), and extreme obesity: OR 1.78 (95% CI 1.47-2.15)). Conclusion Obesity is independently associated with ARF after elective general surgery procedures.
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Affiliation(s)
- Ananya Srivastava
- Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, CAN
| | - Brodie Nolan
- Department of Emergency Medicine, St. Michael's Hospital, Toronto, CAN
| | - James J Jung
- Department of Surgery, Duke University, Durham, USA
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Kaneko T, Kodani E, Fujii H, Nakamura H, Sasabe H, Tamura Y. High body mass index and triglyceride levels at health checkups increase the risk of new-onset chronic kidney disease and worsening renal function: the TAMA MED Project-CKD. Clin Exp Nephrol 2024; 28:1016-1026. [PMID: 38767687 PMCID: PMC11493837 DOI: 10.1007/s10157-024-02507-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 04/24/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Health checkups are important in patients with chronic kidney disease (CKD), which is not easily accompanied by subjective symptoms. CKD can be caused or aggravated by factors that have not yet been identified. METHODS This retrospective cohort study included 7 483 patients who underwent specific annual health checkups at a medical institution in Tama City, did not have CKD in 2012, and continued to undergo checkups (aged 40-74 years). We examined the risk factors for new-onset CKD and 1.5-fold increase in serum creatinine levels among laboratory values from 2012 to 2020. RESULTS Age, body mass index (BMI), triglyceride levels, atrial fibrillation, and medication for hypertension (HT) and diabetes mellitus were independent risk factors for proteinuria, whereas current smoking, BMI, systolic blood pressure (SBP), and medication for HT were independent risk factors for estimated glomerular filtration rate < 60 mL/min/1.73 m2. SBP, triglyceride levels and medication for HT were risk factors for a 1.5-fold increase in serum creatinine levels during course of the study. The cut-off values of BMI for eGFR < 60 mL/min/1.73 m2 were 22.2 (men 24.7, women 22.1) kg/m2 and fasting triglyceride levels for a 1.5-fold increase in serum creatinine level were 171 (men 247, women 170) mg/dL, respectively. CONCLUSIONS Health checkups provide information to prevent new-onset CKD and worsening of renal function. It is necessary to increase the rate of health checkups and visits to medical institutions after health checkups as well as to use these results for health guidance.
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Affiliation(s)
- Tomohiro Kaneko
- Department of Nephrology, Nippon Medical School Tama-Nagayama Hospital, 1-7-1 Nagayama, Tama, Tokyo, 206-8512, Japan.
| | - Eitaro Kodani
- Department of Cardiovascular Medicine, Nippon Medical School Tama-Nagayama Hospital, 1-7-1 Nagayama, Tama, Tokyo, 206-8512, Japan
- TAMA CITY Medical Association, 5-15 Nagayama, Tama, Tokyo, 206-0025, Japan
| | - Hitomi Fujii
- TAMA CITY Medical Association, 5-15 Nagayama, Tama, Tokyo, 206-0025, Japan
- Tama-Center Mirai Clinic, 1-38 Ochiai, Tama, Tokyo, 206-0033, Japan
| | - Hiroyuki Nakamura
- TAMA CITY Medical Association, 5-15 Nagayama, Tama, Tokyo, 206-0025, Japan
| | - Hajime Sasabe
- TAMA CITY Medical Association, 5-15 Nagayama, Tama, Tokyo, 206-0025, Japan
| | - Yutaka Tamura
- TAMA CITY Medical Association, 5-15 Nagayama, Tama, Tokyo, 206-0025, Japan
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Higgins MS, Ismail S, Chen M, Agala CB, Detwiler R, Farrell TM, Hodges MM. Evaluating the safety of bariatric surgery as a bridge to kidney transplant: a retrospective cohort study. Surg Endosc 2024; 38:5980-5991. [PMID: 39085668 DOI: 10.1007/s00464-024-11087-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 07/13/2024] [Indexed: 08/02/2024]
Abstract
BACKGROUND Bariatric surgery has been proven safe in end-stage kidney disease (ESKD); however, few studies have evaluated whether a history of bariatric surgery impacts transplant-specific outcomes. We hypothesize that a history of bariatric surgery at the time of transplant does not adversely impact transplant-specific outcomes. METHODS The IBM MarketScan Commercial Claims and Encounters database was queried for patients with a history of kidney transplant between 2000 and 2021. Patients were stratified into three groups based on bariatric surgery status and body mass index (BMI) at the time of transplant: patients with obesity (O), patients without obesity (NO), and patients with a history of bariatric surgery (BS). Inverse probability of treatment weighting was used to control for confounding. Adjusted hazard ratios (aHRs) describing the risk of transplant-specific and postoperative outcomes were estimated using weighted Kaplan-Meier curves. Primary outcomes included 30-day and 1-year risk of transplant-specific outcomes. Secondary outcomes included 30-day and 1-year postoperative complications and 30-day and 1-year risk of wound-related complications. RESULTS We identified 14,806 patients; 128 in the BS group, 1572 in the O group, and 13,106 in the NO group. There was no difference in 30-day or 1-year risk of transplant-specific complications between the BS and NO group or the O and NO group. Patients with obesity (O) were more likely to experience wound infection (aHR 1.49, 95% CI 1.12-1.99), wound dehiscence (aHR 2.2, 95% CI 1.5-3.2), and minor reoperation (aHR 1.52, 95% CI 1.23-1.89) at 1 year. BS patients had increased risk of wound infection at 1 year (aHR 2.79, 95% CI 1.26-6.16), but were without increase in risk of minor or major reoperation. CONCLUSION A history of bariatric surgery does not adversely affect transplant-specific outcomes after kidney transplant. Bariatric surgery can be safely utilized to improve the transplant candidacy of patients with obesity with CKD and ESKD.
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Affiliation(s)
- Madeleine S Higgins
- Division of Gastrointestinal Surgery, Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, USA
| | - Sherin Ismail
- Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, USA
| | - Melissa Chen
- Division of Abdominal Transplantation, Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, USA
| | - Chris B Agala
- Division of Gastrointestinal Surgery, Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, USA
| | - Randal Detwiler
- Division of Nephrology and Hypertension, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, USA
| | - Timothy M Farrell
- Division of Gastrointestinal Surgery, Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, USA
| | - Maggie M Hodges
- Division of Gastrointestinal Surgery, Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, USA.
- Division of Gastrointestinal Surgery, Department of Surgery, The University of North Carolina at Chapel Hill, Burnett Womack Bldg, Suite 4034, 101 Manning Drive, Chapel Hill, NC, 27599-7081, USA.
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Han L, Chen X, Wan D, Xie M, Ouyang S. One anastomosis gastric bypass ameliorates diabetic nephropathy via regulating the GLP-1-mediated Sirt1/AMPK/PGC1α pathway. Clin Exp Nephrol 2024; 28:1051-1061. [PMID: 38782822 DOI: 10.1007/s10157-024-02516-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 05/13/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Diabetic nephropathy (DN), a complication of diabetes, is the most leading cause of end-stage renal disease. Bariatric surgery functions on the remission of diabetes and diabetes-related complications. One anastomosis gastric bypass (OAGB), one of popular bariatric surgery, can improve diabetes and its complications by regulating the glucagon-like peptide-1 (GLP-1) level. Meanwhile, GLP-1 can alleviate renal damage in high-fat-diet-induced obese rats. However, the effect of OAGB on renal injury remains uncertain in DN. METHODS A diabetes model was elicited in rats via HFD feeding and STZ injection. The role and mechanism of OAGB were addressed in DN rats by the body and kidney weight and blood glucose supervision, oral glucose tolerance test (OGTT), enzyme-linked immunosorbent assay (ELISA), biochemistry detection, histopathological analysis, and western blot assays. RESULTS OAGB surgery reversed the increase in body weight and glucose tolerance indicators in diabetes rats. Also, OAGB operation neutralized the DN-induced average kidney weight, kidney weight/body weight, and renal injury indexes accompanied with reduced glomerular hypertrophy, alleviated mesangial dilation and decreased tubular and periglomerular collagen deposition. In addition, OAGB introduction reduced the DN-induced renal triglyceride and renal cholesterol with the regulation of fatty acids-related proteins expression. Mechanically, OAGB administration rescued the DN-induced expression of Sirt1/AMPK/PGC1α pathway mediated by GLP-1. Pharmacological block of GLP-1 receptor inverted the effect of OAGB operation on body weight, glucose tolerance, renal tissue damage, and fibrosis and lipids accumulation in DN rats. CONCLUSION OAGB improved renal damage and fibrosis and lipids accumulation in DN rats by GLP-1-mediated Sirt1/AMPK/PGC1α pathway.
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Affiliation(s)
- Lang Han
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China
| | - Xiaojiao Chen
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China
| | - Dianwei Wan
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China
| | - Min Xie
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China
| | - Shurui Ouyang
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan, Zunyi, 563000, Guizhou, China.
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Ghazy F, Ebrahimi N, Ebadinejad A, Barzin M, Mahdavi M, Valizadeh M, Azizi F, Hosseinpanah F. Association of obesity severity and duration with incidence of chronic kidney disease. BMC Nephrol 2024; 25:320. [PMID: 39333911 PMCID: PMC11429187 DOI: 10.1186/s12882-024-03757-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
INTRODUCTION Obesity is a known risk factor for chronic kidney disease (CKD), but the impact of obesity severity and duration on CKD incidence is unclear. METHODS Cumulative Excess Weight (CEW) and Cumulative Excess Waist Circumference (CEWC) scores were calculated, which represent the accumulation of deviations from expected body mass index and waist circumference values over time until the development of CKD or the end of the follow-up period. Time-dependent Cox models were used to investigate the sex-stratified association of CEW and CEWC with CKD incidence while controlling for confounding variables. RESULTS Out of the 8697 participants who were evaluated in this study, 56% (4865) were women and the mean age was 40 ± 14. During the 15-year follow-up period, 41.7% (3629) of the participants developed CKD. Among the CKD patients, 65.4% (829) of men and 77.9% (1839) of women had a BMI higher than 25, and high WC was found to be 73.7% (934) and 55.3% (1306) for men and women, respectively. We found a significant association between one standard deviation change of CEW and the development of CKD in both sexes (fully adjusted hazard ratios and 95% CI of CEW in men and women were 1.155 [1.081-1.232) and 1.105 (1.047-1.167)]. However, the association between CEWC and CKD development was only significant among men participants [HR = 1.074 (1.006-1.147)]. CONCLUSION Over a 15-year follow-up, the accumulation of general and central obesity was associated with an increased incidence of CKD development.
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Affiliation(s)
- Faranak Ghazy
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-476, Tehran, Iran
| | - Navid Ebrahimi
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-476, Tehran, Iran
| | - Amir Ebadinejad
- Department of Surgery, Hartford Hospital/HealthCare, Hartford, CT, 06106, USA
| | - Maryam Barzin
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-476, Tehran, Iran
| | - Maryam Mahdavi
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-476, Tehran, Iran
| | - Majid Valizadeh
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-476, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farhad Hosseinpanah
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-476, Tehran, Iran.
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Ren L, Ju F, Liu S, Cai Y, Gang X, Wang G. New Perspectives on Obesity-Associated Nephropathy from Pathophysiology to Therapeutics: Revealing the Promise of GLP-1 RA Therapy. Drug Des Devel Ther 2024; 18:4257-4272. [PMID: 39347536 PMCID: PMC11437658 DOI: 10.2147/dddt.s476815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 09/10/2024] [Indexed: 10/01/2024] Open
Abstract
Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues.
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Affiliation(s)
- Linan Ren
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Feng Ju
- Department of Orthopedics, Yuci District People’s Hospital, Yuci, Shanxi, 030600, People’s Republic of China
| | - Siyuan Liu
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Yunjia Cai
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Xiaokun Gang
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Guixia Wang
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
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41
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Guldan M, Ozbek L, Topcu AU, Covic A, Kanbay M. Metabolically healthy obesity and chronic kidney disease risk: exploring the dynamics. Panminerva Med 2024; 66:293-308. [PMID: 38990212 DOI: 10.23736/s0031-0808.24.05112-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/12/2024]
Abstract
Obesity represents a prevalent global health concern with significant implications for various diseases, including chronic kidney disease (CKD). Within this landscape, the phenomenon of metabolically healthy obesity has emerged, challenging traditional notions about the health risks associated with excess weight. While traditional CKD risk factors involve obesity, metabolic syndrome, diabetes, and hypertension, the metabolically healthy obese (MHO) subgroup disrupts these assumptions. Our main objective in this study is to integrate existing literature on CKD in MHO individuals. In this endeavor, we delve into the pathophysiological foundations, the transition between obesity phenotypes and their impact on renal health, examine the implications of their metabolic resilience on mortality within a renal context, and explore potential management strategies specifically designed for MHO individuals. Offering a comprehensive overview of the pathophysiology, we cover various factors contributing to the risk of CKD in the metabolically healthy obese setting, including inflammation, cytokines, hemodynamics, and the renin-angiotensin-aldosterone system, gastrointestinal microbiota, diet, exercise, adipose distribution, and lipotoxicity. Through this synthesis, we aim to provide a comprehensive understanding of the risk of CKD in those classified as MHO.
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Affiliation(s)
| | - Lasin Ozbek
- School of Medicine, Koc University, Istanbul, Türkiye
| | - Ahmet U Topcu
- School of Medicine, Koc University, Istanbul, Türkiye
| | - Adrian Covic
- Department of Nephrology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, Iasi, Romania
| | - Mehmet Kanbay
- School of Medicine, Division of Nephrology, Department of Internal Medicine, Koç University, Istanbul, Türkiye -
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Yu L, Câmara NOS. The Impact of Obesity on Glomerular Diseases Remains to be Determined. Am J Kidney Dis 2024; 84:272-274. [PMID: 39023481 DOI: 10.1053/j.ajkd.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 06/08/2024] [Accepted: 06/23/2024] [Indexed: 07/20/2024]
Affiliation(s)
- Luis Yu
- Division of Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
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Culver SA, Hargett SR, Balugo JLLQ, Gildea JJ, Harris TE, Siragy HM. Nephron specific ATP6AP2 knockout increases urinary excretion of fatty acids and decreases renal cortical megalin expression. Sci Rep 2024; 14:18724. [PMID: 39134597 PMCID: PMC11319469 DOI: 10.1038/s41598-024-69749-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 08/08/2024] [Indexed: 08/15/2024] Open
Abstract
ATP6AP2 knockout in the renal nephron impairs receptor-mediated endocytosis, increasing urinary albumin and glucose excretion and impairing weight gain. Nonesterified fatty acids (NEFA) in urine are bound to albumin and reabsorbed in the proximal tubule through receptor-mediated endocytosis by the megalin-cubilin complex. We hypothesized that ATP6AP2 knockout increases urinary NEFA excretion through a reduction in megalin. Ten-week-old male C57BL/6 mice with nephron specific inducible ATP6AP2 knockout and noninduced controls were fed either normal diet (ND 12% fat) or high fat diet (HFD 45% fat) for 6 months. ATP6AP2 knockout significantly increased urine albumin:creatinine ratio in both ND and HFD fed mice while normalized urine NEFA concentration increased 489% and 259% in ND and HFD knockout mice compared to respective controls. Knockout decreased renal cortical megalin mRNA by 47% on ND and 49% on HFD while megalin protein expression decreased by 36% and 44% respectively. At the same time, markers of mTOR activity were increased while autophagy was impaired. Our results indicate that nephron specific ATP6AP2 knockout increases urinary NEFA excretion in the setting of impaired receptor-mediated endocytosis. Further investigation should determine whether ATP6AP2 contributes to obesity related ectopic lipid deposition in the proximal tubule.
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Affiliation(s)
- Silas A Culver
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, P.O. Box 801409, Charlottesville, VA, 22908-1409, USA.
| | - Stefan R Hargett
- Department of Pharmacology, University of Virginia Health System, Charlottesville, USA
| | - Jamie L L Q Balugo
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, P.O. Box 801409, Charlottesville, VA, 22908-1409, USA
| | - John J Gildea
- Department of Pathology, University of Virginia Health System, Charlottesville, USA
| | - Thurl E Harris
- Department of Pharmacology, University of Virginia Health System, Charlottesville, USA
| | - Helmy M Siragy
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, P.O. Box 801409, Charlottesville, VA, 22908-1409, USA
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Choi JY, Yang YM. Association between high-sensitivity C-reactive protein and renal function in Korean adults: A sex-specific analysis of Korea National Health and Nutrition Examination Survey 2015 to 2018 data. Medicine (Baltimore) 2024; 103:e38769. [PMID: 39093734 PMCID: PMC11296482 DOI: 10.1097/md.0000000000038769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 06/10/2024] [Indexed: 08/04/2024] Open
Abstract
This study aimed to investigate the association between high-sensitivity C-reactive protein (hs-CRP) levels, as a surrogate marker of systemic inflammation, and renal function among Korean adults grouped by age, sex, and body mass index. This study analyzed data obtained from the Korea National Health and Nutrition Examination Survey 2015 to 2018, a cross-sectional and nationally representative survey conducted by the Korean Centers for Disease Control and Prevention. Of the 22,451 subjects included in this study, 19,607 (87.3%) and 2844 (12.7%) had normal kidney function and incident chronic kidney disease, respectively. Reduced renal function was more frequently observed in subjects with high hs-CRP levels than in those with low hs-CRP levels (odds ratio [OR], 1.438; 95% confidence interval [CI], 1.234-1.674). In the group aged ≥ 65 years, the odds of reduced renal function were higher among subjects with a high hs-CRP level compared to those with a low hs-CRP level (OR, 1.528; 95% CI, 1.191-1.960). The association between hs-CRP level and renal function was observed only in women (OR, 2.485; 95% CI, 1.779-3.470) and further stratified by age and sex, the odds of reduced renal function were likely higher in women aged ≥ 65 years with a high hs-CRP level (OR, 2.338; 95% CI, 1.622-3.369). Moreover, reduced renal function was more observed in subjects aged ≥ 65 years and those with a body mass index < 25 kg/m2 (OR, 1.502; 95% CI, 1.087-2.075). This study showed that a high hs-CRP level likely contributes to the increased prevalence of reduced renal function. This association may aid the identification of individuals at high risk for reduced renal function, especially elderly women, in clinical or public health practice.
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Affiliation(s)
- Ji-Young Choi
- Department of Food and Nutrition, College of Natural Science and Public Health and Safety, Chosun University, Gwangju, Republic of Korea
| | - Young-Mo Yang
- Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, Republic of Korea
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Jakhotia S, Kavvuri R, Raviraj S, Baishya S, Pasupulati AK, Reddy GB. Obesity-related glomerulopathy is associated with elevated WT1 expression in podocytes. Int J Obes (Lond) 2024; 48:1080-1091. [PMID: 38504059 DOI: 10.1038/s41366-024-01509-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 02/26/2024] [Accepted: 03/01/2024] [Indexed: 03/21/2024]
Abstract
BACKGROUND The prevalence of obesity is increasing worldwide at an alarming rate. In addition to the increased incidence of cardiovascular and metabolic diseases, obesity is the most potent risk factor for developing chronic kidney disease (CKD). Although systemic events such as hemodynamic factors, metabolic effects, and lipotoxicity were implicated in the pathophysiology of obesity-related glomerulopathy (ORG) and kidney dysfunction, the precise mechanisms underlying the association between obesity and CKD remain unexplored. METHODS In this study, we employed spontaneous WNIN/Ob rats to investigate the molecular events that promote ORG. Further, we fed a high-fat diet to mice and analyzed the incidence of ORG. Kidney functional parameters, micro-anatomical manifestations, and podocyte morphology were investigated in both experimental animal models. Gene expression analysis in the rodents was compared with human subjects by data mining using Nephroseq and Kidney Precision Medicine Project database. RESULTS WNIN/Ob rats were presented with proteinuria and several glomerular deformities, such as adaptive glomerulosclerosis, decreased expression of podocyte-specific markers, and effacement of podocyte foot process. Similarly, high-fat-fed mice also showed glomerular injury and proteinuria. Both experimental animal models showed increased expression of podocyte-specific transcription factor WT1. The altered expression of putative targets of WT1 such as E-cadherin, podocin (reduced), and α-SMA (increased) suggests elevated expression of WT1 in podocytes elicits mesenchymal phenotype. Curated data from CKD patients revealed increased expression of WT1 in the podocytes and its precursors, parietal epithelial cells. CONCLUSION WT1 is crucial during nephron development and has minimal expression in adult podocytes. Our study discovered elevated expression of WT1 in podocytes in obesity settings. Our analysis suggests a novel function for WT1 in the pathogenesis of ORG; however, the precise mechanism of WT1 induction and its involvement in podocyte pathobiology needs further investigation.
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Affiliation(s)
- Sneha Jakhotia
- Department of Biochemistry, ICMR-National Institute of Nutrition, Hyderabad, 500007, TS, India
| | - Rajesh Kavvuri
- Department of Biochemistry, University of Hyderabad, Hyderabad, 500046, TS, India
| | - Sumathi Raviraj
- Department of Biochemistry, University of Hyderabad, Hyderabad, 500046, TS, India
| | - Somorita Baishya
- Department of Biochemistry, University of Hyderabad, Hyderabad, 500046, TS, India
| | | | - G Bhanuprakash Reddy
- Department of Biochemistry, ICMR-National Institute of Nutrition, Hyderabad, 500007, TS, India.
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Ihara Y, Sawa K, Imai T, Bito T, Shimomura Y, Kawai R, Shintani A. Immunotherapy and Overall Survival Among Patients With Advanced Non-Small Cell Lung Cancer and Obesity. JAMA Netw Open 2024; 7:e2425363. [PMID: 39093562 PMCID: PMC11297387 DOI: 10.1001/jamanetworkopen.2024.25363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/04/2024] [Indexed: 08/04/2024] Open
Abstract
IMPORTANCE The association between obesity and response to cancer treatment and survival remains unclear, with conflicting findings from various studies. The optimal choice between conventional chemotherapy and immunotherapy for first-line treatment remains uncertain in patients with obesity who potentially have an inadequate therapeutic response to immunotherapy. OBJECTIVE To investigate whether body mass index (BMI) modifies the association of immunotherapy or conventional therapy with overall survival in patients with advanced non-small cell lung cancer (aNSCLC). DESIGN, SETTING, and PARTICIPANTS A retrospective cohort study, using administrative claims data obtained from advanced treatment centers in Japan, was conducted between December 1, 2015, and January 31, 2023. Participants included individuals aged 18 years or older with aNSCLC who received immunotherapy, using immune checkpoint inhibitor (ICI) treatment or conventional chemotherapy. EXPOSURE Immune checkpoint inhibitor therapy as first-line chemotherapy was compared with conventional chemotherapy, identified through patient medical records. MAIN OUTCOMES AND MEASURES The main outcome was overall survival. Survival analysis covered a 3-year follow-up period after the first-line chemotherapy. RESULTS A total of 31 257 patients with aNSCLC were identified. Of these, 12 816 patients received ICI therapy (mean [SD] age, 70.2 [9.1] years; 10 287 [80.3%] men) and 18 441 patients received conventional chemotherapy (mean [SD] age, 70.2 [8.9] years; 14 139 [76.7%] men). Among patients with BMI less than 28, ICI therapy was associated with a significantly lower hazard of mortality (eg, BMI 24: hazard ratio [HR], 0.81; 95% CI, 0.75-0.87) compared with those who underwent conventional chemotherapy. However, no such association was observed among patients with BMI 28 or greater (eg, BMI 28: HR, 0.90; 95% CI, 0.81-1.00). CONCLUSIONS AND RELEVANCE The findings of this retrospective cohort study suggest that BMI modifies the association of ICI therapy compared with conventional chemotherapy with overall survival in patients with aNSCLC. A lack of association between ICI therapy and improved survival in patients with aNSCLC and overweight or obesity compared with conventional chemotherapy was observed. This suggests that ICI therapy may not be the optimal first-line therapy for patients with overweight or obesity and the use of conventional chemotherapy should also be considered in such patients.
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Affiliation(s)
- Yasutaka Ihara
- Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Kenji Sawa
- Department of Clinical Oncology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Takumi Imai
- Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Tsubasa Bito
- Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yuki Shimomura
- Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Ryota Kawai
- Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Ayumi Shintani
- Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
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47
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Stijven F, Alonso A, Molenberghs G. Proportion of treatment effect explained: An overview of interpretations. Stat Methods Med Res 2024; 33:1278-1296. [PMID: 39053571 DOI: 10.1177/09622802241259177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
The selection of the primary endpoint in a clinical trial plays a critical role in determining the trial's success. Ideally, the primary endpoint is the clinically most relevant outcome, also termed the true endpoint. However, practical considerations, like extended follow-up, may complicate this choice, prompting the proposal to replace the true endpoint with so-called surrogate endpoints. Evaluating the validity of these surrogate endpoints is crucial, and a popular evaluation framework is based on the proportion of treatment effect explained (PTE). While methodological advancements in this area have focused primarily on estimation methods, interpretation remains a challenge hindering the practical use of the PTE. We review various ways to interpret the PTE. These interpretations-two causal and one non-causal-reveal connections between the PTE principal surrogacy, causal mediation analysis, and the prediction of trial-level treatment effects. A common limitation across these interpretations is the reliance on unverifiable assumptions. As such, we argue that the PTE is only meaningful when researchers are willing to make very strong assumptions. These challenges are also illustrated in an analysis of three hypothetical vaccine trials.
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48
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Abi Mosleh K, Sample JW, Belluzzi A, Bartosiak K, Buttar D, Betancourt RS, Kukla A, Diwan TS, Ghanem OM. Bariatric surgery and the diseased kidney: a 5-year assessment of safety and postoperative renal outcomes. Surg Endosc 2024; 38:4014-4023. [PMID: 38872021 DOI: 10.1007/s00464-024-10983-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 06/02/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND Obesity and its related medical conditions are well-established contributors to the development of chronic kidney disease (CKD). Metabolic and bariatric surgery (MBS), including procedures such as sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), is a potential intervention for these individuals. However, the heightened risk of postoperative complications casts doubts on the suitability of MBS in this population. Our aim is to evaluate the long-term safety, anthropometric and renal outcomes of MBS in patients with CKD. METHODS A retrospective review of patients who underwent primary laparoscopic MBS with a BMI ≥ 35 kg/m2 and a preoperative diagnosis of stage 2 to 5 CKD. Criteria for CKD diagnosis and staging were based on estimated glomerular filtration rate measurements in accordance with established guidelines. Anthropometric and renal outcomes were measured at 3-, 6-, 12-, 24- and 60-months postoperatively. RESULTS A total of 302 patients (177 SG, 125 RYGB) were included. RYGB was preferred for patients with stage 3 CKD, while SG was more common in stages 4 and 5. At 5-year follow-up, percentage of total weight loss was higher in the RYGB cohort compared to SG (25.1% vs. 18.6%, p = 0.036). Despite SG patients having more advanced CKD, the incidence of late complications was significantly higher following RYGB, with 11 incidents (8.8%), compared to the SG cohort with only 4 cases (2.3%) (p = 0.014). In those with preoperative CKD stage 3, 76 patients (43.2%) improved to stage 2, with another 9 patients (5.1%) improving further to stage 1. Of all patients, 63 (20.8%) eventually received a successful renal transplant. CONCLUSIONS MBS is an effective strategy for sustained weight loss in patients with CKD with acceptable complications rates. RYGB leads to a higher percentage of overall weight loss, albeit with an elevated likelihood of late surgical complications. Future studies are needed to determine the safety of MBS in this demographic.
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Affiliation(s)
| | - Jack W Sample
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | | | | | | | | | - Aleksandra Kukla
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Tayyab S Diwan
- Department of Transplantation Surgery, Von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA
| | - Omar M Ghanem
- Department of Surgery, Mayo Clinic, Rochester, MN, USA.
- Division of Metabolic and Abdominal Wall Reconstructive Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
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Mao TH, Huang HQ, Zhang CH. Clinical characteristics and treatment compounds of obesity-related kidney injury. World J Diabetes 2024; 15:1091-1110. [PMID: 38983811 PMCID: PMC11229974 DOI: 10.4239/wjd.v15.i6.1091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 12/22/2023] [Accepted: 04/08/2024] [Indexed: 06/11/2024] Open
Abstract
Disorders in energy homeostasis can lead to various metabolic diseases, particularly obesity. The obesity epidemic has led to an increased incidence of obesity-related nephropathy (ORN), a distinct entity characterized by proteinuria, glomerulomegaly, progressive glomerulosclerosis, and renal function decline. Obesity and its associated renal damage are common in clinical practice, and their incidence is increasing and attracting great attention. There is a great need to identify safe and effective therapeutic modalities, and therapeutics using chemical compounds and natural products are receiving increasing attention. However, the summary is lacking about the specific effects and mechanisms of action of compounds in the treatment of ORN. In this review, we summarize the important clinical features and compound treatment strategies for obesity and obesity-induced kidney injury. We also summarize the pathologic and clinical features of ORN as well as its pathogenesis and potential therapeutics targeting renal inflammation, oxidative stress, insulin resistance, fibrosis, kidney lipid accumulation, and dysregulated autophagy. In addition, detailed information on natural and synthetic compounds used for the treatment of obesity-related kidney disease is summarized. The synthesis of detailed information aims to contribute to a deeper understanding of the clinical treatment modalities for obesity-related kidney diseases, fostering the anticipation of novel insights in this domain.
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Affiliation(s)
- Tuo-Hua Mao
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Han-Qi Huang
- Department of Endocrinology, Hubei No. 3 People’s Hospital of Jianghan University, Wuhan 430033, Hubei Province, China
| | - Chuan-Hai Zhang
- Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, United States
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50
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López-Martínez M, Armengol MP, Pey I, Farré X, Rodríguez-Martínez P, Ferrer M, Porrini E, Luis-Lima S, Díaz-Martín L, Rodríguez-Rodríguez AE, Cruz-Perera C, Alcalde M, Navarro-Díaz M. Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy. Int J Mol Sci 2024; 25:6437. [PMID: 38928144 PMCID: PMC11204096 DOI: 10.3390/ijms25126437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 06/02/2024] [Accepted: 06/08/2024] [Indexed: 06/28/2024] Open
Abstract
This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.
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Affiliation(s)
- Marina López-Martínez
- CSUR National Unit of Expertise for Complex Glomerular Diseases of Spain, Nephrology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Research, 08035 Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, 08913 Barcelona, Spain
| | - Maria Pilar Armengol
- Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, 08916 Barcelona, Spain
| | - Irina Pey
- Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, 08916 Barcelona, Spain
| | - Xavier Farré
- Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, 08916 Barcelona, Spain
| | | | - Mireia Ferrer
- Statistics and Bioinformatics Unit, Vall d’Hebron Research Institute, 08035 Barcelona, Spain
| | - Esteban Porrini
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Complejo Hospitalario Universitario de Canarias, 38320 La Laguna, Spain (L.D.-M.)
- Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, University of La Laguna, La Laguna, 38320 Tenerife, Spain
| | - Sergio Luis-Lima
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Complejo Hospitalario Universitario de Canarias, 38320 La Laguna, Spain (L.D.-M.)
- Department of Laboratory Medicine, Complejo Hospitalario Universitario de Canarias, La Laguna, 38320 Tenerife, Spain
| | - Laura Díaz-Martín
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Complejo Hospitalario Universitario de Canarias, 38320 La Laguna, Spain (L.D.-M.)
| | - Ana Elena Rodríguez-Rodríguez
- Research Unit, Hospital Universitario de Canarias, La Laguna, 38320 Tenerife, Spain
- Fundación General de la Universidad, University of La Laguna,38320 Tenerife, Spain
| | - Coriolano Cruz-Perera
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Complejo Hospitalario Universitario de Canarias, 38320 La Laguna, Spain (L.D.-M.)
| | - Marta Alcalde
- Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, 08916 Barcelona, Spain
- Pharmaco and Device Epidemiology Group, CSM, NDORMS, University of Oxford, Oxford OX1 3PT, UK
| | - Maruja Navarro-Díaz
- Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, 08916 Barcelona, Spain
- Nephrology Department, Sant Joan Despí Moisès Broggi Hospital, Sant Joan Despí, 08970 Barcelona, Spain
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