1
|
Zhao B, Zhang M, Liao S, Jiang T, Li J, Yang Z. Implication of serum soluble IL-2 receptor α in type 2 diabetes mellitus. J Diabetes Metab Disord 2025; 24:22. [PMID: 39712341 PMCID: PMC11659525 DOI: 10.1007/s40200-024-01536-x] [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: 07/16/2024] [Accepted: 10/01/2024] [Indexed: 12/24/2024]
Abstract
Objectives The aim of this study was to determine the association of serum soluble IL-2 receptor α (sIL-2RA) with T2DM-related characteristics and complications. Methods Serum sIL-2RA levels were determined in 156 T2DM patients, and the association with T2DM-related characteristics and complications was evaluated. Results Serum sIL-2RA levels were significantly increased in T2DM patients with diabetic kidney disease (DKD) (median, IQR, 1434.9, 958.1-1896.0, pg/ml), in comparison with those without DKD (median, IQR, 851.2, 660.2-1089.9, pg/ml)(P < 0.001). The ROC analysis revealed good performance of sIL-2RA for identifying DKD, with the areas under the curve of 0.789 (95%CI of 0.711-0.867, P < 0.001). The correlation analyses showed significantly positive correlations of serum sIL-2RA with urea (r = 0.458, P < 0.001), creatinine (r = 0.508, P < 0.001) and uACR (r = 0.469, P < 0.001), and negative correlation with eGFR (r=-0.561, P < 0.001). The multivariate analyses showed that serum sIL-2RA was independently associated with the increased risks of DKD (OR, 95%CI, 6.539, 1.401-30.529, P = 0.017) and DR (OR, 95%CI, 3.606, 1.073-12.114, P = 0.038). Additionally, serum sIL-2RA was significantly associated with inflammatory indicators in DKD patients, and with metablic indicators in non-DKD patients (all P < 0.05). Conclusion Serum sIL-2RA may be closely associated with inflammation, glucose and lipid metabolisms, DKD and DR risks in T2DM. Furthermore, it may be a potential biomarker for T2DM-related micro-vascular complications.
Collapse
Affiliation(s)
- Bing Zhao
- Department of Laboratory Medicine, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| | - Miaomiao Zhang
- Department of Laboratory Medicine, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| | - Shaoguang Liao
- Present Address: Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
- Department of Oncology, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| | - Tingwang Jiang
- Key Laboratory, Department of Science and Technology, The Second People’s Hospital of Changshu, The Affiliated Changshu Hospital of Xuzhou Medical University, Changshu, Jiangshu China
| | - Jie Li
- Department of Laboratory Medicine, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| | - Zaixing Yang
- Department of Laboratory Medicine, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| |
Collapse
|
2
|
Chafekar D. Optimizing chronic kidney disease management: The potential of a multi-strain probiotic formulation. World J Nephrol 2025; 14:101515. [DOI: 10.5527/wjn.v14.i1.101515] [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: 09/17/2024] [Revised: 10/21/2024] [Accepted: 12/03/2024] [Indexed: 01/20/2025] Open
Abstract
Chronic kidney disease (CKD), which represents a significant global health concern, is characterized by a gradual decline in kidney function, leading to complications such as electrolyte imbalance, cardiovascular disease, and immune dysfunction. Standard CKD management includes dietary modifications, ketoanalogues supplementation, blood pressure and blood glucose control, hydration maintenance, and treatment of the underlying causes. Emerging evidence has indicated a significant role of the gut microbiota in CKD, and that dysbiosis of the gut microbiota contributes to the progression of CKD towards end-stage renal disease. Probiotics and prebiotics have recently garnered attention owing to their potential to enhance gastrointestinal health and well-being by restoring the balance of the gut microbiota. Specific probiotic strains, including Lactobacillus and Bifidobacterium, promote beneficial bacterial growth, suppress harmful bacteria, and exert anti-inflammatory, antihypertensive, and antidiabetic effects. The combination of Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium longum, and Bacillus coagulans has demonstrated potential as a therapeutic formulation for CKD management in various studies, highlighting its promise in treating CKD; however, supporting evidence remains limited, making it crucial to conduct further investigations to determine the specific effects of different probiotic formulations on outcomes in patients with CKD.
Collapse
Affiliation(s)
- Deodatta Chafekar
- Dr V N Pawar Medical College, Director Supreme Kidney Care, Nashik 422005, Mahārāshtra, India
| |
Collapse
|
3
|
Srimongkhol P, Anutrakulchai S, Theeranut A, Methakanjanasak N, Lertsinudom S. Development of Chronic Kidney Disease Screening Integrative Care Model Led by Community Pharmacists. PHARMACY 2025; 13:27. [PMID: 39998025 PMCID: PMC11858870 DOI: 10.3390/pharmacy13010027] [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: 10/22/2024] [Revised: 01/31/2025] [Accepted: 02/11/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND The prevalence of chronic kidney disease (CKD) is rising, increasing demand for renal replacement therapy (RRT). Community pharmacies, as accessible healthcare hubs, can play a pivotal role in CKD prevention. This study aimed to develop care models for community pharmacies to optimize medication use, encourage behavior modification, and promote self-management among at-risk individuals. METHODS Conducted between June 2017 and July 2018, this study utilized an action research approach. Microalbuminuria was assessed using urine dipsticks, and pharmacists applied behavioral change and self-management support (SMS) strategies to slow CKD progression. Participants were categorized by albuminuria levels and enrolled in pharmacist-led care programs, with follow-up assessments at weeks 0 and 12. RESULTS Of 521 participants screened, 57% tested positive for albuminuria. For these individuals, serum creatinine testing and referrals to primary care were initiated. Self-management behavior assessment (S1) scores significantly improved (p = 0.024). Key factors associated with urine albumin levels included age < 60 years (OR = 0.44), diabetes (OR = 3.69), hypertension (OR = 2.01), BMI < 27.5 kg/m2 (OR = 0.42), eGFR ≥ 60 mL/min/1.73 m2 (OR = 3.34), lower systolic (OR = 0.55) and diastolic blood pressure (OR = 0.34), and fasting plasma glucose < 126 mg/dL (OR = 0.29). CONCLUSIONS Community pharmacist-led albuminuria screening effectively supports CKD prevention and enhances self-awareness within communities.
Collapse
Affiliation(s)
- Piangkwan Srimongkhol
- College of Pharmacotherapy Thailand, Nonthaburi 11000, Thailand
- Division of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Maha Sarakham 44150, Thailand
| | - Sirirat Anutrakulchai
- Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;
| | - Amponpun Theeranut
- Faculty of Nursing, Khon Kaen University, Khon Kaen 40002, Thailand; (A.T.); (N.M.)
| | | | - Sunee Lertsinudom
- Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| |
Collapse
|
4
|
Huang L, He L, Zeng Q, Huang J, Luo X, Zhong Q. Nonlinear association between glycated hemoglobin levels and mortality in elderly patients with non-diabetic chronic kidney disease: a national health and nutrition examination survey analysis. Front Endocrinol (Lausanne) 2025; 16:1416506. [PMID: 40007805 PMCID: PMC11850242 DOI: 10.3389/fendo.2025.1416506] [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: 04/12/2024] [Accepted: 01/22/2025] [Indexed: 02/27/2025] Open
Abstract
Background The relationship between glycated hemoglobin (HbA1c) levels and mortality outcomes in elderly patients with non-diabetic chronic kidney disease (CKD) has not been well characterized. This study aimed to investigate the correlation between HbA1c levels and all-cause and cardiovascular disease (CVD) mortality in elderly individuals with non-diabetic CKD. Methods Data from the NHANES (1999-2018) were analyzed to measure HbA1c levels in whole blood using high-performance liquid chromatography (HPLC). Information on deaths and subsequent details was collected through the National Mortality Index until December 31, 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for all-cause and CVD mortality were calculated using weighted Cox proportional hazards and restricted cubic spline models. Results Among the 1,931 participants (mean [SE] age, 73.2 [0.2] years; 61.9% female), over a median follow-up period of 7.6 years, a total of 1,003 deaths were observed, including 412 from CVD. HbA1c was divided into four quartiles: Quartile 1 (3.7-5.3%), Quartile 2 (5.4-5.6%), Quartile 3 (5.7-5.8%) as the reference group, and Quartile 4 (5.9-6.4%). Higher risks of all-cause mortality were noted in the lowest and highest HbA1c quartiles, with adjusted HR (95% CI) of 1.48 (1.18-1.87) and 1.31 (1.01-1.70) respectively. For CVD mortality, the lowest quartile showed a significantly increased risk (HR 1.94, 95% CI: 1.29-2.90), but the highest quartile did not significantly differ from the reference, with HR 1.14 (0.73-1.77). The RCS analysis indicated a U-shaped nonlinear relationship between HbA1c levels and all-cause mortality (P = 0.026 for nonlinearity) and a J-shaped nonlinear relationship with CVD mortality (P = 0.035 for nonlinearity). Conclusion This cohort study suggests that both low and high HbA1c levels are associated with an increased risk of all-cause mortality in elderly patients with non-diabetic CKD.
Collapse
Affiliation(s)
- Lihua Huang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Liuliu He
- Department of Clinical Laboratory, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Qingfeng Zeng
- Department of Neurology, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jinjing Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Xiaoyan Luo
- Department of Interventional Radiology, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Qiuming Zhong
- Department of Hospital Pharmacy, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, China
| |
Collapse
|
5
|
Vernaza Trujillo DA, Rojas Bautista LY, Ramirez Espinosa CM, Sierra Castillo S, Corredor-Rengifo D, Aristizabal Colorado D, Abreu Lomba A. Impact of SGLT2 Inhibitors on Preventing Heart Failure Hospitalizations in Colombian Patients With Uncontrolled Type 2 Diabetes Mellitus. Cureus 2025; 17:e77725. [PMID: 39974248 PMCID: PMC11839060 DOI: 10.7759/cureus.77725] [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: 01/19/2025] [Indexed: 02/21/2025] Open
Abstract
OBJECTIVE This study aims to evaluate the effects of SGLT2 inhibitors, specifically empagliflozin and dapagliflozin, on the prevention of heart failure hospitalizations and the improvement of metabolic control in patients with type 2 diabetes mellitus (T2DM) without documented high cardiovascular risk. The study aimed to assess the impact of these treatments on glycemic control, blood pressure, weight, and cardiovascular outcomes over an 18-month follow-up period in a Colombian population. MATERIALS AND METHODS A retrospective cohort study was conducted with 122 patients with uncontrolled T2DM at the Clínica Imbanaco in Cali, Colombia. Five treatment groups were identified, including various metformin combinations with other agents intensified with empagliflozin and dapagliflozin. Patients were retrospectively followed for 18 months, assessing treatment effects on the first hospitalization due to heart failure, glycemic control, blood pressure, and body weight. Multivariate repeated-measures ANOVA was used to analyze clinical variable changes over time. Additionally, Kaplan-Meier survival analysis estimated the cumulative probability of hospitalization for each treatment group, and Cox regression evaluated associations between different treatments and the risk of heart failure hospitalization. RESULTS Patients treated with metformin + empagliflozin showed a significant reduction in HbA1c levels, from an initial mean of 7.75% to 6.77% at the end of follow-up (-0.97%; 95% CI: -1.31 to -0.63, p < 0.001) compared to baseline. Blood pressure in the empagliflozin group also showed significant decreases. Final systolic blood pressure reached an average of 120.40 mmHg (95% CI: -22.63 to 1.54, p > 0.05), reflecting a -10.55 mmHg reduction from baseline. Diastolic blood pressure decreased to an average of 78 mmHg (95% CI: -10.71 to -0.69, p < 0.05), with a reduction of -5.7 mmHg compared to baseline. Regarding hospitalizations, Cox regression analysis indicated an HR of 0 for the empagliflozin group (p < 0.001), with no reported heart failure hospitalizations during the study period. CONCLUSIONS Analysis of left ventricular ejection fraction and first heart failure hospitalization in patients with T2DM treated with SGLT2 inhibitors reveals that empagliflozin is not only effective in glycemic control, weight management, and blood pressure reduction but also shows preventive potential against heart failure progression, even in patients without high cardiovascular risk. These findings, aligned with evidence from classical studies, suggest that empagliflozin should be considered in the early management of T2DM to reduce heart failure incidence and improve long-term outcomes.
Collapse
Affiliation(s)
- David Alexander Vernaza Trujillo
- Epidemiology, Fundación Universitaria del Área Andina, Bogotá, COL
- Interinstitutional Group of Internal Medicine 1 (GIMI1), Universidad Libre, Cali, COL
| | | | | | | | - David Corredor-Rengifo
- Interinstitutional Group of Internal Medicine 1 (GIMI1), Universidad Libre, Cali, COL
- Internal Medicine, Universidad Libre, Cali, COL
| | | | | |
Collapse
|
6
|
ElSayed NA, McCoy RG, Aleppo G, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Echouffo-Tcheugui JB, Ekhlaspour L, Garg R, Khunti K, Lal R, Lingvay I, Matfin G, Pandya N, Pekas EJ, Pilla SJ, Polsky S, Segal AR, Seley JJ, Stanton RC, Bannuru RR. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S239-S251. [PMID: 39651975 PMCID: PMC11635029 DOI: 10.2337/dc25-s011] [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] [Indexed: 12/14/2024]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Collapse
|
7
|
De Cosmo S, Pontremoli R, Giandalia A, Manicardi V, Rocca A, Nicolucci A, Rossi MC, Lucisano G, Graziano G, Di Bartolo P, Di Cianni G, Candido R, Russo GT. Generalizability of kidney and cardiovascular protection by finerenone to the real world in Italy: insights from Fidelio and Figaro studies. J Nephrol 2024:10.1007/s40620-024-02171-8. [PMID: 39676127 DOI: 10.1007/s40620-024-02171-8] [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: 06/03/2024] [Accepted: 11/16/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND We evaluated the proportion of Type 2 diabetes (T2D) patients with chronic kidney disease (CKD) participating in the AMD (Association of Medical Diabetologists) Annals initiative who met the eligibility criteria for phase III-studies on finerenone, showing its renal and cardiovascular benefits. METHODS This analysis involved all T2D patients seen in 2019 in 282 diabetes centers in Italy, for whom data on kidney function (estimated glomerular filtration rate and albuminuria) were available. Data are presented separately for different scenarios, covering the population with main eligibility criteria for inclusion in the FIDELIO-DKD and FIGARO-DKD trials. RESULTS Among 343,037 T2D patients involved in the analysis, 5.4% met the eligibility criteria of the FIDELIO-DKD study (13.3% if we consider the population with fundus data) and 22.3% met those of the FIGARO-DKD trial. Overall, 110,000 (33%) patients were eligible for treatment with finerenone, with a male prevalence, an average age of 71 years, and good control of the main risk factors (HbA1c 7.3%; BP 138/76 mmHg; LDL-c 87 mg/dl), albeit with large percentages of not well controlled patients (50% with SBP > 140 mmHg; > 30% with LDL-c > 100 mg/dl). Over 12% were on sodium/glucose cotransporter 2 inhibitors or glucagon-like peptide 1 receptor agonists. Based on the event rate from the FIDELITY pooled analysis, the number of potentially avoidable events was 21.7 per 1000 eligible patients for the cardiovascular composite outcome and 16.7 for the renal outcome. CONCLUSIONS This analysis showed that approximately 33% of patients with T2D present the main eligibility criteria for treatment with finerenone and could therefore benefit from it in the near future.
Collapse
Affiliation(s)
- Salvatore De Cosmo
- Department of Medical Sciences, Scientific Institute "Casa Sollievo Della Sofferenza", San Giovanni Rotondo, FG, Italy
| | - Roberto Pontremoli
- Department of Internal Medicine, University of Genoa and I.R.C.C.S., Viale Benedetto XV, 16125, Genoa, Italy
| | - Annalisa Giandalia
- Department of Human Pathology of Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy.
| | | | - Alberto Rocca
- "G. Segalini" H. Bassini Cinisello Balsamo ASST Nord, Milan, Italy
| | - Antonio Nicolucci
- CORESEARCH - Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy
| | - Maria Chiara Rossi
- CORESEARCH - Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy
| | - Giuseppe Lucisano
- CORESEARCH - Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy
| | - Giusi Graziano
- CORESEARCH - Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy
| | - Paolo Di Bartolo
- Department of Specialist Medicine, Ravenna Diabetes Center, Romagna Local Health Authority, Ravenna, Italy
| | - Graziano Di Cianni
- Diabetes and Metabolic Diseases Unit, Health Local Unit North-West Tuscany, Leghorn, Italy
| | - Riccardo Candido
- Diabetes Centre, University of Trieste, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
| | - Giuseppina T Russo
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| |
Collapse
|
8
|
Cheng Y, Liu Y, Lin L, Li D, Peng L, Zheng K, Tao J, Li M. The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study. Ren Fail 2024; 46:2295425. [PMID: 38178377 PMCID: PMC10773657 DOI: 10.1080/0886022x.2023.2295425] [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: 03/28/2023] [Accepted: 12/11/2023] [Indexed: 01/06/2024] Open
Abstract
AIM Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. METHODS Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. RESULTS By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). CONCLUSION In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.
Collapse
Affiliation(s)
- Yaqi Cheng
- Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Yuhao Liu
- Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Liling Lin
- Department of Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Danni Li
- Department of Emergency, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liying Peng
- Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Ke Zheng
- Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Jianling Tao
- Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Mingxi Li
- Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| |
Collapse
|
9
|
Fu Z, Geng X, Liu C, Shen W, Dong Z, Sun G, Cai G, Chen X, Hong Q. Identification of common and specific fibrosis-related genes in three common chronic kidney diseases. Ren Fail 2024; 46:2295431. [PMID: 38174742 PMCID: PMC10769532 DOI: 10.1080/0886022x.2023.2295431] [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: 12/11/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND Kidney fibrosis is the common final pathway of virtually all advanced forms of chronic kidney disease (CKD) including diabetic nephropathy (DN), IgA nephropathy (IgAN) and membranous nephropathy (MN), with complex mechanism. Comparative gene expression analysis among these types of CKD may shed light on its pathogenesis. Therefore, we conducted this study aiming at exploring the common and specific fibrosis-related genes involved in different types of CKD. METHODS Kidney biopsy specimens from patients with different types of CKD and normal control subjects were analyzed using the NanoString nCounter® Human Fibrosis V2 Panel. Genes differentially expressed in all fibrotic DN, IgAN and MN tissues compared to the normal controls were regarded as the common fibrosis-related genes in CKD, whereas genes exclusively differentially expressed in fibrotic DN, IgAN or MN samples were considered to be the specific genes related to fibrosis in DN, IgAN and MN respectively. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of the selected genes. RESULTS Protein tyrosine phosphatase receptor type C (PTPRC), intercellular cell adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), interleukin 10 receptor alpha (IL10RA) and CC chemokine receptor 2 (CCR2) were identified as the potential common genes for kidney fibrosis in different types of CKD, while peroxisome proliferator-activated receptor alpha (PPARA), lactate oxidase (LOX), secreted phosphoprotein 1 (SPP1) were identified as the specific fibrosis-associated genes for DN, IgAN and MN respectively. qRT-PCR demonstrated that the expression levels of these selected genes were consistent with the NanoString analysis. CONCLUSIONS There were both commonalities and differences in the mechanisms of fibrosis in different types of CKD, the commonalities might be used as the common therapeutic targets for kidney fibrosis in CKD, while the differences might be used as the diagnostic markers for DN, IgAN and MN respectively. Inflammation was highly relevant to the pathogenesis of fibrosis. This study provides further insight into the pathophysiology and treatment of fibrotic kidney disease.
Collapse
Affiliation(s)
- Zhangning Fu
- Medical School of Chinese PLA, Beijing, China
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Xiaodong Geng
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Chao Liu
- Department of Critical Care Medicine, First Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Wanjun Shen
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Zheyi Dong
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Guannan Sun
- Medical School of Chinese PLA, Beijing, China
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Guangyan Cai
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Xiangmei Chen
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Quan Hong
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| |
Collapse
|
10
|
Li XQ, Xiao ZZ, Ma K, Liu XY, Liu HH, Hu B, Zhao Q, Li HY, Chen RC, Meng Y, Yin LH. Angiotensin-Converting Enzyme-Dependent Intrarenal Angiotensin II Contributes to CTP: Phosphoethanolamine Cytidylyltransferase Downregulation, Mitochondrial Membranous Disruption, and Reactive Oxygen Species Overgeneration in Diabetic Tubulopathy. Antioxid Redox Signal 2024. [PMID: 39495586 DOI: 10.1089/ars.2024.0637] [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: 11/06/2024]
Abstract
Aims: The limited therapeutic options for diabetic tubulopathy (DT) in early diabetic kidney disease (DKD) reflect the difficulty of targeting renal tubular compartment. While renin-angiotensin-aldosterone system (RAS) inhibitors are commonly utilized in the management of DKD, how intrarenal RAS contributes to diabetic tubular injury is not fully understood. Mitochondrial disruption and reactive oxygen species (ROS) overgeneration have been involved in diabetic tubular injury. Herein, we aim to test the hypothesis that angiotensin-converting enzyme (ACE)-dependent intrarenal angiotensin II (AngII) disrupts tubular mitochondrial membranous homeostasis and causes excessive ROS generation in DT. Results: Mice suffered from renal tubular mitochondrial disruption and ROS overgeneration following high-fat diet/streptozocin-type 2 diabetic induction. Intrarenal AngII generation is ACE-dependent in DT. Local AngII accumulation in renal tissues was achieved by intrarenal artery injection. ACE-dependent intrarenal AngII-treated mice exhibit markedly elevated levels of makers of tubular injury. CTP: Phosphoethanolamine cytidylyltransferase (PCYT2), the primary regulatory enzyme for the biosynthesis of phosphatidylethanolamine, was enriched in renal tubules according to single-cell RNA sequencing. ACE-dependent intrarenal AngII-induced tubular membranous disruption, ROS overgeneration, and PCYT2 downregulation. The diabetic ambiance deteriorated the detrimental effect of ACE-dependent intrarenal AngII on renal tubules. Captopril, the ACE inhibitor (ACEI), showed efficiency in partially ameliorating ACE-dependent intrarenal AngII-induced tubular deterioration pre- and post-diabetic induction. Innovation and Conclusion: This study uncovers a critical role of ACE-dependent intrarenal AngII in mitochondrial membranous disruption, ROS overgeneration, and PCYT2 deficiency in diabetic renal tubules, providing novel insight into DT pathogenesis and ACEI-combined therapeutic targets. Antioxid. Redox Signal. 00, 000-000.
Collapse
Affiliation(s)
- Xia-Qing Li
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Nephrology Department, The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, China
| | - Zhang-Zhang Xiao
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Nephrology Department, Houjie Hospital of Dongguan, Dongguan, China
| | - Ke Ma
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Nephrology Department, The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, China
| | - Xia-Yun Liu
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Nephrology Department, The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, China
| | - Huan-Huan Liu
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Bo Hu
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Qian Zhao
- Department of Infectious Diseases and Hepatology Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hong-Yue Li
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Nephrology Department, The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, China
| | - Rui-Chang Chen
- Department of Emergency Medicine, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Yu Meng
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Nephrology Department, The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, China
- Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, China
| | - Liang-Hong Yin
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Huangpu Institute of Materials, Guangzhou, China
| |
Collapse
|
11
|
Aristizábal-Colorado D, Ocampo-Posada M, Rivera-Martínez WA, Corredor-Rengifo D, Rico-Fontalvo J, Gómez-Mesa JE, Duque-Ossman JJ, Abreu-Lomba A. SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art. Am J Cardiovasc Drugs 2024; 24:707-718. [PMID: 39179723 DOI: 10.1007/s40256-024-00673-1] [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] [Accepted: 08/06/2024] [Indexed: 08/26/2024]
Abstract
Type 2 diabetes mellitus (T2DM) is associated with a heightened risk of cardiovascular and renal complications. While glycemic control remains essential, newer therapeutic options, such as SGLT2 inhibitors, offer additional benefits beyond glucose reduction. This review delves into the mechanisms underlying the cardio-renal protective effects of SGLT2 inhibitors. By inducing relative hypoglycemia, these agents promote ketogenesis, optimize myocardial energy metabolism, and reduce lipotoxicity. Additionally, SGLT2 inhibitors exert renoprotective actions by enhancing renal perfusion, attenuating inflammation, and improving iron metabolism. These pleiotropic effects, including modulation of blood pressure, reduction of uric acid, and improved endothelial function, collectively contribute to the cardiovascular and renal benefits observed with SGLT2 inhibitor therapy. This review will provide clinicians with essential knowledge, understanding, and a clear recollection of this pharmacological group's mechanism of action.
Collapse
Affiliation(s)
- David Aristizábal-Colorado
- Department of Internal Medicine, Universidad Libre, Cali, Colombia
- Internal Medicine Research Group, Universidad Libre, Cali, Colombia
- Interamerican Society of Cardiology (SIAC), Mexico City, Mexico
| | - Martín Ocampo-Posada
- Department of Internal Medicine, Universidad Libre, Cali, Colombia
- Internal Medicine Research Group, Universidad Libre, Cali, Colombia
- Faculty of Health, Pontificia Universidad Javeriana, Cali, Colombia
- Grupo de Investigación en Ciencias Básicas y Clínicas de la Salud, Universidad Javeriana, Cali, Colombia
| | - Wilfredo Antonio Rivera-Martínez
- Internal Medicine Research Group, Universidad Libre, Cali, Colombia
- Department of Endocrinology, Faculty of Medicine, Universidad de Antioquia, Medellin, Colombia
| | - David Corredor-Rengifo
- Department of Internal Medicine, Universidad Libre, Cali, Colombia
- Internal Medicine Research Group, Universidad Libre, Cali, Colombia
| | - Jorge Rico-Fontalvo
- Department of Nephrology. Faculty of Medicine, Universidad Simón Bolívar, Barranquilla, Colombia
- Latin American Society of Nephrology and Arterial Hypertension (SLANH), Panama City, Panamá
| | - Juan Esteban Gómez-Mesa
- Interamerican Society of Cardiology (SIAC), Mexico City, Mexico.
- Cardiology Department, Fundación Valle del Lili, Cali, Colombia.
- Department of Health Sciences, Universidad Icesi, Cali, Colombia.
| | - John Jairo Duque-Ossman
- Universidad Del Quindío, Armenia, Colombia
- Latin American Federation of Endocrinology (FELAEN), Armenia, Colombia
| | - Alin Abreu-Lomba
- Internal Medicine Research Group, Universidad Libre, Cali, Colombia
- Endocrinology Department, Clínica Imbanaco, Cali, Colombia
| |
Collapse
|
12
|
Ness BM, Webb H. Finerenone: Who should prescribe it for CKD? The physician associate's perspective. J Nephrol 2024; 37:2161-2170. [PMID: 38958872 PMCID: PMC11649777 DOI: 10.1007/s40620-024-02015-5] [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: 03/14/2024] [Accepted: 06/15/2024] [Indexed: 07/04/2024]
Abstract
Diabetic kidney disease (DKD) affects 30-40% of all patients with diabetes and contributes significantly to the cardiovascular burden of chronic kidney disease (CKD). Despite the availability of evidence-based medications like finerenone and simple screening tests such as Urinary Albumin-to-Creatinine Ratio (UACR), more resources are still needed to care for DKD patients. Physician Associates (PAs) play a crucial role in the multidisciplinary team responsible for DKD diagnosis, monitoring, and management. A nonsteroidal mineralocorticoid receptor antagonist, namely finerenone, was approved by the FDA in adults with CKD associated with type 2 diabetes to reduce the risk of renal and cardiovascular outcomes. Finerenone is considered among the pillars of care for DKD, furthermore, the addition of finerenone in combination with renin-angiotensin system inhibitors and/or other renal protective medications may offer additional benefits. Primary care providers prescribe finerenone less frequently than specialized care providers, indicating a need to empower physician associates in medication prescription and other renal protection strategies. As part of a multidisciplinary team, physician associates can play an important role in evaluating risk factors that contribute to heart disease and metabolic health. They can also monitor not only kidney function by ordering tests, such as serum creatinine and urinary albumin-to-creatinine ratio every 3-12 months, but also serum potassium levels. Additionally, physician associates can encourage patients to take responsibility for their health by regularly monitoring their blood pressure, blood glucose levels, and body weight. With early detection and management, kidney failure and cardiovascular events may be preventable. Specialized physician associates also play a significant role in the comprehensive care of DKD patients, especially in the later stages. DKD care can be hindered by numerous factors such as lack of patient engagement during counseling, cost disparities, and a complex referral system that requires multidisciplinary guidelines to improve professional communication. It is necessary to re-envision the physician associates' role in primary care and empower them in goal-directed therapies.
Collapse
Affiliation(s)
- Becky M Ness
- Department of Nephrology, Mayo Clinic College of Medicine, Rochester, MN, USA.
| | - Heidi Webb
- Bahl & Bahl Medical Associates, Pittsburgh, PA, USA
| |
Collapse
|
13
|
Jung I, Nam S, Lee DY, Park SY, Yu JH, Seo JA, Lee DH, Kim NH. Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus. Diabetes Metab J 2024; 48:1126-1134. [PMID: 38945526 PMCID: PMC11621657 DOI: 10.4093/dmj.2023.0377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 05/06/2024] [Indexed: 07/02/2024] Open
Abstract
BACKGRUOUND Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD. METHODS We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573). RESULTS Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria. CONCLUSION Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.
Collapse
Affiliation(s)
- Inha Jung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seungyoon Nam
- Department of Genome Medicine and Science, AI Convergence Center for Medical Science, Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon, Korea
| | - Da Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - So Young Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hee Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Dae Ho Lee
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon, Korea
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| |
Collapse
|
14
|
Pratama D, Wasisto O, Kekalih A, Suhartono R, Muradi A, Ferian MF, Akbar A. The relationship between post-anastomosis brachial artery flow rate and brachiocephalic arteriovenous fistula access maturity in end-stage kidney disease patients with diabetes mellitus. ULTRASOUND (LEEDS, ENGLAND) 2024:1742271X241287926. [PMID: 39555160 PMCID: PMC11563531 DOI: 10.1177/1742271x241287926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 09/12/2024] [Indexed: 11/19/2024]
Abstract
Background From previous studies, evaluation of post-anastomosis draining-vein volume flow rate with Doppler ultrasound can be a predictor for arteriovenous fistula maturation. Due to the high variation in measurements by the effect of probe pressure in draining vein, measuring volume flow rate based on post-anastomosis feeding-artery may be an early alternative predictor of arteriovenous fistula maturation. This study aims to investigate the correlation of post-creation brachial artery volume flow rate on maturity of brachiocephalic arteriovenous fistula access in patients with end-stage kidney disease with diabetes mellitus. Methods A retrospective cohort study was conducted on end-stage kidney disease patients with diabetes mellitus who underwent brachiocephalic arteriovenous fistula creation at three hospitals from July 2019 to March 2020. Doppler ultrasound examination of the brachial artery and draining vein volume flow rate was conducted at pre-operative, post-creation, 2 weeks, and 6 weeks post-creation. Maturity was evaluated at 6 weeks post-anastomosis. Results A total of 71 subjects met the inclusion and exclusion criteria, with 44 (62%) achieving maturation within 6 weeks. There was a correlation between post-anastomosis brachial artery (p < 0.001) and draining vein volume flow rate (p < 0.001) with arteriovenous fistula maturity after 6 weeks post-operatively. Brachial artery volume flow rate of ⩾350 mL/min can predict AVF maturity with a sensitivity of 95.45% (95% confidence interval = 84.86-98.74) and a specificity of 85.19% (95% confidence interval = 67.52-94.08). Conclusion Post-anastomosis brachial artery flow volume can be a valuable parameter to predict brachiocephalic arteriovenous fistula maturity. It is a potential alternative to draining vein volume flow, which is technically a difficult examination.
Collapse
Affiliation(s)
- Dedy Pratama
- Division of Vascular and Endovascular Surgery, Department of Surgery, Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Octavianus Wasisto
- Division of Vascular and Endovascular Surgery, Department of Surgery, Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Aria Kekalih
- Department of Community Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Raden Suhartono
- Division of Vascular and Endovascular Surgery, Department of Surgery, Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Akhmadu Muradi
- Division of Vascular and Endovascular Surgery, Department of Surgery, Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Muhammad F Ferian
- Division of Vascular and Endovascular Surgery, Department of Surgery, Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Avicenna Akbar
- Division of Vascular and Endovascular Surgery, Department of Surgery, Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| |
Collapse
|
15
|
Cai J, Song L, Hu Z, Gao X, Wang Y, Chen Y, Xi K, Lu X, Shi Y. Astragalin alleviates oligoasthenospermia via promoting nuclear translocation of Nrf2 and reducing ferroptosis of testis. Heliyon 2024; 10:e38778. [PMID: 39444397 PMCID: PMC11497445 DOI: 10.1016/j.heliyon.2024.e38778] [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: 01/29/2024] [Revised: 09/27/2024] [Accepted: 09/30/2024] [Indexed: 10/25/2024] Open
Abstract
Oligoasthenospermia (OAS) is a global human developmental disease and the most common type of male infertility. There are currently no sufficiently effective therapeutic strategies for OAS. Wuziyanzong Pill (WZYZP) is a traditional Chinese prescription for the clinical treatment of male infertility, and its efficacy is well known in China. Therefore, due to the complexity of traditional Chinese medicine, the specific mechanism of action of WZYZP on OAS has not been elucidated. Astragalin (AG), one of the main active substances in WZYZP, has good antioxidant effect. The aim of this research is to investigate whether AG, the active substance in WZYZP, can treat OAS by promoting Nrf2 nuclear translocation and inhibiting ferroptosis. The OAS model was established by intraperitoneal injection of cyclophosphamide, and the therapeutic effects of AG and WZYZP on OAS were evaluated by detecting sperm quality, sex hormone levels and testicular pathological changes after intragastric administration of AG and WZYZP. Western blot was used to measure the expression levels of TFR1, SLC7A11, GPX4 and FTH1. The nuclear translocation of Nrf2 was detected by immunofluorescence staining and nuclear/intracellular expression of Nrf2. The results showed that AG could improve sperm quality and serum sex hormone levels in OAS rats, reduce the expression of testicular Fe2+ and TFR1, up-regulate testicular SLC7A11, GPX4 and FTH1, and inhibit testicular ferroptosis. At the same time, AG can promote the expression and nuclear translocation of Nrf2 in the testis of OAS rats. AG can alleviate OAS via promoting nuclear translocation of Nrf2 and inhibiting ferroptosis of testis.
Collapse
Affiliation(s)
- Jiayu Cai
- Traditional Chinese Medicine Department, Jinling Hospital, Nanjing 210002,China
| | - Lingxiong Song
- Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China
| | - Zebo Hu
- Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China
| | - Xiaojiao Gao
- Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China
| | - Yuhan Wang
- School of Public Health and Management, Ningxia Medicine University, Ningxia, China
| | - Yang Chen
- Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China
| | - Ke Xi
- Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China
| | - Xin Lu
- Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China
| | - Yonghui Shi
- Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China
| |
Collapse
|
16
|
Chang J, Wang J, Li X, Zhong Y. Predicting prospective therapeutic targets of Bombyx batryticatus for managing diabetic kidney disease through network pharmacology analysis. Medicine (Baltimore) 2024; 103:e39598. [PMID: 39287308 PMCID: PMC11404872 DOI: 10.1097/md.0000000000039598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/19/2024] Open
Abstract
We conducted network pharmacology and molecular docking analyses, and executed in vitro experiments to assess the mechanisms and prospective targets associated with the bioactive components of Bombyx batryticatus in the treatment of diabetic kidney disease (DKD). The bioactive components and potential targets of B batryticatus were sourced from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Using 5 disease databases, we conducted a comprehensive screening of potential disease targets specifically associated with DKD. Common targets shared between the bioactive components and disease targets were identified through the use of the R package, and subsequently, a protein-protein interaction network was established using data from the STRING database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses pertaining to the identified common targets were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Molecular docking simulations involving the bioactive components and their corresponding targets were modeled through AutoDock Vina and Pymol. Finally, to corroborate and validate these findings, experimental assays at the cellular level were conducted. Six bioactive compounds and 142 associated targets were identified for B batryticatus. Among the 796 disease targets associated with DKD, 56 targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed the involvement of these shared targets in diverse biological processes and signaling pathways, notably the PI3K-Akt signaling pathway. Molecular docking analyses indicated a favorable binding interaction between quercetin, the principal bioactive compound in B batryticatus, and RAC-alpha serine/threonine-protein kinase. Subsequently, in vitro experiments substantiated the inhibitory effect of quercetin on the phosphorylation level of PI3K and Akt. The present study provides theoretical evidence for a comprehensive exploration of the mechanisms and molecular targets by which B batryticatus imparts protective effects against DKD.
Collapse
Affiliation(s)
- Jingsheng Chang
- Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jue Wang
- Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xueling Li
- Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yifei Zhong
- Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| |
Collapse
|
17
|
Šakić Z, Atić A, Potočki S, Bašić-Jukić N. Sphingolipids and Chronic Kidney Disease. J Clin Med 2024; 13:5050. [PMID: 39274263 PMCID: PMC11396415 DOI: 10.3390/jcm13175050] [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: 07/30/2024] [Revised: 08/22/2024] [Accepted: 08/23/2024] [Indexed: 09/16/2024] Open
Abstract
Sphingolipids (SLs) are bioactive signaling molecules essential for various cellular processes, including cell survival, proliferation, migration, and apoptosis. Key SLs such as ceramides, sphingosine, and their phosphorylated forms play critical roles in cellular integrity. Dysregulation of SL levels is implicated in numerous diseases, notably chronic kidney disease (CKD). This review focuses on the role of SLs in CKD, highlighting their potential as biomarkers for early detection and prognosis. SLs maintain renal function by modulating the glomerular filtration barrier, primarily through the activity of podocytes. An imbalance in SLs can lead to podocyte damage, contributing to CKD progression. SL metabolism involves complex enzyme-catalyzed pathways, with ceramide serving as a central molecule in de novo and salvage pathways. Ceramides induce apoptosis and are implicated in oxidative stress and inflammation, while sphingosine-1-phosphate (S1P) promotes cell survival and vascular health. Studies have shown that SL metabolism disorders are linked to CKD progression, diabetic kidney disease, and glomerular diseases. Targeting SL pathways could offer novel therapeutic approaches for CKD. This review synthesizes recent research on SL signaling regulation in kidney diseases, emphasizing the importance of maintaining SL balance for renal health and the potential therapeutic benefits of modulating SL pathways.
Collapse
Affiliation(s)
- Zrinka Šakić
- Vuk Vrhovac University Clinic, Dugi dol 4a, 10000 Zagreb, Croatia
| | - Armin Atić
- Division of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Slavica Potočki
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Nikolina Bašić-Jukić
- Division of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| |
Collapse
|
18
|
Tio MC, Butler J, Zhu X, Obi Y, Yen TE, Kalantar-Zadeh K, Streja E, Dossabhoy NR, Hall ME, Shafi T. Individualized Risk of CKD Progression among US Adults. J Am Soc Nephrol 2024; 35:1076-1083. [PMID: 38749547 PMCID: PMC11377802 DOI: 10.1681/asn.0000000000000377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 05/06/2024] [Indexed: 06/20/2024] Open
Abstract
Key Points
A total of 8.42 million US adults have high CKD progression risk, and 4.77 million of them have eGFR >60 ml/min per 1.73 m2.An individual's absolute risk of CKD progression is important in the diagnosis and prognostication of CKD.
Background
CKD is currently defined using GFR or albuminuria. This is on the basis of the relative risk of mortality and kidney outcomes compared with a healthy population and does not consider an individual's absolute risk of CKD progression.
Methods
Using National Health and Nutrition Examination Survey data from 1999 to 2020, we characterized the individual-level absolute 3-year risk of ≥40% decline in eGFR (ml/min per 1.73 m2) or kidney failure (3-year risk) among US adults. We categorized the 3-year risk and considered ≥5% as high risk.
Results
Among 199.81 million US adults, 8.42 million (4%) had a 3-year risk ≥5%, including 1.04 million adults without CKD (eGFR ≥60 and albuminuria <30 mg/g). These high-risk adults without CKD as currently defined had risk factors including hypertension (98%), heart failure (72%), and diabetes (44%). A total of 15.51 million adults had CKD with preserved eGFR (eGFR ≥60 and albuminuria ≥30 mg/g)—3.73 million had a 3-year risk ≥5%, 41% of whom did not have diabetes and thus would not be screened for albuminuria using current screening recommendations. The 3-year risk of CKD progression was low (risk <5%) in 94% of the 5.66 million US adults with CKD stage G3a-A1 (eGFR 45 to <60 and albuminuria <30 mg/g).
Conclusions
Assessment of the individual's absolute risk of CKD progression allowed further risk stratification of patients with CKD and identified individuals without CKD, as currently defined, who were at high risk of CKD progression.
Podcast
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_06_18_ASN0000000000000377.mp3
Collapse
Affiliation(s)
- Maria Clarissa Tio
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Javed Butler
- Baylor Scott and White Research Institute, Dallas, Texas
- Division of Cardiology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Xiaoqian Zhu
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
- Department of Data Science, University of Mississippi Medical Center, Jackson, Mississippi
| | - Yoshitsugu Obi
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Timothy E Yen
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | | | - Elani Streja
- University of California Irvine School of Medicine, Irvine, California
| | - Neville R Dossabhoy
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
- Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Michael E Hall
- Division of Cardiology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
- Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Tariq Shafi
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
- Division of Kidney Diseases, Hypertension, and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, Texas
| |
Collapse
|
19
|
Uhlmann K, Reber E, Schonenberger KA, Stanga Z, Kurmann S. Should handgrip strength be considered when choosing the administration mode of oral nutritional supplements in geriatric patients? A secondary analysis of the MEDPass Trial. Nutrition 2024; 124:112429. [PMID: 38631270 DOI: 10.1016/j.nut.2024.112429] [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: 08/14/2023] [Revised: 11/09/2023] [Accepted: 03/17/2024] [Indexed: 04/19/2024]
Abstract
OBJECTIVE It is important to individualize nutrition therapy and to identify whether certain patient groups benefit from a specific intervention such as oral nutritional supplements (ONS). This study investigated whether patients with weak handgrip strength (HGS) benefit better from ONS administration in the Medication Pass Nutritional Supplement Program (MEDPass) mode regarding the individual coverage of energy and protein requirements throughout their hospitalization. METHODS A secondary analysis of the intention-to-treat data set of the randomized controlled MEDPass trial was conducted. Weak HGS was defined as <27 kg for men and <16 kg for women. Linear mixed-effect models adjusted for the stratification factors energy density of ONS and nutritional risk screening 2002 score were used to address the aim of the study. RESULTS We included 188 participants. Energy and protein coverage did not differ between the patients with weak or normal HGS depending on ONS administration mode (P = 0.084, P = 0.108). Patients with weak HGS and MEDPass administration mode tended to have the lowest energy and protein coverage (estimated mean, 77.2%; 95% confidence interval [CI], 69.3%-85% and estimated mean, 95.1%; 95% CI, 85.3%-105%, respectively). Patients with weak HGS and conventional ONS administration had the highest energy and protein coverage (estimated mean, 90%; 95% CI, 82.8%-97.2% and estimated mean, 110.2%; 95% CI, 101.3%-119%, respectively). CONCLUSION No clear recommendations regarding the mode of ONS administration depending on HGS can be made. In clinical practice, appetite and satiety in patients with weak HGS should be monitored, and the ONS administration mode should be adjusted accordingly.
Collapse
Affiliation(s)
- Katja Uhlmann
- Health Division, Nutrition and Dietetics, Bern University of Applied Sciences, Bern, Switzerland.
| | - Emilie Reber
- Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Katja A Schonenberger
- Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland; Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
| | - Zeno Stanga
- Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Silvia Kurmann
- Health Division, Nutrition and Dietetics, Bern University of Applied Sciences, Bern, Switzerland
| |
Collapse
|
20
|
Vellanki P, Umpierrez GE. Response to Comment on Kaminski et al. Assessment of Glycemic Control by Continuous Glucose Monitoring, Hemoglobin A1c, Fructosamine, and Glycated Albumin in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes. Diabetes Care 2024;47:267-271. Diabetes Care 2024; 47:e63-e64. [PMID: 39052906 DOI: 10.2337/dci24-0031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 05/13/2024] [Indexed: 07/27/2024]
Affiliation(s)
- Priyathama Vellanki
- Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Guillermo E Umpierrez
- Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| |
Collapse
|
21
|
Zhang R, Wang Q, Li Y, Li Q, Zhou X, Chen X, Dong Z. A new perspective on proteinuria and drug therapy for diabetic kidney disease. Front Pharmacol 2024; 15:1349022. [PMID: 39144629 PMCID: PMC11322372 DOI: 10.3389/fphar.2024.1349022] [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] [Received: 12/04/2023] [Accepted: 07/17/2024] [Indexed: 08/16/2024] Open
Abstract
Diabetic kidney disease (DKD) is one of the leading causes of end-stage renal disease worldwide and significantly increases the risk of premature death due to cardiovascular diseases. Elevated urinary albumin levels are an important clinical feature of DKD. Effective control of albuminuria not only delays glomerular filtration rate decline but also markedly reduces cardiovascular disease risk and all-cause mortality. New drugs for treating DKD proteinuria, including sodium-glucose cotransporter two inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists, have shown significant efficacy. Auxiliary treatment with proprietary Chinese medicine has also yielded promising results; however, it also faces a broader scope for development. The mechanisms by which these drugs treat albuminuria in patients with DKD should be described more thoroughly. The positive effects of combination therapy with two or more drugs in reducing albuminuria and protecting the kidneys warrant further investigation. Therefore, this review explores the pathophysiological mechanism of albuminuria in patients with DKD, the value of clinical diagnosis and prognosis, new progress and mechanisms of treatment, and multidrug therapy in patients who have type 2 diabetic kidney disease, providing a new perspective on the clinical diagnosis and treatment of DKD.
Collapse
Affiliation(s)
- Ruimin Zhang
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, China
| | - Qian Wang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, China
| | - Yaqing Li
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, China
| | - Qihu Li
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, China
| | - Xuefeng Zhou
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, China
| | - Xiangmei Chen
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, China
| | - Zheyi Dong
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, China
| |
Collapse
|
22
|
Toapanta N, Sánchez-Gavilan E, Guirao C, Leon Román J, Ramos N, Vergara A, Azancot M, Agraz I, Bermejo S, Montiel E, Molina C, Ribó M, Soler MJ. Pilot monitoring study in patients with diabetic kidney disease using NORA application. Nefrologia 2024; 44:519-526. [PMID: 39013756 DOI: 10.1016/j.nefroe.2024.07.001] [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: 10/17/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 07/18/2024] Open
Abstract
INTRODUCTION Diabetic Kidney Disease (DKD) is the most common cause of end-stage chronic kidney disease (CKD), conditioning these patients to a worse renal prognosis and higher cardiovascular mortality and/or requirement for renal replacement therapy. The use of novel information and communication technologies (ICTs) focused on the field of health, may facilitates a better quality of life and disease control in these patients. Our objective is to evaluate the effect of monitoring DKD patients using NORA-app. MATERIAL AND METHODS Prospective feasibility/validation study of NORA-app in patients with DKD stage G3bA3 or higher, followed in outpatient clinics of a tertiary care hospital. NORA-app is an application for smartphones designed to control risk factors, share educational medical information, communicate via chat with health professionals, increase treatment compliance (Morisky-Green), and collect patient reported outcomes such as anxiety and depression using HADs scale. Clinical-laboratory variables were collected at 3 months and compared to control patients who declined using NORA-app. RESULTS From 01/01/2021 to 03/03/2022 the use of NORA-app was offered to 118 patients, 82 accepted and 36 declined (controls). After a mean follow-up period of 6,04 months and at the time of data extraction 71 (86.6%) NORA-app patients remain active users, 2 have completed the follow-up at one year and 9 are inactive (3 due to death and 6 due to non-locatable). There were no differences in baseline characteristics including Creatinine [2.1 (1.6-2.4) vs. 1.9 (1.5-2.5)] mg/dL and alb/creat [962 (475-1784) vs. 1036 (560-2183)] mg/gr between Nora and control patients respectively. The therapeutic compliance rate in the NORA-app group was 77%, improving at 90 days to 91%. Patients in the NORA-group showed significantly lower levels of alb/creat than controls (768(411-1971) mg/g Vs 2039 (974-3214) p = 0.047) at 90-day follow-up. CONCLUSIONS In patients with DKD the use of NORA-app was maintained in the long-term, leading to high levels of treatment compliance, and achieving a better disease control. Our study suggests that the generalized use of ICTs may help in the personalized monitoring of these patients to delay the progression of kidney disease.
Collapse
Affiliation(s)
- Néstor Toapanta
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | | | - Cristina Guirao
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Juan Leon Román
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Natalia Ramos
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Ander Vergara
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - María Azancot
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Irene Agraz
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Sheila Bermejo
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Estefanía Montiel
- Serivicio de Neurología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Carlos Molina
- Serivicio de Neurología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Marc Ribó
- Serivicio de Neurología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - María José Soler
- Serivicio de Nefrología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| |
Collapse
|
23
|
Qiao Q, Liang K, Wang C, Wang L, Yan F, Chen L, Hou X. J-shaped association of the triglyceride glucose-body mass index with new-onset diabetes. Sci Rep 2024; 14:13882. [PMID: 38880800 PMCID: PMC11180648 DOI: 10.1038/s41598-024-64784-0] [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: 01/01/2024] [Accepted: 06/13/2024] [Indexed: 06/18/2024] Open
Abstract
The triglyceride glucose-body mass index (TyG-BMI) is a convenient and clinically significant indicator of insulin resistance. This study aims to investigate the correlation between TyG-BMI and the onset of new-onset diabetes and determine an optimal reflection point for TyG-BMI. An analysis was conducted on 1917 participants from the risk evaluation of cancers in Chinese diabetic individuals: a lONgitudinal (REACTION) study. Participants were categorized based on their TyG-BMI, and the relationship between TyG-BMI and the incidence of new-onset diabetes was explored through logistic regression models, smoothed curve fitting with restricted cubic spline, and a two-piecewise logistic regression model. The mean age of the participants was 57.60 ± 8.89 years, with 66.5% being females. The mean TyG-BMI was 223.3 ± 32.8. Ultimately, 137 individuals (7.1%) progressed to diabetes after three years. After adjusting for covariates, TyG-BMI exhibited a positive correlation with new-onset diabetes (odd ratios (OR) for each standard deviation increase = 1.330, 95% CI 1.110-1.595). The relationship between TyG-BMI and new-onset diabetes was non-linear, with a inflcetion point at 202.9. This study reveals a positive non-linear relationship between TyG-BMI and the risk of new-onset diabetes in Chinese middle-aged and elderly individuals. When TyG-BMI exceeds 202.9, there is a significantly heightened risk of new-onset diabetes. These findings offer valuable insights for preventing new-onset diabetes.
Collapse
Affiliation(s)
- Qincheng Qiao
- Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China
- The First Clinical Medical College, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Kai Liang
- Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People's Republic of China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, People's Republic of China
- Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People's Republic of China
| | - Chuan Wang
- Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People's Republic of China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, People's Republic of China
- Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People's Republic of China
| | - Lingshu Wang
- Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People's Republic of China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, People's Republic of China
- Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People's Republic of China
| | - Fei Yan
- Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People's Republic of China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, People's Republic of China
- Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People's Republic of China
| | - Li Chen
- Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China.
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People's Republic of China.
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, People's Republic of China.
- Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People's Republic of China.
| | - Xinguo Hou
- Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China.
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People's Republic of China.
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, People's Republic of China.
- Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People's Republic of China.
| |
Collapse
|
24
|
Arici M, Altun B, Araz M, Atmaca A, Demir T, Ecder T, Guz G, Gogas Yavuz D, Yildiz A, Yilmaz T. The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials. Front Med (Lausanne) 2024; 11:1384454. [PMID: 38947237 PMCID: PMC11214281 DOI: 10.3389/fmed.2024.1384454] [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] [Received: 02/09/2024] [Accepted: 05/22/2024] [Indexed: 07/02/2024] Open
Abstract
This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.
Collapse
Affiliation(s)
- Mustafa Arici
- Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Türkiye
| | - Bulent Altun
- Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Türkiye
| | - Mustafa Araz
- Department of Endocrinology and Metabolic Diseases, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye
| | - Aysegul Atmaca
- Department of Endocrinology and Metabolic Diseases, Ondokuz Mayis University Faculty of Medicine, Samsun, Türkiye
| | - Tevfik Demir
- Department of Endocrinology and Metabolic Diseases, Dokuz Eylul University Faculty of Medicine, Izmir, Türkiye
| | - Tevfik Ecder
- Department of Nephrology, Istinye University Faculty of Medicine, Istanbul, Türkiye
| | - Galip Guz
- Department of Nephrology, Gazi University Faculty of Medicine, Ankara, Türkiye
| | - Dilek Gogas Yavuz
- Section of Endocrinology and Metabolism, Marmara University School of Medicine, Istanbul, Türkiye
| | - Alaattin Yildiz
- Department of Nephrology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Türkiye
| | - Temel Yilmaz
- Clinics of Endocrinology and Metabolic Diseases, Florence Nightingale Hospital, Istanbul, Türkiye
| |
Collapse
|
25
|
Soputro NA, Ferguson EL, Ramos-Carpinteyro R, Chavali JS, Geskin A, Fareed K, Berglund R, Fergany AF, Stein RJ, Haber GP, Campbell SC, Weight CJ, Kaouk JH. Long-Term Functional and Oncologic Outcomes Following Robotic Partial and Radical Nephrectomy: A Report from a Single Institution with up to 15 Years of Follow-Up. J Endourol 2024; 38:573-583. [PMID: 38568897 DOI: 10.1089/end.2023.0543] [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: 04/05/2024] Open
Abstract
Objective: To evaluate the long-term functional and oncologic outcomes after robotic partial nephrectomy (RAPN) and radical nephrectomy (RARN). Materials and Methods: A retrospective review was performed on 1816 patients who underwent RAPN and RARN at our institution between January 2006 and January 2018. Patients with long-term follow-ups of at least 5 years were selected. Exclusion criteria included patients with a previous history of partial or radical nephrectomy, known genetic mutations, and whose procedures were performed for benign indications. Statistical analysis was performed with results as presented. Results: A total of 769 and 142 patients who underwent RAPN and RARN, respectively, met our inclusion criteria. The duration of follow-up was similar after the two procedures with a median of ∼100 months. The 5- and 10-year chronic kidney disease (CKD) upstaging-free survivals were 74.5% and 65.9% after RAPN and 53% and 46.4% after RARN, respectively. Older age was identified as a potential predictor for CKD progression after RARN, whereas older age, higher body mass index, baseline renal function, and ischemia time were shown to predict CKD progression after RAPN. Renal cell carcinoma-related mortality rates for RAPN and RARN were equally 1.1%. No statistically significant differences were identified in the local recurrence, metastatic, and disease-specific survival between the two procedures. Conclusion: Compared with RARN, RAPN conferred a better CKD progression-free survival. Several factors were identified as potential predictors for clinically significant CKD progression both in the early and late postoperative phase. Long-term oncologic outcomes between the two procedures remained similarly favorable.
Collapse
Affiliation(s)
- Nicolas A Soputro
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Ethan L Ferguson
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Jaya S Chavali
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Albert Geskin
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Khaled Fareed
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Ryan Berglund
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Amr F Fergany
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Robert J Stein
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Georges P Haber
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Steven C Campbell
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Jihad H Kaouk
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
| |
Collapse
|
26
|
Otsuka E, Kitamura M, Funakoshi S, Mukae H, Nishino T. Improving glycemic control: transitioning from dulaglutide to tirzepatide in patients with type 2 diabetes undergoing hemodialysis. Front Pharmacol 2024; 15:1362242. [PMID: 38873429 PMCID: PMC11169618 DOI: 10.3389/fphar.2024.1362242] [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] [Received: 12/27/2023] [Accepted: 05/06/2024] [Indexed: 06/15/2024] Open
Abstract
Background: Tirzepatide-a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist-is used to treat type 2 diabetes. However, the efficacy and safety of tirzepatide in patients undergoing hemodialysis remain unclear. Methods: We conducted a single-center retrospective study of patients with type 2 diabetes undergoing hemodialysis who were transitioned from dulaglutide to tirzepatide. We continuously monitored glucose levels in patients undergoing hemodialysis before and after switching from dulaglutide to tirzepatide. Results: Fourteen patients (mean age: 61.9 ± 9.9 years, male: female = 11:3) were included in this study. After switching to tirzepatide, time in range increased to 50.8% from 42.7% (p = 0.02), time above range decreased to 37.8% from 48.4% (p = 0.02), and mean glucose levels decreased to 137.4 mg/dL from 156.6 mg/dL (p = 0.006). In contrast, there was no significant difference in time below range before and after tirzepatide administration (11.3% and 8.9%) (p = 0.75). Three patients experienced dyspepsia (21.4%), and one patient experienced nausea (7.1%); however, no critical adverse events were reported. Conclusion: Transitioning from dulaglutide to tirzepatide improved glycemic control without increasing hypoglycemia in patients undergoing hemodialysis for type 2 diabetes.
Collapse
Affiliation(s)
- Emiko Otsuka
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Nagasaki Renal Center, Nagasaki, Japan
| | - Mineaki Kitamura
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Nagasaki Renal Center, Nagasaki, Japan
| | | | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomoya Nishino
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| |
Collapse
|
27
|
Gong Y, Bai X, Zhang D, Yang X, Qin Z, Yang Y, Zhou Y, Meng J, Liu X. Effect of DPP-4i inhibitors on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Lipids Health Dis 2024; 23:157. [PMID: 38796440 PMCID: PMC11128128 DOI: 10.1186/s12944-024-02132-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: 02/12/2024] [Accepted: 05/06/2024] [Indexed: 05/28/2024] Open
Abstract
AIMS About 20-40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. METHODS A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively. RESULTS A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg's and Egger's tests. CONCLUSIONS Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. INTERNATIONAL PROSPECTIVE REGISTER FOR SYSTEMATIC REVIEW (PROSPERO) NUMBER: CRD.42020144642.
Collapse
Affiliation(s)
- Yong Gong
- Department of Nephrology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xueyan Bai
- Department of Hemotology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Donglei Zhang
- Department of Hemotology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Xingsheng Yang
- Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Zheng Qin
- Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yu Yang
- Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yilun Zhou
- Department of Nephrology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
| | - Jie Meng
- Department of Pathology, Beijing TongRen Hospital, Capital Medical University, Beijing, China.
| | - Xin Liu
- Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
| |
Collapse
|
28
|
Yang X, Cai S, Gong J, Zhang J, Lian M, Chen R, Zhou L, Bai P, Liu B, Zhuang M, Tan H, Xu J, Li M. Characterization of gut microbiota in patients with stage 3-4 chronic kidney disease: a retrospective cohort study. Int Urol Nephrol 2024; 56:1751-1762. [PMID: 38085410 DOI: 10.1007/s11255-023-03893-7] [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: 05/09/2023] [Accepted: 11/16/2023] [Indexed: 04/09/2024]
Abstract
PURPOSE Multiple factors, such as dietary patterns, pharmaceutical interventions, and exposure to harmful substances, possess the capacity to influence gut microbiota composition. Gut microbiota dysbiosis has emerged as a significant contributor to the progression of chronic kidney disease (CKD) and its associated complications. By comprehending the intricacies of the intestinal microbiota, this research endeavor holds the potential to offer novel perspectives on potential strategies for mitigating CKD progression. METHODS In this retrospective analysis, we assessed gut microbiota composition in CKD patients. Fecal samples were collected from a cohort of 44 patients with stage 3-4 CKD, alongside a control group consisting of 132 healthy volunteers. Subsequently, 16 s rDNA sequencing was conducted to examine the composition of the gut microbiota. RESULTS Our findings revealed significant alterations in the diversity of intestinal microbiota in fecal samples between patients with stage 3-4 CKD and healthy subjects. Among the 475 bacterial genera, 164 were shared, while 242 dominant genera were exclusive to healthy subjects and 69 to CKD stages 3-4 samples. Notably, healthy volunteers exhibited a prevalence of intestinal Firmicutes and Bacteroidetes, whereas stage 3-4 CKD patients displayed higher abundance of Proteobacteria and Actinobacteria. The presence of uncultured Coprobacillus sp. notably contributed to distinguishing between the two groups. ROC curve analysis identified distinct microbiota with superior diagnostic efficacy for discriminating stage 3-4 CKD patients from healthy individuals. Metabolic pathway analysis revealed differing dominant pathways between the two groups-the NADH dehydrogenase pathway in healthy individuals and the phosphate acetyltransferase pathway in stage 3-4 CKD patients. Moreover, the CKD cohort displayed a higher proportion of Gram-negative bacteria and facultative anaerobes. CONCLUSIONS In conclusion, our study underscores the profound influence of gut microbiota dysbiosis on CKD progression. The distinct microbial profiles observed in CKD patients highlight the potential efficacy of microbiota-based interventions in mitigating CKD advancement.
Collapse
Affiliation(s)
- Xiali Yang
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Shiying Cai
- Department of Nursing, Shenzhen Hospital of Southern Medical University, Shenzhen, 518101, People's Republic of China
- School of Nursing, Southern Medical University, Guangzhou, 510515, People's Republic of China
| | - Jinsheng Gong
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Jun Zhang
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Minling Lian
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Rufu Chen
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Linghui Zhou
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Peijin Bai
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Bo Liu
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Minting Zhuang
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Honghong Tan
- Department of VIP Clinic, Shanghai East Hospital, Tongji University School of Medicine, No.150 Jimo Road, Shanghai, 200120, People's Republic of China.
| | - Juan Xu
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, Fujian Province, People's Republic of China.
| | - Meizhen Li
- Department of Nutrition, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, Fujian Province, People's Republic of China.
| |
Collapse
|
29
|
Adem M, Mekonen W, Ausman A, Ahmed M, Yimer A. Prevalence of chronic kidney disease and its associated factors among diabetes mellitus patients in Dessie Referral Hospital, South Wollo, Ethiopia. Sci Rep 2024; 14:9229. [PMID: 38649429 PMCID: PMC11035645 DOI: 10.1038/s41598-024-59184-3] [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: 07/06/2023] [Accepted: 04/08/2024] [Indexed: 04/25/2024] Open
Abstract
Diabetes mellitus shares a large proportion of kidney failure. Despite many patients suffering from diabetes mellitus and its complications in Dessie City, no study was conducted in the study area that shows the prevalence and associated factors of chronic kidney disease among diabetes mellitus patients. Therefore, this study aims to assess the prevalence of chronic kidney disease and its associated factors among adult diabetes mellitus patients attending Dessie Referral Hospital, South Wollo, Northeast Ethiopia. An institutional-based cross-sectional study was conducted at Dessie Referral Hospital among 267 randomly selected adult diabetic patients. Data were collected using questionnaires administered by interviewers. The glomerular filtration rate was estimated from serum creatinine levels. Data were entered into Epi-data version 4.6 and analyzed using SPSS version 26 software. Multi-variable logistic regression was used to determine the strength of association for the associated factors of chronic kidney disease. Variables with a p value < 0.05 were used to ascertain statistically significant associations. A total of 267 diabetic patients participated in this study. About 104 (39%) of the respondents were female and from the total, 133 (48.1%) were hypertensive. The overall prevalence of chronic kidney disease in this study was 31.5% (95% CI 25.3-37.1%). Being older (p-value = 0.003) and having hypertension (p-value = 0.043) were significant factors for chronic kidney disease among diabetes mellitus patients. This study found a high prevalence (31.5%) of chronic kidney disease among diabetic patients. Older age, having hypertension, and elevated serum creatinine were statistically significant associated factors of chronic kidney disease among patients with diabetes mellitus. Thus, clinicians should be aware of the high prevalence of chronic kidney disease in Dessie City. Moreover, emphasis should be given for old age and hypertension as contributing factors to the high prevalence in diabetic patients.
Collapse
Affiliation(s)
- Mohammed Adem
- Department of Biomedical Science, School of Medicine, College of Health Sciences, Woldia University, P.O. Box 400, Woldia, Ethiopia.
| | - Wondyefraw Mekonen
- Department of Physiology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Ahmed Ausman
- Department of Midwifery, College of Health Sciences, Samara University, Samara, Ethiopia
| | - Mohammed Ahmed
- Department of Public Health, College of Health Sciences, Woldia University, Woldia, Ethiopia
| | - Ali Yimer
- Department of Public Health, College of Health Sciences, Woldia University, Woldia, Ethiopia
| |
Collapse
|
30
|
Padoan F, Guarnaroli M, Brugnara M, Piacentini G, Pietrobelli A, Pecoraro L. Role of Nutrients in Pediatric Non-Dialysis Chronic Kidney Disease: From Pathogenesis to Correct Supplementation. Biomedicines 2024; 12:911. [PMID: 38672265 PMCID: PMC11048674 DOI: 10.3390/biomedicines12040911] [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: 03/16/2024] [Revised: 04/05/2024] [Accepted: 04/15/2024] [Indexed: 04/28/2024] Open
Abstract
Nutrition management is fundamental for children with chronic kidney disease (CKD). Fluid balance and low-protein and low-sodium diets are the more stressed fields from a nutritional point of view. At the same time, the role of micronutrients is often underestimated. Starting from the causes that could lead to potential micronutrient deficiencies in these patients, this review considers all micronutrients that could be administered in CKD to improve the prognosis of this disease.
Collapse
Affiliation(s)
| | | | - Milena Brugnara
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37126 Verona, Italy (A.P.)
| | | | | | | |
Collapse
|
31
|
Li L, Xiang T, Guo J, Guo F, Wu Y, Feng H, Liu J, Tao S, Fu P, Ma L. Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1β-dependent macrophage activation and tubular cell senescence. Nat Commun 2024; 15:3200. [PMID: 38615014 PMCID: PMC11016098 DOI: 10.1038/s41467-024-47315-3] [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: 06/05/2023] [Accepted: 03/25/2024] [Indexed: 04/15/2024] Open
Abstract
Histone lysine crotonylation (Kcr), as a posttranslational modification, is widespread as acetylation (Kac); however, its roles are largely unknown in kidney fibrosis. In this study, we report that histone Kcr of tubular epithelial cells is abnormally elevated in fibrotic kidneys. By screening these crotonylated/acetylated factors, a crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) is found to remarkably increase histone 3 lysine 9 crotonylation (H3K9cr) level without influencing H3K9ac in kidneys and tubular epithelial cells. The integrated analysis of ChIP-seq and RNA-seq of fibrotic kidneys reveal that the hub proinflammatory cytokine IL-1β, which is regulated by H3K9cr, play crucial roles in fibrogenesis. Furthermore, genetic and pharmacologic inhibition of ACSS2 both suppress H3K9cr-mediated IL-1β expression, which thereby alleviate IL-1β-dependent macrophage activation and tubular cell senescence to delay renal fibrosis. Collectively, our findings uncover that H3K9cr exerts a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive drug target to slow fibrotic kidney disease progression.
Collapse
Affiliation(s)
- Lingzhi Li
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China
| | - Ting Xiang
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China
| | - Jingjing Guo
- Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu, China
| | - Fan Guo
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China
| | - Yiting Wu
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China
| | - Han Feng
- Tulane Research and Innovation for Arrhythmia Discoveries-TRIAD Center, Tulane University School of Medicine, New Orleans, LA, USA
| | - Jing Liu
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China
| | - Sibei Tao
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China
| | - Ping Fu
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China.
| | - Liang Ma
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China.
| |
Collapse
|
32
|
Li C, Fu J, Ye Y, Li J, He Y, Fang T. The impact of vitamin D on the etiopathogenesis and the progression of type 1 and type 2 diabetes in children and adults. Front Endocrinol (Lausanne) 2024; 15:1360525. [PMID: 38650715 PMCID: PMC11033370 DOI: 10.3389/fendo.2024.1360525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 03/25/2024] [Indexed: 04/25/2024] Open
Abstract
Diabetes is a common chronic metabolic disease with complex causes and pathogenesis. As an immunomodulator, vitamin D has recently become a research hotspot in the occurrence and development of diabetes and its complications. Many studies have shown that vitamin D can reduce the occurrence of diabetes and delay the progression of diabetes complications, and vitamin D can reduce oxidative stress, inhibit iron apoptosis, promote Ca2+ influx, promote insulin secretion, and reduce insulin resistance. Therefore, the prevention and correction of vitamin D deficiency is very necessary for diabetic patients, but further research is needed to confirm what serum levels of vitamin D3 are maintained in the body. This article provides a brief review of the relationship between vitamin D and diabetes, including its acute and chronic complications.
Collapse
Affiliation(s)
- Candong Li
- Department of Endocrine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Jiaowen Fu
- Department of Endocrine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Yipeng Ye
- Department of Endocrine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Junsen Li
- Department of Endocrine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Yangli He
- Department of Health Care Centre, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Tuanyu Fang
- Department of Endocrine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| |
Collapse
|
33
|
Kim K, Crook J, Lu CC, Nyman H, Abdelaziz A, LaFleur J. Epidemiology of Diabetic Kidney Disease among US Veterans. Diabetes Metab Syndr Obes 2024; 17:1585-1596. [PMID: 38616990 PMCID: PMC11011711 DOI: 10.2147/dmso.s450370] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 02/15/2024] [Indexed: 04/16/2024] Open
Abstract
Rationale With a large number of patients and high mortality, diabetic kidney disease (DKD) imposes a significant burden on US health care. Although diabetes is the leading cause of chronic kidney disease and complications, the epidemiology of DKD in the contemporary US veteran population is generally unknown. Objective We aimed to estimate the rate of DKD progression and to measure the general epidemiology of DKD in the United States veteran population. Study Design We performed a retrospective observational research using electronic health-care records and administrative databases. Setting The DKD patient cohort was abstracted from the Veterans Health Administration health-record data from January 2016 to March 2022. Participants We defined DKD patients using the laboratory test data based on Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines. Analytic Approach Summary statistics include the five-year cumulative incidence of progression to an advanced stage from the DKD stage at the cohort entry date and prevalence at a series of single time points. Results A total of 685,288 patients (male [96%], mean age 62 years, Caucasian [64%], non-Hispanic [87%]) met our eligibility criteria. The 5-year cumulative incidence of progression to an advanced DKD stage or all-cause death from DKD stages G1 A2/A3, G2 A2/A3, G3a, and G3b were 52.0%, 47.4%, 50.5%, and 60.9%, respectively. In sum, 594,082 patients were classified as moderate or high risk as per KDIGO guidelines in 2021, and stages G3a and G3b accounted for 51.2% and 25.3%, respectively, of cases. Conclusion More than half of DKD patients underwent a stage progression or death within 5 years. A substantial number of DKD patients at an earlier stage might be left undetermined. The study findings warrant a revision of DKD patient identification and management in US veterans.
Collapse
Affiliation(s)
- Kibum Kim
- Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, IL, USA
- Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA
- VA Salt Lake City Health Care System, Salt Lake City, UT, USA
| | - Jacob Crook
- VA Salt Lake City Health Care System, Salt Lake City, UT, USA
- Division of Epidemiology, University of Utah, Salt Lake City, UT, USA
| | - Chao-Chin Lu
- VA Salt Lake City Health Care System, Salt Lake City, UT, USA
| | - Heather Nyman
- Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA
| | - Abdullah Abdelaziz
- Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, IL, USA
| | - Joanne LaFleur
- Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA
- VA Salt Lake City Health Care System, Salt Lake City, UT, USA
| |
Collapse
|
34
|
Hamzaei Z, Houlind MB, Kjeldsen LJ, Christensen LWS, Walls AB, Aharaz A, Olesen C, Coric F, Revell JHP, Ravn-Nielsen LV, Andersen TRH, Hedegaard U. Inappropriate prescribing in patients with kidney disease: A rapid review of prevalence, associated clinical outcomes and impact of interventions. Basic Clin Pharmacol Toxicol 2024; 134:439-459. [PMID: 38348501 DOI: 10.1111/bcpt.13986] [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: 10/07/2023] [Revised: 01/11/2024] [Accepted: 01/17/2024] [Indexed: 03/16/2024]
Abstract
BACKGROUND The prevalence of patients with chronic kidney disease (CKD) and polypharmacy is increasing and has amplified the importance of examining inappropriate prescribing (IP) in CKD. This review focuses on the latest research regarding the prevalence of IP in CKD and the related adverse clinical effects and explores new interventions against IP. METHOD A literature search was performed using PubMed, EMBASE and the Cochrane Library searching articles published between June 2016 and March 2022. RESULTS Twenty-seven studies were included. An IP prevalence of 12.6% to 96% and 0.3% to 66% was reported in hospital and outpatient settings, respectively. In nonhospital settings, the prevalence of IP varied between 3.9% and 60%. IP was associated with higher risk of hospitalisation (HR 1.46, 95% CI 1.17-1.81), higher bleeding rate (HR 2.34, 95% CI 1.32 to 3.37) and higher risk of all-cause mortality (OR 1.07, 95% CI 1.02 to 1.13). Three studies reported the impact of interventions on IP. CONCLUSION This review highlights widespread IP in CKD patients across healthcare settings, with varying prevalence rates. IP is substantially linked to adverse outcomes in patients. While limited interventions show promise, urgent research is needed to develop effective strategies addressing IP and improving CKD patient care.
Collapse
Affiliation(s)
- Zohra Hamzaei
- Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark
| | - Morten Baltzer Houlind
- The Capital Region Pharmacy, Herlev, Denmark
- Department of Clinical Research, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Louise Westberg Strejby Christensen
- The Capital Region Pharmacy, Herlev, Denmark
- Department of Clinical Research, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
| | - Anne Byriel Walls
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- The Capital Region Hospital Pharmacy, Copenhagen, Denmark
| | - Anissa Aharaz
- Department of Clinical Research, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
| | | | - Faruk Coric
- Hospital Pharmacy Funen, Odense University Hospital, Odense, Denmark
| | | | | | | | - Ulla Hedegaard
- Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark
| |
Collapse
|
35
|
Habiba UE, Khan N, Greene DL, Shamim S, Umer A. The therapeutic effect of mesenchymal stem cells in diabetic kidney disease. J Mol Med (Berl) 2024; 102:537-570. [PMID: 38418620 PMCID: PMC10963471 DOI: 10.1007/s00109-024-02432-w] [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: 05/02/2023] [Revised: 02/02/2024] [Accepted: 02/12/2024] [Indexed: 03/02/2024]
Abstract
Diabetes mellitus (DM) often causes chronic kidney damage despite best medical practices. Diabetic kidney disease (DKD) arises from a complex interaction of factors within the kidney and the whole body. Targeting specific disease-causing agents using drugs has not been effective in treating DKD. However, stem cell therapies offer a promising alternative by addressing multiple disease pathways and promoting kidney regeneration. Mesenchymal stem cells (MSCs) offer great promise due to their superior accessibility ratio from adult tissues and remarkable modes of action, such as the production of paracrine anti-inflammatory and cytoprotective substances. This review critically evaluates the development of MSC treatment for DKD as it moves closer to clinical application. Results from animal models suggest that systemic MSC infusion may positively impact DKD progression. However, few registered and completed clinical trials exist, and whether the treatments are effective in humans is still being determined. Significant knowledge gaps and research opportunities exist, including establishing the ideal source, dose, and timing of MSC delivery, better understanding of in vivo mechanisms, and developing quantitative indicators to obtain a more significant therapeutic response. This paper reviews recent literature on using MSCs in preclinical and clinical trials in DKD. Potent biomarkers related to DKD are also highlighted, which may help better understand MSCs' action in this disease progression. KEY MESSAGES: Mesenchymal stem cells have anti-inflammatory and paracrine effects in diabetic kidney disease. Mesenchymal stem cells alleviate in animal models having diabetic kidney disease. Mesenchymal stem cells possess promise for the treatment of diabetic kidney disease.
Collapse
Affiliation(s)
- Umm E Habiba
- Pak-American Hospital Pvt. Ltd, Jahangir Multiplex, Peshawar Road, Sector H-13, Islamabad, 44000, Pakistan.
- R3 Medical Research LLC, 10045 East Dynamite Boulevard Suite 260, Scottsdale, AZ, 85262, USA.
| | - Nasar Khan
- Pak-American Hospital Pvt. Ltd, Jahangir Multiplex, Peshawar Road, Sector H-13, Islamabad, 44000, Pakistan.
- R3 Medical Research LLC, 10045 East Dynamite Boulevard Suite 260, Scottsdale, AZ, 85262, USA.
- Bello Bio Labs and Therapeutics (SMC) Pvt. Ltd., Jahangir Multiplex, Peshawar Road, Sector H-13, Islamabad, 44000, Pakistan.
| | - David Lawrence Greene
- Pak-American Hospital Pvt. Ltd, Jahangir Multiplex, Peshawar Road, Sector H-13, Islamabad, 44000, Pakistan
- R3 Medical Research LLC, 10045 East Dynamite Boulevard Suite 260, Scottsdale, AZ, 85262, USA
- Bello Bio Labs and Therapeutics (SMC) Pvt. Ltd., Jahangir Multiplex, Peshawar Road, Sector H-13, Islamabad, 44000, Pakistan
| | - Sabiha Shamim
- Pak-American Hospital Pvt. Ltd, Jahangir Multiplex, Peshawar Road, Sector H-13, Islamabad, 44000, Pakistan
- R3 Medical Research LLC, 10045 East Dynamite Boulevard Suite 260, Scottsdale, AZ, 85262, USA
| | - Amna Umer
- Pak-American Hospital Pvt. Ltd, Jahangir Multiplex, Peshawar Road, Sector H-13, Islamabad, 44000, Pakistan
- R3 Medical Research LLC, 10045 East Dynamite Boulevard Suite 260, Scottsdale, AZ, 85262, USA
| |
Collapse
|
36
|
Chagnac A, Friedman AN. Measuring Albuminuria in Individuals With Obesity: Pitfalls of the Urinary Albumin-Creatinine Ratio. Kidney Med 2024; 6:100804. [PMID: 38576526 PMCID: PMC10993191 DOI: 10.1016/j.xkme.2024.100804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024] Open
Abstract
An increased urinary albumin excretion rate is an important early risk factor for chronic kidney disease and other major outcomes and is usually measured using the urinary albumin-creatinine ratio (ACR). Obesity is highly prevalent in the general and chronic kidney disease populations and is an independent risk factor for moderately increased albuminuria (henceforth, moderate albuminuria). In this review, we describe how the ACR was developed and used to define moderate albuminuria. We then investigate how biases related to urinary creatinine excretion are introduced into the ACR measurement and how the use of the 30-mg/g threshold decreases the performance of the test in populations with higher muscle mass, with a primary focus on why and how this occurs in the obese population. The discussion then raises several strategies that can be used to mitigate such bias. This review provides a comprehensive overview of the medical literature on the uses and limitations of ACR in individuals with obesity and critically assesses related issues. It also raises into question the widely accepted 30-mg/g threshold as universally adequate for the diagnosis of moderate albuminuria. The implications of our review are relevant for clinicians, epidemiologists, and clinical trialists.
Collapse
Affiliation(s)
- Avry Chagnac
- Maccabi Healthcare Services, Ramat Hasharon Medical Center, Israel
| | - Allon N. Friedman
- Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN
| |
Collapse
|
37
|
Wang Y, He X, Xue M, Yu H, He Q, Jin J. Integrated 16S rRNA sequencing and metabolomic analysis reveals the potential protective mechanism of Germacrone on diabetic nephropathy in mice. Acta Biochim Biophys Sin (Shanghai) 2024; 56:414-426. [PMID: 38429975 PMCID: PMC10984863 DOI: 10.3724/abbs.2024021] [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: 08/03/2023] [Accepted: 11/03/2023] [Indexed: 03/03/2024] Open
Abstract
Diabetic nephropathy (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Germacrone (Ger) possesses anti-inflammatory, antioxidant and anti-DN properties. However, it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota. This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics. Although there is no significant change in microbiota diversity, the structure of the gut microbiota in the DN group is quite different. Serratia_marcescens and Lactobacillus_iners are elevated in the model group but significantly decreased after Ger intervention ( P<0.05). Under the treatment of Ger, no significant differences in the diversity and richness of the gut microbiota are observed. An imbalance in the intestinal flora leads to the dysregulation of metabolites, and non-targeted metabolomics data indicate high expression of stearic acid in the DN group, and oleic acid could serve as a potential marker of the therapeutic role of Ger in the DN model. Overall, Ger improves kidney injury in diabetic mice, in part potentially by reducing the abundance of Serratia_marcescens and Lactobacillus_iners, as well as regulating the associated increase in metabolites such as oleic acid, lithocholic acid and the decrease in stearic acid. Our research expands the understanding of the relationship between the gut microbiota and metabolites in Ger-treated DN. This contributes to the usage of natural products as a therapeutic approach for the treatment of DN via microbiota regulation.
Collapse
Affiliation(s)
- Yunguang Wang
- Department of Nephrologythe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou310006China
| | - Xinxin He
- Department of Nephrologythe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou310006China
| | - Mengjiao Xue
- School of Clinical MedicineHangzhou Medical CollegeHangzhou311399China
| | - Huan Yu
- The Fourth Clinical Medical CollegeZhejiang Chinese Medical UniversityHangzhou310053China
| | - Qiang He
- Department of Nephrologythe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou310006China
| | - Juan Jin
- Department of Nephrologythe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou310006China
| |
Collapse
|
38
|
Sperl-Hillen J, Crain AL, Wetmore JB, Chumba LN, O’Connor PJ. A CKD Clinical Decision Support System: A Cluster Randomized Clinical Trial in Primary Care Clinics. Kidney Med 2024; 6:100777. [PMID: 38435072 PMCID: PMC10906435 DOI: 10.1016/j.xkme.2023.100777] [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] [Indexed: 03/05/2024] Open
Abstract
Rationale & Objective The study aimed to develop, implement, and evaluate a clinical decision support (CDS) system for chronic kidney disease (CKD) in a primary care setting, with the goal of improving CKD care in adults. Study Design This was a cluster randomized trial. Setting & Participants A total of 32 Midwestern primary care clinics were randomly assigned to either receive usual care or CKD-CDS intervention. Between April 2019 and March 2020, we enrolled 6,420 patients aged 18-75 years with laboratory-defined glomerular filtration rate categories of CKD Stage G3 and G4, and 1 or more of 6 CKD care gaps: absence of a CKD diagnosis, suboptimal blood pressure or glycated hemoglobin levels, indication for angiotensin-converting enzyme inhibitor or angiotensin receptor blocker but not prescribed, a nonsteroidal anti-inflammatory agent on the active medication list, or indication for a nephrology referral. Intervention The CKD-CDS provided personalized suggestions for CKD care improvement opportunities directed to both patients and clinicians at primary care encounters. Outcomes We assessed the proportion of patients meeting each of 6 CKD-CDS quality metrics representing care gap resolution after 18 months. Results The adjusted proportions of patients meeting quality metrics in CKD-CDS versus usual care were as follows: CKD diagnosis documented (26.6% vs 21.8%; risk ratio [RR], 1.17; 95% CI, 0.91-1.51); angiotensin-converting enzyme inhibitor or angiotensin receptor blocker prescribed (15.9% vs 16.1%; RR, 0.95; 95% CI, 0.76-1.18); blood pressure control (20.4% vs 20.2%; RR, 0.98; 95% CI, 0.84-1.15); glycated hemoglobin level control (21.4% vs 22.1%; RR, 1.00; 95% CI, 0.80-1.24); nonsteroidal anti-inflammatory agent not on the active medication list (51.5% vs 50.4%; RR, 1.03; 95% CI, 0.90-1.17); and referral or visit to a nephrologist (38.7% vs 36.1%; RR, 1.02; 95% CI, 0.79-1.32). Limitations We encountered an overall reduction in expected primary care encounters and obstacles to point-of-care CKD-CDS utilization because of the coronavirus disease 2019 pandemic. Conclusions The CKD-CDS intervention did not lead to a significant improvement in CKD quality metrics. The challenges to CDS use during the coronavirus disease 2019 pandemic likely influenced these results. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R18DK118463). Trial Registration clinicaltrials.gov Identifier: NCT03890588.
Collapse
Affiliation(s)
- JoAnn Sperl-Hillen
- HealthPartners Institute, Minneapolis, Minnesota
- Center for Chronic Care Innovation, HealthPartners Institute, Minneapolis, Minnesota
| | | | - James B. Wetmore
- Division of Nephrology, Hennepin Healthcare; Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, MN
| | - Lilian N. Chumba
- HealthPartners Institute, Minneapolis, Minnesota
- Center for Chronic Care Innovation, HealthPartners Institute, Minneapolis, Minnesota
| | - Patrick J. O’Connor
- HealthPartners Institute, Minneapolis, Minnesota
- Center for Chronic Care Innovation, HealthPartners Institute, Minneapolis, Minnesota
| |
Collapse
|
39
|
Wolff Gowdak LH, Galvão De Lima JJ, Adam EL, Kirnew Abud Manta IC, Reusing JO, David-Neto E, Machado César LA, Bortolotto LA. Coronary Artery Disease Assessment and Cardiovascular Events in Middle-Aged Patients on Hemodialysis. Mayo Clin Proc 2024; 99:411-423. [PMID: 38159095 DOI: 10.1016/j.mayocp.2023.05.007] [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: 05/03/2022] [Revised: 04/03/2023] [Accepted: 05/01/2023] [Indexed: 01/03/2024]
Abstract
OBJECTIVE To explore whether, in younger patients on dialysis with longer life expectancy, assessment of coronary artery disease (CAD) could identify individuals at higher risk of events and revascularization might improve outcomes in selected patients contrary to what had been observed in elderly patients. METHODS From August 1997 to January 2019, 2265 patients with stage 5 chronic kidney disease were prospectively referred for cardiovascular assessment. For this study, we selected 1374 asymptomatic patients aged between 18 and 64 years. After clinical risk stratification and cardiac scintigraphy by single-photon emission computed tomography, 866 patients underwent coronary angiography. The primary end point was the composite incidence of nonfatal/fatal major adverse cardiovascular events during a follow-up period of 0.1 to 189.7 months (median, 26 months). The secondary end point was all-cause mortality. RESULTS The primary end point occurred in 327 (23.8%) patients. Clinically stratified high-risk patients had a 3-fold increased risk of the primary end point. The prevalence of abnormal findings on perfusion scans was 29.2% (n=375), and significant CAD was found in 449 (51.8%) of 866 patients who underwent coronary angiography. An abnormal finding on myocardial perfusion scan and the presence of CAD were significantly associated with a 74% and 22% increased risk of cardiovascular events, respectively. In patients undergoing percutaneous coronary intervention or coronary artery bypass grafting (n=99), there was an 18% reduction in the risk of all-cause death relative to patients receiving medical treatment (P=.03). CONCLUSION In this cohort of middle-aged, asymptomatic patients on dialysis, assessment of CAD identified individuals at higher risk of events, and coronary intervention was associated with reducing the risk of death in selected patients.
Collapse
Affiliation(s)
- Luís Henrique Wolff Gowdak
- Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil.
| | - José Jayme Galvão De Lima
- Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Eduardo Leal Adam
- Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | | | - José Otto Reusing
- Renal Transplantation Unit, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Elias David-Neto
- Renal Transplantation Unit, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Luiz Antonio Machado César
- Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Luiz Aparecido Bortolotto
- Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| |
Collapse
|
40
|
Brockmeyer M, Parco C, Vargas KG, Westenfeld R, Jung C, Kelm M, Roden M, Akbulut C, Schlesinger S, Wolff G, Kuss O. Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data. J Nephrol 2024; 37:309-321. [PMID: 38236473 PMCID: PMC11043149 DOI: 10.1007/s40620-023-01858-8] [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: 06/09/2023] [Accepted: 11/29/2023] [Indexed: 01/19/2024]
Abstract
BACKGROUND Absolute treatment benefits-expressed as numbers needed to treat-of the glucose lowering and cardiovascular drugs, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors on renal outcomes remain uncertain. With the present meta-analysis of digitalized individual patient data, we aimed to display and compare numbers needed to treat of both drugs on a composite renal outcome. METHODS From Kaplan-Meier plots of major cardiovascular outcome trials of GLP-1 receptor agonists and SGLT2 inhibitors vs. placebo, we digitalized individual patient time-to-event information on composite renal outcomes with WebPlotDigitizer 4.2; numbers needed to treat from individual cardiovascular outcome trials were estimated using parametric Weibull regression models and compared to original data. Random-effects meta-analysis generated meta-numbers needed to treat with 95% confidence intervals (CI). RESULTS Twelve cardiovascular outcome trials (three for GLP-1 receptor agonists, nine for SGLT2 inhibitors) comprising 90,865 participants were included. Eight trials were conducted in primary type 2 diabetes populations, two in a primary heart failure and two in a primary chronic kidney disease population. Mean estimated glomerular filtration rate at baseline ranged between 37.3 and 85.3 ml/min/1.73 m2. Meta-analyses estimated meta-numbers needed to treat of 85 (95% CI 60; 145) for GLP-1 receptor agonists and 104 (95% CI 81; 147) for SGLT2 inhibitors for the composite renal outcome at the overall median follow-up time of 36 months. CONCLUSION The present meta-analysis of digitalized individual patient data revealed moderate and similar absolute treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors compared to placebo for a composite renal outcome.
Collapse
Affiliation(s)
- Maximilian Brockmeyer
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Claudio Parco
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Kris Gregory Vargas
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Ralf Westenfeld
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Christian Jung
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Malte Kelm
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Michael Roden
- Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
| | - Cihan Akbulut
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Sabrina Schlesinger
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Georg Wolff
- Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
- Division of Cardiology, Pulmonology and Vascular Medicine, Department of Conservative Medicine, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.
| | - Oliver Kuss
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Center for Health and Society, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| |
Collapse
|
41
|
Dimitriadis K, Damianaki A, Bletsa E, Pyrpyris N, Tsioufis P, Theofilis P, Beneki E, Tatakis F, Kasiakogias A, Oikonomou E, Petras D, Siasos G, Aggeli K, Tsioufis K. Renal Congestion in Heart Failure: Insights in Novel Diagnostic Modalities. Cardiol Rev 2024:00045415-990000000-00224. [PMID: 38427026 DOI: 10.1097/crd.0000000000000673] [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] [Indexed: 03/02/2024]
Abstract
Heart failure is increasingly prevalent and is estimated to increase its burden in the following years. A well-reported comorbidity of heart failure is renal dysfunction, where predominantly changes in the patient's volume status, tubular necrosis or other mechanical and neurohormonal mechanisms seem to drive this impairment. Currently, there are established biomarkers evaluating the patient's clinical status solely regarding the cardiovascular or renal system. However, as the coexistence of heart and renal failure is common and related to increased mortality and hospitalization for heart failure, it is of major importance to establish novel diagnostic techniques, which could identify patients with or at risk for cardiorenal syndrome and assist in selecting the appropriate management for these patients. Such techniques include biomarkers and imaging. In regards to biomarkers, several peptides and miRNAs indicative of renal or tubular dysfunction seem to properly identify patients with cardiorenal syndrome early on in the course of the disease, while changes in their serum levels can also be helpful in identifying response to diuretic treatment. Current and novel imaging techniques can also identify heart failure patients with early renal insufficiency and assess the volume status and the effect of treatment of each patient. Furthermore, by assessing the renal morphology, these techniques could also help identify those at risk of kidney impairment. This review aims to present all relevant clinical and trial data available in order to provide an up-to-date summary of the modalities available to properly assess cardiorenal syndrome.
Collapse
Affiliation(s)
- Kyriakos Dimitriadis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | | | - Evanthia Bletsa
- 3rd Department of Cardiology, Sotiria Hospital, University of Athens, Athens, Greece
| | - Nikolaos Pyrpyris
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Panagiotis Tsioufis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Panagiotis Theofilis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Eirini Beneki
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Fotis Tatakis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Alexandros Kasiakogias
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, Sotiria Hospital, University of Athens, Athens, Greece
| | | | - Gerasimos Siasos
- 3rd Department of Cardiology, Sotiria Hospital, University of Athens, Athens, Greece
| | - Konstantina Aggeli
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Konstantinos Tsioufis
- From the First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| |
Collapse
|
42
|
Habiba UE, Khan N, Greene DL, Shamim S, Umer A. The therapeutic effect of mesenchymal stem cells in diabetic kidney disease. J Mol Med (Berl) 2024. [DOI: https:/doi.org/10.1007/s00109-024-02432-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 02/02/2024] [Accepted: 02/12/2024] [Indexed: 03/07/2024]
Abstract
Abstract
Diabetes mellitus (DM) often causes chronic kidney damage despite best medical practices. Diabetic kidney disease (DKD) arises from a complex interaction of factors within the kidney and the whole body. Targeting specific disease-causing agents using drugs has not been effective in treating DKD. However, stem cell therapies offer a promising alternative by addressing multiple disease pathways and promoting kidney regeneration. Mesenchymal stem cells (MSCs) offer great promise due to their superior accessibility ratio from adult tissues and remarkable modes of action, such as the production of paracrine anti-inflammatory and cytoprotective substances. This review critically evaluates the development of MSC treatment for DKD as it moves closer to clinical application. Results from animal models suggest that systemic MSC infusion may positively impact DKD progression. However, few registered and completed clinical trials exist, and whether the treatments are effective in humans is still being determined. Significant knowledge gaps and research opportunities exist, including establishing the ideal source, dose, and timing of MSC delivery, better understanding of in vivo mechanisms, and developing quantitative indicators to obtain a more significant therapeutic response. This paper reviews recent literature on using MSCs in preclinical and clinical trials in DKD. Potent biomarkers related to DKD are also highlighted, which may help better understand MSCs’ action in this disease progression.
Key messages
Mesenchymal stem cells have anti-inflammatory and paracrine effects in diabetic kidney disease.
Mesenchymal stem cells alleviate in animal models having diabetic kidney disease.
Mesenchymal stem cells possess promise for the treatment of diabetic kidney disease.
Collapse
|
43
|
Hirsch JS, Danna SC, Desai N, Gluckman TJ, Jhamb M, Newlin K, Pellechio B, Elbedewe A, Norfolk E. Optimizing Care Delivery in Patients with Chronic Kidney Disease in the United States: Proceedings of a Multidisciplinary Roundtable Discussion and Literature Review. J Clin Med 2024; 13:1206. [PMID: 38592013 PMCID: PMC10932233 DOI: 10.3390/jcm13051206] [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: 12/15/2023] [Revised: 02/07/2024] [Accepted: 02/10/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Approximately 37 million individuals in the United States (US) have chronic kidney disease (CKD). Patients with CKD have a substantial morbidity and mortality, which contributes to a huge economic burden to the healthcare system. A limited number of clinical pathways or defined workflows exist for CKD care delivery in the US, primarily due to a lower prioritization of CKD care within health systems compared with other areas (e.g., cardiovascular disease [CVD], cancer screening). CKD is a public health crisis and by the year 2040, CKD will become the fifth leading cause of years of life lost. It is therefore critical to address these challenges to improve outcomes in patients with CKD. METHODS The CKD Leaders Network conducted a virtual, 3 h, multidisciplinary roundtable discussion with eight subject-matter experts to better understand key factors impacting CKD care delivery and barriers across the US. A premeeting survey identified topics for discussion covering the screening, diagnosis, risk stratification, and management of CKD across the care continuum. Findings from this roundtable are summarized and presented herein. RESULTS Universal challenges exist across health systems, including a lack of awareness amongst providers and patients, constrained care team bandwidth, inadequate financial incentives for early CKD identification, non-standardized diagnostic classification and triage processes, and non-centralized patient information. Proposed solutions include highlighting immediate and long-term financial implications linked with failure to identify and address at-risk individuals, identifying and managing early-stage CKD, enhancing efforts to support guideline-based education for providers and patients, and capitalizing on next-generation solutions. CONCLUSIONS Payers and other industry stakeholders have opportunities to contribute to optimal CKD care delivery. Beyond addressing the inadequacies that currently exist, actionable tactics can be implemented into clinical practice to improve clinical outcomes in patients at risk for or diagnosed with CKD in the US.
Collapse
Affiliation(s)
- Jamie S. Hirsch
- Northwell Health, Northwell Health Physician Partners, 100 Community Drive, Floor 2, Great Neck, NY 11021, USA
| | - Samuel Colby Danna
- VA Southeast Louisiana Healthcare System, 2400 Canal Street, New Orleans, LA 70119, USA
| | - Nihar Desai
- Section of Cardiovascular Medicine, Yale School of Medicine, 800 Howard Avenue, Ste 2nd Floor, New Haven, CT 06519, USA
| | - Ty J. Gluckman
- Providence Heart Institute, Center for Cardiovascular Analytics, Research, and Data Science (CARDS), 9205 SW Barnes Road, Suite 598, Portland, OR 97225, USA
| | - Manisha Jhamb
- Division of Renal-Electrolyte, University of Pittsburgh, 3550 Terrace St., Scaife A915, Pittsburgh, PA 15261, USA
| | - Kim Newlin
- Sutter Health, Sutter Roseville Medical Center, 1 Medical Plaza Drive, Roseville, CA 95661, USA
| | - Bob Pellechio
- RWJ Barnabas Health, Cooperman Barnabas Medical Center, 95 Old Short Hills Rd., West Orange, NJ 07052, USA
| | - Ahlam Elbedewe
- The Kinetix Group, 29 Broadway 26th Floor, New York, NY 10006, USA
| | - Evan Norfolk
- Geisinger Medical Center—Nephrology, 100 North Academy Avenue, Danville, PA 17822, USA
| |
Collapse
|
44
|
He M, Wei W, Zhang Y, Xiang Z, Peng D, Kasimumali A, Rong S. Gut microbial metabolites SCFAs and chronic kidney disease. J Transl Med 2024; 22:172. [PMID: 38369469 PMCID: PMC10874542 DOI: 10.1186/s12967-024-04974-6] [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: 11/18/2023] [Accepted: 02/11/2024] [Indexed: 02/20/2024] Open
Abstract
The global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD's development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies.
Collapse
Affiliation(s)
- Meng He
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Wenqian Wei
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Yichen Zhang
- Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Zhouxia Xiang
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Dan Peng
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Ayijiaken Kasimumali
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Shu Rong
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
| |
Collapse
|
45
|
Kaminski CY, Galindo RJ, Navarrete JE, Zabala Z, Moazzami B, Gerges A, McCoy RG, Fayfman M, Vellanki P, Idrees T, Peng L, Umpierrez GE. Assessment of Glycemic Control by Continuous Glucose Monitoring, Hemoglobin A1c, Fructosamine, and Glycated Albumin in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes. Diabetes Care 2024; 47:267-271. [PMID: 38085705 PMCID: PMC11148628 DOI: 10.2337/dc23-1276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 11/13/2023] [Indexed: 01/21/2024]
Abstract
OBJECTIVE Patients with diabetes and end-stage kidney disease (ESKD) may experience "burnt-out diabetes," defined as having an HbA1c value <6.5% without antidiabetic therapy for >6 months. We aim to assess glycemic control by continuous glucose monitoring (Dexcom G6 CGM) metrics and glycemic markers in ESKD patients on hemodialysis with burnt-out diabetes. RESEARCH DESIGN AND METHODS In this pilot prospective study, glycemic control was assessed by continuous glucose monitoring (CGM), HbA1c measures, and glycated albumin and fructosamine measurements in patients with burnt-out diabetes (n = 20) and without a history of diabetes (n = 20). RESULTS Patients with burnt-out diabetes had higher CGM-measured daily glucose levels, lower percent time in the range 70-180 mg/dL, higher percent time above range (>250 mg/dL), and longer duration of hyperglycemia >180 mg/dL (hours/day) compared with patients without diabetes (all P < 0.01). HbA1c and fructosamine levels were similar; however, patients with burnt-out diabetes had higher levels of glycated albumin than did patients without diabetes. CONCLUSIONS The use of CGM demonstrated that patients with burnt-out diabetes have significant undiagnosed hyperglycemia. CGM and glycated albumin provide better assessment of glycemic control than do values of HbA1c and fructosamine in patients with ESKD.
Collapse
Affiliation(s)
| | - Rodolfo J. Galindo
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Jose E. Navarrete
- Division of Nephrology, Department of Medicine, Emory University, Atlanta, GA
| | - Zohyra Zabala
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Bobak Moazzami
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Amany Gerges
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Rozalina G. McCoy
- Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
- University of Maryland Institute for Health Computing, Bethesda, MD
| | - Maya Fayfman
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Priyathama Vellanki
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Thaer Idrees
- Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA
| | - Limin Peng
- Emory University Rollins School of Public Health, Atlanta, GA
| | | |
Collapse
|
46
|
Lv D, Lin Z, Liao X, Peng R, Liu H, Wu T, Wu K, Sun Y, Zhang Z. Sfrp2 promotes renal dysfunction of diabetic kidney disease via modulating Fzd5-induced cytosolic calcium ion concentration and CaMKII/Mek/Erk pathway in mesangial cells. Biochim Biophys Acta Mol Basis Dis 2024; 1870:166933. [PMID: 37951508 DOI: 10.1016/j.bbadis.2023.166933] [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: 07/05/2023] [Revised: 10/24/2023] [Accepted: 10/26/2023] [Indexed: 11/14/2023]
Abstract
OBJECTIVE Mesangial cells (MCs) in the kidney play central role in maintaining glomerular integrity, and their abnormal proliferation leads to major glomerular diseases including diabetic kidney disease (DKD). Although high blood glucose elicits MCs impairment, the underlying molecular mechanism is poorly understood. The present study aimed to investigate the effect of secreted frizzled-related protein 2 (Sfrp2) from single-nucleus RNA profiling on MC proliferation of DKD in vitro and in vivo and explored the specific mechanisms. RESULTS By snRNA-seq analysis of isolated renal cells from leptin receptor-deficient db/db mice and control db/m mice, we found that Sfrp2 was increased in the MCs of DKD in comparison to other intrinsic renal cells, which was further verified in vitro and in vivo. We also found that the expression of Sfrp2 was significantly upregulated in DKD patients and correlated with renal function, demonstrating that Sfrp2 might serve as an independent biomarker for DKD patients. Functionally, we showed the loss and acquisition of Sfrp2 affected cytosolic Ca2+ concentration, cell proliferation and fibrosis of MC, albuminuria and kidney injury in vitro and in vivo. Mechanistically, we identify c-Jun as a transcription factor of Sfrp2 promoting its transcription, and the Ca2+ signaling related protein frizzled receptor 5 (Fzd5) as the binding protein of Sfrp2. And we further found Sfrp2 promoted Fzd5-induced cytosolic Ca2+ concentration and the downstream CaMKII/Mek/Erk pathway activation, leading to MC proliferation and fibrosis in DKD. CONCLUSION Our study revealed a novel involvement for Sfrp2 in the regulation of MC function and the effect of Sfrp2 on cell proliferation and fibrosis of MC via the Fzd5/Ca2+/CaMKII/Mek/Erk pathway, implying that Sfrp2 may be a possible biomarker and therapeutic target for DKD.
Collapse
Affiliation(s)
- Dan Lv
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Ziyue Lin
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Xiaohui Liao
- Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Rui Peng
- Department of Bioinformatics, Chongqing Medical University, Chongqing 400016, China
| | - Handeng Liu
- Laboratory of Tissue and Cell Biology, Experimental Teaching Center, Chongqing Medical University, Chongqing 400016, China
| | - Tianhui Wu
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Keqian Wu
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Yan Sun
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
| | - Zheng Zhang
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
| |
Collapse
|
47
|
Pollock C, Sanchez JJG, Carrero JJ, Kumar S, Pecoits-Filho R, Lam CSP, Chen H, Kanda E, Lainscak M, Wheeler DC. Glucose-lowering treatment pathways of individuals with chronic kidney disease and type 2 diabetes according to the Kidney Disease: Improving Global Outcomes 2012 risk classification. Diabet Med 2024; 41:e15200. [PMID: 37578188 DOI: 10.1111/dme.15200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 08/08/2023] [Accepted: 08/11/2023] [Indexed: 08/15/2023]
Abstract
AIMS To describe treatment pathways for key glucose-lowering therapies in individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D) using retrospective data from DISCOVER CKD (NCT04034992). METHODS Data were extracted from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics data (2008-2020) and the US integrated Limited Claims and Electronic Health Records Database (LCED; 2012-2019). Eligible individuals were aged ≥18 years with CKD, identified by two consecutive estimated glomerular filtration rate (eGFR) measures (15-<75 mL/min/1.73 m2 ; 90-730 days apart; index date was the second measurement) and T2D. Chronological treatment pathways for glucose-lowering therapies prescribed on or after CKD index to end of follow-up were computed. Median time and proportion of overall follow-up time on treatment were described for each therapy by database and by eGFR and urinary albumin-to-creatinine ratio (UACR) categories. RESULTS Of 36,951 and 4339 eligible individuals in the CPRD and LCED, respectively, median baseline eGFR was 67.8 and 64.9 mL/min/1.73 m2 ; 64.2 and 63.9% received metformin prior to index; and median (interquartile range) time on metformin during follow-up was 917 (390-1671) and 454 (192-850) days (accounting for ~75% of follow-up time in both databases). The frequency of combination treatment increased over time. There were trends towards decreased metformin prescriptions with decreasing eGFR and increasing UACR within each eGFR category. CONCLUSIONS Individuals with CKD and T2D had many combinations of therapies and substantial follow-up time on therapy. These results highlight opportunities for improved CKD management.
Collapse
Affiliation(s)
- Carol Pollock
- Royal North Shore Hospital, Kolling Institute, University of Sydney, St Leonards, New South Wales, Australia
| | | | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Supriya Kumar
- Real World Data Science, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, USA
| | - Roberto Pecoits-Filho
- School of Medicine, Pontifical Catholic University of Parana, Curitiba, Brazil
- Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA
| | - Carolyn S P Lam
- Department of Cardiology, National Heart Centre Singapore, Singapore City, Singapore
- Duke-NUS Medical School, Singapore City, Singapore
| | - Hungta Chen
- Medical and Payer Evidence Statistics, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, USA
| | | | - Mitja Lainscak
- Division of Cardiology, General Hospital Murska Sobota, and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - David C Wheeler
- Department of Renal Medicine, University College London, London, UK
| |
Collapse
|
48
|
Lopes-Virella MF, Hammad SM, Baker NL, Klein RL, Hunt KJ. Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes. Biomedicines 2024; 12:190. [PMID: 38255295 PMCID: PMC10813484 DOI: 10.3390/biomedicines12010190] [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: 11/22/2023] [Revised: 12/25/2023] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Abnormalities of sphingolipid metabolism play an important role in diabetes. We compared sphingolipid levels in plasma and in isolated lipoproteins between healthy control subjects and two groups of patients, one with chronic kidney disease without diabetes (ND-CKD), and the other with type 2 diabetes and macroalbuminuria (D-MA). Ceramides, sphingomyelins, and sphingoid bases and their phosphates in LDL were higher in ND-CKD and in D-MA patients compared to controls. However, ceramides and sphingoid bases in HDL2 and HDL3 were lower in ND-CKD and in D-MA patients than in controls. Sphingomyelins in HDL2 and HDL3 were lower in D-MA patients than in controls but were normal in ND-CKD patients. Compared to controls, lactosylceramides in LDL and VLDL were higher in ND-CKD patients but not in D-MA patients. However, lactosylceramides in HDL2 and HDL3 were lower in both ND-CKD and D-MA patients than in controls. Plasma hexosylceramides in ND-CKD patients were increased and sphingoid bases decreased in both ND-CKD and D-MA patients. However, hexosylceramides in LDL, HDL2, and HDL3 were higher in ND-CKD patients than in controls. In D-MA patients, only C16:0 hexosylceramide in LDL was higher than in controls. The data suggest that sphingolipid measurement in lipoproteins, rather than in whole plasma, is crucial to decipher the role of sphingolipids in kidney disease.
Collapse
Affiliation(s)
- Maria F. Lopes-Virella
- Department of Medicine, Division of Diabetes, Endocrinology and Medical Genetics, Medical University of South Carolina, Charleston, SC 29425, USA
- Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA;
| | - Samar M. Hammad
- Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Nathaniel L. Baker
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA;
| | - Richard L. Klein
- Department of Medicine, Division of Diabetes, Endocrinology and Medical Genetics, Medical University of South Carolina, Charleston, SC 29425, USA
- Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA;
| | - Kelly J. Hunt
- Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA;
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA;
| |
Collapse
|
49
|
ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Ekhlaspour L, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Stanton RC, Gabbay RA. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S219-S230. [PMID: 38078574 PMCID: PMC10725805 DOI: 10.2337/dc24-s011] [Citation(s) in RCA: 75] [Impact Index Per Article: 75.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Collapse
|
50
|
Meir J, Huang L, Mahmood S, Whiteson H, Cohen S, Aronow WS. The vascular complications of diabetes: a review of their management, pathogenesis, and prevention. Expert Rev Endocrinol Metab 2024; 19:11-20. [PMID: 37947481 DOI: 10.1080/17446651.2023.2279533] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 11/01/2023] [Indexed: 11/12/2023]
Abstract
INTRODUCTION This review highlights the pathogenesis of both microvascular and macrovascular complications of diabetes and how these mechanisms influence both the management and preventative strategies of these complications. The cumulative data shown in this review suggest hyperglycemic and blood pressure control remain central to this intricate process. AREAS COVERED We reviewed the literature including retrospective, prospective trials as well as meta-analysis, and post hoc analysis of randomized trials on microvascular andmacrovascular complications. EXPERT OPINION Further research is needed to explore the ideal intervention targets and preventative strategies needed to prevent macrovascular complications. Furthermore, as the data for trials looking at microvascular complications lengthen more long-term data will further elucidate the role that the duration of diabetes has on these complications. Additionally, trials looking to maximize hyperglycemic control with multiple agents in diabetes, such as metformin, SGL2isand GLP-1 receptor agonists are currently in process, which will have implications for rates of microvascular as well as macrovascular complications.
Collapse
Affiliation(s)
- Juliet Meir
- Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Lillian Huang
- Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Sumaita Mahmood
- Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Harris Whiteson
- Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Scott Cohen
- Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Wilbert S Aronow
- Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| |
Collapse
|