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Xu X, Ma R, Zhang X, Guo H, Keerman M, Wang X, Li Y, Maimaitijiang R, He J, Guo S. Association between renal function trajectories and risk of cardiovascular disease: a prospective cohort study. Ann Med 2024; 56:2427907. [PMID: 39618071 PMCID: PMC12002098 DOI: 10.1080/07853890.2024.2427907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 05/21/2024] [Accepted: 10/26/2024] [Indexed: 04/18/2025] Open
Abstract
INTRODUCTION It is unclear whether changing trajectories of renal function will increase the risk prediction information of cardiovascular disease (CVD). This study aimed to evaluate the trajectory patterns of estimated glomerular filtration rate (eGFR) and the association between eGFR trajectories and CVD risk. METHODS A total of 4742 participants were included in the cohort from the 51st Regiment of Xinjiang Production and Construction Corps. The study endpoint was the occurrence of CVD events. eGFR trajectories were identified using a linear mixed-effects model in four distinct patterns. Multivariate Cox proportional hazards models analysed the correlations between eGFR trajectories and CVD. RESULTS During a median follow-up period of 5.7 years, a total of 559 (11.8%) CVD, 404 (8.5%) myocardial infarction (MI), 244 (5.2%) ischemic stroke (IS), and 62 (1.3%) heart failure (HF) incidents occurred. After multivariable adjustment, gradual decline trajectory increased the risk of CVD (HR 1.42, 95% CI 1.16-1.74), MI (HR 1.41, 95% CI 1.11-1.79), and IS (HR 1.41, 95% CI 1.04-1.92); gradual increase trajectory reduced the risk of CVD (HR 0.40, 95% CI 0.25-0.64) and MI (HR 0.49, 95% CI 0.29-0.81). Consistent results were obtained in sensitivity and subgroup analyses. CONCLUSIONS Decline and increase of renal function were related to the risk of CVD, MI, and IS in the rural areas of Xinjiang. Monitoring eGFR changing trajectory is of great significance in improving the risk of CVD.
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Affiliation(s)
- Xuehong Xu
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Rulin Ma
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Xianghui Zhang
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Heng Guo
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Mulatibieke Keerman
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Xinping Wang
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Yu Li
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Remina Maimaitijiang
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Jia He
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
| | - Shuxia Guo
- Department of Public Health, Shihezi
University School of Medicine, Shihezi,
China
- Department of National Health Commission Key
Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The
First Affiliated Hospital of Shihezi University Medical College,
Shihezi, China
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Zhao Z, Wan Y, Fu H, Ying S, Zhang P, Meng H, Song Y, Fu N. Lipid-lowering drugs and risk of rapid renal function decline: a mendelian randomization study. BMC Med Genomics 2024; 17:248. [PMID: 39379957 PMCID: PMC11463126 DOI: 10.1186/s12920-024-02020-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 09/25/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) patients face the risk of rapid kidney function decline leading to adverse outcomes like dialysis and mortality. Lipid metabolism might contribute to acute kidney function decline in CKD patients. Here, we utilized the Mendelian Randomization approach to investigate potential causal relationships between drug target-mediated lipid phenotypes and rapid renal function decline. METHODS In this study, we utilized two methodologies: summarized data-based Mendelian randomization (SMR) and inverse variance-weighted Mendelian randomization (IVW-MR), to approximate exposure to lipid-lowering drugs. This entailed leveraging expression quantitative trait loci (eQTL) for drug target genes and genetic variants proximal to drug target gene regions, which encode proteins associated with low-density lipoprotein (LDL) cholesterol, as identified in genome-wide association studies. The objective was to investigate causal associations with the progression of rapid kidney function decline. RESULTS The SMR analysis revealed a potential association between high expression of PCSK9 and rapid kidney function decline (OR = 1.11, 95% CI= [1.001-1.23]; p = 0.044). Similarly, IVW-MR analysis demonstrated a negative association between LDL cholesterol mediated by HMGCR and kidney function decline (OR = 0.74, 95% CI = 0.60-0.90; p = 0.003). CONCLUSION Genetically predicted inhibition of HMGCR is linked with the progression of kidney function decline, while genetically predicted PCSK9 inhibition is negatively associated with kidney function decline. Future research should incorporate clinical trials to validate the relevance of PCSK9 in preventing kidney function decline.
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Affiliation(s)
- Zhicheng Zhao
- Graduate school of Tianjin Medical University, Tianjin, 300070, China
- Department of Cardiology, Tianjin Chest Hospital, Tianjin University, Tianjin, 300222, China
| | - Yu Wan
- Graduate school of Tianjin Medical University, Tianjin, 300070, China
| | - Han Fu
- Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shuo Ying
- Department of Cardiology, Tianjin Chest Hospital, Tianjin University, Tianjin, 300222, China
| | - Peng Zhang
- Department of Cardiology, Tianjin Chest Hospital, Tianjin University, Tianjin, 300222, China
| | - Haoyu Meng
- Graduate school of Tianjin Medical University, Tianjin, 300070, China
| | - Yu Song
- Graduate school of Tianjin Medical University, Tianjin, 300070, China
| | - Naikuan Fu
- Department of Cardiology, Tianjin Chest Hospital, Tianjin University, Tianjin, 300222, China.
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Sartore G, Ragazzi E, Deppieri E, Lapolla A. Is eGFR Slope a Novel Predictor of Chronic Complications of Type 2 Diabetes Mellitus? A Systematic Review and Meta-Analysis. J Diabetes Res 2024; 2024:8859678. [PMID: 38268787 PMCID: PMC10807937 DOI: 10.1155/2024/8859678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 12/20/2023] [Accepted: 01/10/2024] [Indexed: 01/26/2024] Open
Abstract
Background Diabetic kidney disease affects approximately 40% of patients with type 2 diabetes mellitus (T2DM) and is associated with an increased risk of end-stage kidney disease (ESKD) and cardiovascular (CV) events, as well as increased mortality. Among the indicators of decline in renal function, the eGFR slope is acquiring an increasing clinical interest. The aim of this study was to evaluate, through a systematic review of the literature and meta-analysis of the collected data, the association between the decline of the eGFR slope, chronic complications, and mortality of T2DM patients, in order to understand whether or not the eGFR slope can be defined as a predictive indicator of complications in T2DM. Methods The review and meta-analysis were conducted according to PRISMA guidelines considering published studies on patients with T2DM. A scientific literature search was carried out on PubMed from January 2003 to April 2023 with subsequent selection of scientific papers according to the inclusion criteria. Results Fifteen studies were selected for meta-analysis. Risk analysis as hazard ratio (HR) indicated a significant association between all events considered (all-cause mortality, CV events, ESKD, and microvascular events) for patients with steeper eGFR slope decline than subjects with stable eGFR. Calculated HRs (with 95% CI) were as follows: for all-cause mortality, 2.31 (1.70-3.15); for CV events, 1.73 (1.43-2.08); for ESKD, 1.54 (1.45-1.64); and for microvascular events, 2.07 (1.57-2.73). Overall HR was 1.82 (1.72-1.92). Conclusions An association between rapid eGFR decline and chronic diabetes complications was demonstrated, suggesting that eGFR slope variability significantly impacts the course of T2DM and that eGFR slope should be considered as a predictor for chronic complications in patients with T2DM. According to the obtained results, the therapeutic management of the patient with diabetes should not focus exclusively on glycaemic control, and particular attention should be paid to preserve renal function.
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Affiliation(s)
- Giovanni Sartore
- Department of Medicine-DIMED, University of Padua, Padova, Italy
| | | | - Elena Deppieri
- Department of Medicine-DIMED, University of Padua, Padova, Italy
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Nashawi M, Ahmed MS, Amin T, Abualfoul M, Chilton R. Cardiovascular benefits from SGLT2 inhibition in type 2 diabetes mellitus patients is not impaired with phosphate flux related to pharmacotherapy. World J Cardiol 2021; 13:676-694. [PMID: 35070111 PMCID: PMC8716977 DOI: 10.4330/wjc.v13.i12.676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 08/02/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
The beneficial cardiorenal outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) have been substantiated by multiple clinical trials, resulting in increased interest in the multifarious pathways by which their mechanisms act. The principal effect of SGLT2i (-flozin drugs) can be appreciated in their ability to block the SGLT2 protein within the kidneys, inhibiting glucose reabsorption, and causing an associated osmotic diuresis. This ameliorates plasma glucose elevations and the negative cardiorenal sequelae associated with the latter. These include aberrant mitochondrial metabolism and oxidative stress burden, endothelial cell dysfunction, pernicious neurohormonal activation, and the development of inimical hemodynamics. Positive outcomes within these domains have been validated with SGLT2i administration. However, by modulating the sodium-glucose cotransporter in the proximal tubule (PT), SGLT2i consequently promotes sodium-phosphate cotransporter activity with phosphate retention. Phosphatemia, even at physiologic levels, poses a risk in cardiovascular disease burden, more so in patients with type 2 diabetes mellitus (T2DM). There also exists an association between phosphatemia and renal impairment, the latter hampering cardiovascular function through an array of physiologic roles, such as fluid regulation, hormonal tone, and neuromodulation. Moreover, increased phosphate flux is associated with an associated increase in fibroblast growth factor 23 levels, also detrimental to homeostatic cardiometabolic function. A contemporary commentary concerning this notion unifying cardiovascular outcome trial data with the translational biology of phosphate is scant within the literature. Given the apparent beneficial outcomes associated with SGLT2i administration notwithstanding negative effects of phosphatemia, we discuss in this review the effects of phosphate on the cardiometabolic status in patients with T2DM and cardiorenal disease, as well as the mechanisms by which SGLT2i counteract or overcome them to achieve their net effects. Content drawn to develop this conversation begins with proceedings in the basic sciences and works towards clinical trial data.
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Affiliation(s)
- Mouhamed Nashawi
- Department of Internal Medicine, Baylor Scott and White All Saints Medical Center, Fort Worth, TX 76132, United States.
| | - Mahmoud S Ahmed
- Division of Medicine-Cardiology, UT Health San Antonio, San Antonio, TX 78229, United States
| | - Toka Amin
- Division of Medicine-Cardiology, UT Health San Antonio, San Antonio, TX 78229, United States
| | - Mujahed Abualfoul
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Dallas, TX 75203, United States
| | - Robert Chilton
- Department of Internal Medicine, Methodist Dallas Medical Center, Dallas, TX 75203, United States
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Ishizu M, Mori H, Ohishi M, Kuroda A, Akehi Y, Yoshida S, Aihara KI, Aiba M, Kawano T, Hashida S, Matsuhisa M. Urinary adiponectin excretion is an early predictive marker of the decline of the renal function in patients with diabetes mellitus. J Diabetes Complications 2021; 35:107848. [PMID: 33558151 DOI: 10.1016/j.jdiacomp.2021.107848] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 12/07/2020] [Accepted: 12/30/2020] [Indexed: 01/17/2023]
Abstract
AIMS Since diabetes-associated kidney complication changes from diabetic nephropathy to diabetic kidney disease (DKD), more suitable biomarkers than urinary albumin are required. It has been hypothesized that urinary adiponectin (u-ADPN) is associated with the progression of DKD. We therefore evaluated the effectiveness of u-ADPN in predicting the decline of the renal function in patients with diabetes prior to end-stage renal disease. METHODS An ultrasensitive immune complex transfer enzyme immunoassay (ICT-EIA) was used to measure total and high molecular weight (HMW) adiponectin separately. We evaluated the relationships between the creatinine-adjusted urinary total-ADPN and HMW-ADPN, albumin (UACR) and liver-type fatty acid binding protein (L-FABP) at baseline and the 2-year change of the estimated glomerular filtration rate (ΔeGFR). RESULTS This 2-year prospective observational study included 201 patients with diabetes. These patients were divided into three groups according to their ΔeGFR: ≤-10 mL/min/1.73m2, >-10 and ≤0 mL/min/1.73m2, and >0 mL/min/1.73m2. Jonckheere-Terpstra test showed that lower ΔeGFR was associated with higher u-HMW-ADPN (p = 0.045). In logistic regression analysis, u-HMW-ADPN was associated with ΔeGFR after adjusted age, sex, and basal eGFR. CONCLUSION Urinary HMW-ADPN could predict a declining renal function in patients with diabetes.
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Affiliation(s)
- Masashi Ishizu
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | - Hiroyasu Mori
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | - Mami Ohishi
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | - Akio Kuroda
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | - Yuko Akehi
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | - Sumiko Yoshida
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Ken-Ichi Aihara
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Motohiro Aiba
- Life Style Diseases, Institute for Health Sciences, Tokushima Bunri University, Tokushima, Japan
| | - Tomoharu Kawano
- Human Life Science, Tokushima Bunri University, Tokushima, Japan
| | - Seiichi Hashida
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Munehide Matsuhisa
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
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Xu R, Cai H, Fan Z, Wan Y, Gao X. The change in kidney function was associated with carotid artery plaque in a community-based population: A cohort study. Nutr Metab Cardiovasc Dis 2021; 31:119-126. [PMID: 32994120 DOI: 10.1016/j.numecd.2020.08.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 08/09/2020] [Accepted: 08/11/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND AND AIMS We performed the current study to evaluate the association between dynamic change in estimated glomerular filtration rate (eGFR) and the risk of carotid artery plaque (CAP) in a community-based population. METHODS AND RESULTS A total number of 37,093 Chinese adults (21,790 men and 15,303 women, aged 42.6 ± 11.6 years) free of chronic kidney diseases were enrolled. The change in eGFR was calculated based on two measurements in 2013 and 2014 (mean interval: 1.2 y). Participants were further classified into three groups based on the change in eGFR: fast-decrease (<-3.3%), stable (from -3.3% to 3.3%), and fast-increase (≥3.3%). CAP was annually assessed by ultrasound B model throughout the study (2013-2018). We have identified 1,624 new cases of CAP (16.0 per 1000 person-year) during follow up. Compared to participants with stable eGFR, participants in both fast-decrease and fast-increase groups were associated with 1.99 folds (HR = 1.99, 95% CI: 1.54, 2.57) and 3.15 folds (HR = 3.15, 95% CI: 2.38, 4.16) higher likelihood of developing CAP. The association between continuous change in eGFR and the risk of CAP demonstrate a "U" shape. Sensitivity analysis generated similar results with main analysis. CONCLUSIONS Both fast decrease and increase in eGFR were associated with the risk of developing CAP in Chinese adults.
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Affiliation(s)
- Renying Xu
- Department of Clinical Nutrition, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
| | - Hong Cai
- Department of Nephrology, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhuping Fan
- Department of Health Management Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yanping Wan
- Department of Clinical Nutrition, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Xiang Gao
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA
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Ahmed SB, Dumanski SM. Why Do Patients With Well-Controlled Vascular Risk Factors Develop Progressive Chronic Kidney Disease? Can J Cardiol 2019; 35:1170-1180. [DOI: 10.1016/j.cjca.2019.06.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 06/07/2019] [Accepted: 06/14/2019] [Indexed: 01/17/2023] Open
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