GLP1R Gene Expression and Kidney Disease Progression.

Autor:	Triozzi JL; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Yu Z; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Giri A; Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, Tennessee.; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Chen HC; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Wilson OD; Nashville VA Medical Center, VA Tennessee Valley Healthcare System, Nashville., Ferolito B; Million Veteran Program Coordinating Center, VA Boston Healthcare System, Boston, Massachusetts., Ikizler TA; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Akwo EA; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Robinson-Cohen C; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Gaziano JM; Million Veteran Program Coordinating Center, VA Boston Healthcare System, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital and Harvard School of Medicine, Boston, Massachusetts., Cho K; Million Veteran Program Coordinating Center, VA Boston Healthcare System, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital and Harvard School of Medicine, Boston, Massachusetts., Phillips LS; VA Atlanta Health Care System, Decatur, Georgia.; Division of Endocrinology and Metabolism, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia., Tao R; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee., Pereira AC; Million Veteran Program Coordinating Center, VA Boston Healthcare System, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital and Harvard School of Medicine, Boston, Massachusetts., Hung AM; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.; Nashville VA Medical Center, VA Tennessee Valley Healthcare System, Nashville.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2024 Oct 01; Vol. 7 (10), pp. e2440286. Date of Electronic Publication: 2024 Oct 01.
DOI:	10.1001/jamanetworkopen.2024.40286
Abstrakt:	Importance: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have nephroprotective properties beyond those related to weight loss and glycemic control. Objective: To investigate the association of genetically proxied GLP-1RAs with kidney disease progression. Design, Setting, and Participants: This genetic association study assembled a national retrospective cohort of veterans aged 18 years or older from the US Department of Veterans Affairs Million Veteran Program between January 10, 2011, and December 31, 2021. Data were analyzed from November 2023 to February 2024. Exposures: Genetic risk score for systemic GLP1R gene expression that was calculated for each study participant based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the Genotype-Tissue Expression project. Main Outcomes and Measures: The primary composite outcome was incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate. Cox proportional hazards regression survival analysis assessed the association between genetically proxied GLP-1RAs and kidney disease progression. Results: Among 353 153 individuals (92.5% men), median age was 66 years (IQR, 58.0-72.0 years) and median follow-up was 5.1 years (IQR, 3.1-7.2 years). Overall, 25.7% had diabetes, and 45.0% had obesity. A total of 4.6% experienced kidney disease progression. Overall, higher genetic GLP1R gene expression was associated with a lower risk of kidney disease progression in the unadjusted model (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99; P = .02) and in the fully adjusted model accounting for baseline patient characteristics, body mass index, and the presence or absence of diabetes (HR, 0.96; 95% CI, 0.92-1.00; P = .04). The results were similar in sensitivity analyses stratified by diabetes or obesity status. Conclusions and Relevance: In this genetic association study, higher GLP1R gene expression was associated with a small reduction in risk of kidney disease progression. These findings support pleiotropic nephroprotective mechanisms of GLP-1RAs independent of their effects on body weight and glycemic control.
Databáze:	MEDLINE
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