Renal failure · 2025
Glucagon-like peptide-1 receptor agonists, inflammation, and kidney diseases: evidence from Mendelian randomization.
СтатьяМетаанализНазвание и аннотация: Перевод в очереди
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Yao Yu-Xuan, Tang Chen, Si Feng-Lei, Lv Ji-Cheng, Shi Su-Fang, Zhou Xu-Jie, Liu Li-Jun, Zhang Hong
Аннотация
OBJECTIVE: It has been proved that glucagon-like peptide-1 receptor (GLP1R) agonists have positive effects on renal outcomes in diabetic patients. However, it remains unknown whether GLP1R agonists could provide similar protection against other kidney diseases.
METHODS: We performed two-sample Mendelian randomization (MR) analyses to determine the causal effects of GLP1R agonists on multiple kidney diseases. Exposure to GLP1R agonist was proxied by the available cis-eQTLs for GLP1R. Primary outcomes included the risk assessment for diabetic nephropathy, IgA nephropathy, membranous nephropathy, nephrotic syndrome, chronic kidney disease, acute glomerulonephritis, chronic glomerulonephritis and calculus of kidney/ureter. Type 2 diabetes and body mass index were used as positive control. Two-stage network MR analyses were conducted to assess the mediation effect of inflammatory proteins on the relationships between GLP1R agonists and kidney diseases.
RESULTS: After meta-analyses of both discovery and validation cohorts, genetically proxied GLP1R agonist was found to significantly associated with a decreased risk of diabetic nephropathy (OR = 0.72, 95%CI = 0.54-0.97, p = 0.031) and IgA nephropathy (OR = 0.58, 95%CI = 0.36-0.94, p = 0.027). Two-stage network MR revealed that there was an indirect effect of GLP1R agonist on IgA nephropathy through signaling lymphocytic activation molecule family member 1 (SLAMF1), with a mediated proportion of 34.27% (95% CI, 1.47-67.03%, p = 0.041) of the total effect.
CONCLUSIONS: The findings of current study presented genetic proof for the potential protective effects of GLP1R agonists in the development of diabetic nephropathy and IgA nephropathy, offering a novel sight for future mechanistic and clinical applications.
METHODS: We performed two-sample Mendelian randomization (MR) analyses to determine the causal effects of GLP1R agonists on multiple kidney diseases. Exposure to GLP1R agonist was proxied by the available cis-eQTLs for GLP1R. Primary outcomes included the risk assessment for diabetic nephropathy, IgA nephropathy, membranous nephropathy, nephrotic syndrome, chronic kidney disease, acute glomerulonephritis, chronic glomerulonephritis and calculus of kidney/ureter. Type 2 diabetes and body mass index were used as positive control. Two-stage network MR analyses were conducted to assess the mediation effect of inflammatory proteins on the relationships between GLP1R agonists and kidney diseases.
RESULTS: After meta-analyses of both discovery and validation cohorts, genetically proxied GLP1R agonist was found to significantly associated with a decreased risk of diabetic nephropathy (OR = 0.72, 95%CI = 0.54-0.97, p = 0.031) and IgA nephropathy (OR = 0.58, 95%CI = 0.36-0.94, p = 0.027). Two-stage network MR revealed that there was an indirect effect of GLP1R agonist on IgA nephropathy through signaling lymphocytic activation molecule family member 1 (SLAMF1), with a mediated proportion of 34.27% (95% CI, 1.47-67.03%, p = 0.041) of the total effect.
CONCLUSIONS: The findings of current study presented genetic proof for the potential protective effects of GLP1R agonists in the development of diabetic nephropathy and IgA nephropathy, offering a novel sight for future mechanistic and clinical applications.