Genetically proxied GLP1R agonist is associated with a decreased risk of diabetic nephropathy ( = 0.72) and IgA nephropathy (OR = 0.58).
GLP1R agonists may reduce the risk of diabetic nephropathy and IgA nephropathy based on genetic evidence.
The odds ratio for diabetic nephropathy suggests a significant association with a decreased risk.
For IgA nephropathy, a similar significant decrease in risk was observed.
An indirect effect of GLP1R agonists on IgA nephropathy was identified through a specific immune signaling pathway.
The mediated proportion of this indirect effect was 34.27%, indicating a notable relationship.
Simplified
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 (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 ( = 0.72, 95%CI = 0.54-0.97, = 0.031) and IgA nephropathy (OR = 0.58, 95%CI = 0.36-0.94, = 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%, = 0.041) of the total effect. p p p
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.
Key numbers
0.72
Decrease in Risk
from meta-analysis of discovery and validation cohorts.
0.58
Decrease in Risk
from meta-analysis of discovery and validation cohorts.
34.27%
Mediated Proportion by
Proportion of total effect mediated by .
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