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Glucagon-like peptide-1 receptor agonists, inflammation, and kidney diseases: evidence from Mendelian randomization

Yu-Xuan Yao1,2,3, Chen Tang1,2,3, Feng-Lei Si1,2,3

  • 1Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.

Renal Failure
|April 15, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor (GLP1R) agonists show protective effects against diabetic nephropathy and IgA nephropathy. This genetic study provides evidence for GLP1R agonists in preventing these kidney diseases.

Area of Science:

  • Nephrology
  • Pharmacogenomics
  • Endocrinology

Background:

  • Glucagon-like peptide-1 receptor (GLP1R) agonists are known to benefit renal outcomes in diabetic patients.
  • The protective effects of GLP1R agonists against non-diabetic kidney diseases remain largely unexplored.

Purpose of the Study:

  • To investigate the causal relationship between GLP1R agonists and the risk of developing various kidney diseases using Mendelian randomization.
  • To explore potential mediating pathways, such as inflammatory proteins, in the observed associations.

Main Methods:

  • Two-sample Mendelian randomization (MR) analyses were conducted.
  • Genetic variants proxying GLP1R agonist exposure were identified using cis-eQTLs.
  • Associations with diabetic nephropathy, IgA nephropathy, and other kidney diseases were assessed.
  • Two-stage network MR was employed to examine mediation effects of inflammatory proteins.

Main Results:

  • GLP1R agonist exposure was significantly associated with a reduced risk of diabetic nephropathy (OR = 0.72) and IgA nephropathy (OR = 0.58).
  • Network MR indicated an indirect protective effect of GLP1R agonists on IgA nephropathy mediated by SLAMF1 (signaling lymphocytic activation molecule family member 1).

Conclusions:

  • This study provides genetic evidence supporting the potential renoprotective role of GLP1R agonists in diabetic nephropathy and IgA nephropathy.
  • Findings suggest novel therapeutic avenues for GLP1R agonists in managing these kidney conditions.
Keywords:
Glucagon-like peptide-1 receptor agonistsIgA nephropathyMendelian randomizationchronic kidney diseasediabetic nephropathy

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