medwireNews: Higher expression of the glucagon-like peptide (GLP)-1 receptor gene, measured as a proxy for GLP-1 receptor agonist use, is associated with a reduced risk for kidney disease progression, US research shows.
“These findings support pleiotropic nephroprotective mechanisms of GLP-1 [receptor agonists] independent of their effects on body weight and glycemic control,” write Adriana Hung (Vanderbilt University Medical Center, Nashville, Tennessee) and co-authors in JAMA Network Open.
They explain that previous studies have demonstrated that GLP-1 receptor agonists reduce kidney disease progression in people with diabetes, but the efficacy in broader populations is unclear.
“The effect of genetic variants that influence GLP-1 receptor gene (GLP1R) expression may serve as a proxy for GLP-1 [receptor agonist] treatment, providing a detailed assessment of its effects on kidney function in different clinical contexts,” the researchers remark.
To test this hypothesis, they carried out a genetic association study among 353,153 individuals (median age 66 years, 92.5% men) from the US Department of Veterans Affairs Million Veteran Program. Of these, 25.7% had diabetes and 45.0% had obesity.
The researchers report that during a median 5.1 years of follow-up, 4.6% of the cohort experienced kidney disease progression, defined as a composite of incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate.
Overall, higher genetic GLP1R expression, determined by a genetic risk score based on genetic variants associated with GLP1R mRNA levels across various tissue samples, was associated with a reduced risk for kidney disease progression.
Specifically, individuals with a genetic risk score for GLP1R expression in the top tertile had a significant 4% lower risk for kidney disease progression than those with scores in the bottom tertile, after adjusting for age, sex, baseline kidney function, blood pressure, BMI, use of an angiotensin-converting enzyme or angiotensin II receptor blocker, and the presence or absence of diabetes.
Subgroup analyses stratified by diabetes or obesity status showed similar results and there was no interaction between GLP1R genetic risk score and either diabetes or overweight or obesity. This indicates that “the association of higher GLP1R expression with lower risk of kidney disease progression was consistent across subgroups,” say Hung et al.
They conclude: “Although larger sample sizes would be needed to detect statistically significant effects in these subgroups, our findings warrant further investigation and support the potential for broader clinical applications of GLP-1 [receptor agonists].”
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