Unraveling the causal link between inflammatory cytokines and hypertensive renal disease: a Mendelian randomization analysis

Purpose
Hypertensive renal disease is a primary contributor to morbidity and death, with inflammation serving a crucial role in its development. Elevated levels of inflammatory cytokines are frequently observed in hypertensive renal disease patients; however, their causal relationship with the disease remains unclear.

Methods
A two-sample Mendelian randomization (MR) analysis was conducted using genetic variants associated with inflammatory cytokine levels obtained from genome-wide association studies (GWAS) of 14,824 healthy participants. Summary statistics for hypertensive renal disease were derived from the FinnGen R10 dataset. The inverse variance weighted (IVW) method was the primary approach for assessing causal effects, complemented by multiple sensitivity analyses to ensure robustness of the findings.

Results
In the bidirectional MR analysis, the IVW analysis identified two inflammatory cytokines as risk factors for hypertensive renal disease: interferon-gamma levels (OR 1.500, 95% CI 1.130–1.992) and oncostatin-M levels (OR 1.414, 95% CI 1.086–1.841). Additionally, the study identified three cytokines as protective factors against hypertensive renal disease: CD40L receptor levels (OR 0.817, 95% CI 0.679–0.983), interleukin-10 receptor subunit beta levels (OR 0.829, 95% CI 0.703–0.976), and interleukin-20 receptor subunit alpha levels (OR 0.725, 95% CI 0.549–0.957). These results highlight the complex role of inflammatory cytokines in the progression of hypertensive renal disease. No evidence of horizontal pleiotropy, heterogeneity, or reverse causality was found in the above results.

Conclusion
This Mendelian randomization analysis identified inflammatory cytokines associated with hypertensive renal disease, providing a foundation for future mechanistic research and potential therapeutic targets.