Estimating the Causal Relationship Between Glomerular Filtration Rate and Cardiovascular Disease: A Mendelian Randomization Study

Abstract BACKGROUND A large number of observational studies have now shown that a decrease in the estimated glomerular filtration rate (eGFR) is associated with an increased risk of cardiovascular disease. However, there are no uniform conclusions regarding the potential relationship between the estimated glomerular filtration rate and cardiovascular disease. We will explore the causal relationship between estimated glomerular filtration rate and cardiovascular disease for the first time using a two-sample Mendelian randomization analysis. METHODS We first identified genetic tools for estimating glomerular filtration rate from a genome-wide association study (GWAS). We performed a two-sample analysis of different cardiovascular outcome events using MR analysis with inverse variance weighting, weighted median, MR- PRESSO, MR- Egger, and leave-one-out methods. RESULTS The findings showed weak evidence of a potential causal relationship between reduced estimated glomerular filtration rate and heart failure (HF), with IVW results suggesting critical statistical significance (OR = 1.009,95%CI = 1.003–1.015, p = 0.003). In estimating glomerular filtration rate and coronary artery disease (CAD) (OR = 1.006,95%CI = 0.998–1.013, p = 0.14), estimated glomerular filtration rate and cardiovascular disease (CVD) (OR = 1.003,95%CI = 0.995–1.011, p = 0.45), estimating glomerular filtration rate and stroke (OR = 1.000, 95%CI = 0.9998–1.0001, p = 0.95) and estimated glomerular filtration rate and atrial fibrillation (AF) (OR = 1.004, 95% CI = 0.9952–1.0126, p = 0.38) the results of the IVW trial did not suggest a potential causal relationship between eGFR and cardiovascular outcome events. CONCLUSION Multiple large MR analyses we performed found a weak causal association between estimated glomerular filtration rate and the risk of heart failure, but we did not find a significant causal association of estimated glomerular filtration rate for other cardiovascular outcome events (stroke, CVD, atrial fibrillation, coronary artery disease).