Kidney Function and Blood Pressure: A Bi-directional Mendelian Randomisation Study

Abstract

ObjectiveTo evaluate the bi-directional causal relation between kidney function and blood pressure. DesignMendelian randomisation study. SettingWe performed two-sample Mendelian randomisation analyses. Genetic instruments of kidney function traits were selected from summary statistics of genome-wide association studies (GWAS) of glomerular filtration rate estimated from serum creatinine (eGFRcr) and blood urea nitrogen (BUN) and were required to be associated with both eGFRcr and BUN to ensure that the instruments were more likely to represent the underlying kidney function. Genetic instruments of blood pressure were selected from summary statistics of GWAS of systolic and diastolic blood pressure. We investigated Mendelian randomisation hypothesis using several alternative approaches, including methods that are most robust to the presence of horizontal pleiotropy. ParticipantsThe summary statistics of eGFRcr included 567,460 participants from 54 cohorts, and the summary statistics of BUN included 243,031 participants from 48 cohorts from the Chronic Kidney Disease Genetics (CKDGen) Consortium. The summary statistics of systolic and diastolic blood pressure included 757,601 participants from the UK Biobank and 78 cohorts from the International Consortium for Blood Pressure (ICBP). ResultsSignificant evidence supported the causal effects of higher kidney function on lower blood pressure with multiple methods. Based on the mode-based Mendelian randomisation analysis approach, known for its robustness to the presence of pleiotropic effect, the effect estimate for 1 SD higher in eGFRcr was -0.17 SD unit (95 % CI: -0.09 to -0.24) in systolic blood pressure (SBP) and -0.15 SD unit (95% CI: -0.07 to -0.22) in diastolic blood pressure (DBP). In contrast, the causal effects of blood pressure on kidney function were not statistically significant. ConclusionsMendelian randomisation analyses support causal effects of higher kidney function on lower blood pressure. These results suggest preventing kidney function decline can reduce the public health burden of hypertension.