Kidney function and cardiovascular diseases: a large-scale observational and Mendelian randomization study

Abstract

BackgroundPrior observational studies have found an association between kidney function and cardiovascular diseases (CVDs). However, these studies did not investigate causality. Therefore, the aim of this study is to examine the causal relationship between kidney function and CVDs.MethodsWe utilized data from the eICU Collaborative Research Database (eICU-CRD) from the years 2014-2015 to evaluate the observational association between renal failure (RF) and CVDs. To investigate the causal effects of kidney function (estimated glomerular filtration rate [eGFR] and chronic kidney disease [CKD]) and CVDs (including atrial fibrillation [AF], coronary artery disease [CAD], heart failure [HF], any stroke [AS], and any ischemic stroke [AIS]), we conducted a two-sample bidirectional Mendelian randomization (MR) analysis.ResultsIn the observational analysis, a total of 157,883 patients were included. After adjusting for potential confounding factors, there was no significant association between baseline RF and an increased risk of developing CVDs during hospitalization [adjusted odds ratio (OR): 1.056, 95% confidence interval (CI): 0.993 to 1.123, P = 0.083]. Conversely, baseline CVDs was significantly associated with an increased risk of developing RF during hospitalization (adjusted OR: 1.189, 95% CI: 1.139 to 1.240, P < 0.001). In the MR analysis, genetically predicted AF was associated with an increased risk of CKD (OR: 1.050, 95% CI: 1.016 to 1.085, P = 0.004). HF was correlated with lower eGFR (β: -0.056, 95% CI: -0.090 to -0.022, P = 0.001). A genetic susceptibility for AS and AIS was linked to lower eGFR (β: -0.057, 95% CI: -0.079 to -0.036, P < 0.001; β: -0.029, 95% CI: -0.050 to -0.009, P = 0.005; respectively) and a higher risk of CKD (OR: 1.332, 95% CI: 1.162 to 1.528, P < 0.001; OR: 1.197, 95% CI: 1.023 to 1.400, P = 0.025; respectively). Regarding the reverse direction analysis, there was insufficient evidence to prove the causal effects of kidney function on CVDs. Outcomes remained consistent in sensitivity analyses.ConclusionOur study provides evidence for causal effects of CVDs on kidney function. However, the evidence to support the causal effects of kidney function on CVDs is currently insufficient. Further mechanistic studies are required to determine the causality.