Arterial Stiffness and Kidney Function: A Mendelian Randomization Study

Abstract

Background and Aims: Although observational studies have suggested that arterial stiffness is associated with kidney function decline, the causal nature remains unclear. We aimed to determine the potential causal relationship between arterial stiffness and kidney function using a two-sample Mendelian randomization study. Methods: We used four single nucleotide polymorphisms (SNPs) as instrumental variables for carotid-femoral pulse wave velocity (PWV). Multiple Mendelian randomization methods were performed in this study, including inverse-variance weighted method, weighted median-based method and MR-Egger method. Results: The results showed genetically instrumented higher arterial stiffness was associated with lower estimated glomerular filtration rate (eGFR) (beta, -0.007, 95% CI: -0.011 to -0.002, p = 0.002), whereas not associated with the risk of CKD (odds ratio, 1.027, 95% CI: 0.863 to 1.097, p = 0.821) or BUN (beta, -0.012, 95% CI: -0.023 to 0.001, p = 0.032). Conclusions: Our findings suggest a causal relationship between arterial stiffness and eGFR. However, we did not find evidence of a causal association between arterial stiffness and risk of CKD or blood urea nitrogen. Novel therapeutic approaches to reduce arterial stiffness should be developed for kidney protection. Funding Statement: The study was supported by grants from the Peking University Start-up Grant (BMU2018YJ002), High-performance Computing Platform of Peking University and Beijing Technology and Business University Grant: 88442Y0033. Declaration of Interests: The authors declare that they have no relevant financial interests. Ethics Approval Statement: Informed consent was obtained from all participants and ethical approval was received from respective institutional review boards of each contributing study.