Bidirectional Mendelian randomization analysis of the causal associations between serum vitamin D levels and multiple kidney diseases

Abstract

Abstract The relationship between vitamin D levels and the risk of kidney diseases, such as IgA nephropathy (IgAN), membranous nephropathy (MN), and diabetic nephropathy (DN), is still debated in observational studies. This research aims to evaluate the causal relationships between vitamin D and these kidney diseases using a bidirectional Mendelian randomization (MR) approach. We obtained summary-level data from genome-wide association studies (GWAS) on serum 25(OH)D levels, IgAN, MN, and DN to assess the causal impact of vitamin D on these kidney diseases. The primary method used for MR analysis was the inverse variance weighted (IVW) approach. To further ascertain the stability and reliability of our results, we performed sensitivity analyses including Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis, which helped identify potential pleiotropy and outlier single nucleotide polymorphisms (SNPs) influencing the associations. Our analysis revealed no causal relationships between serum 25(OH)D levels and the risks of IgAN, MN, and DN. Sensitivity analyses confirmed the robustness of the MR findings. This MR analysis robustly refutes causal associations between genetically determined 25(OH)D levels and IgAN, MN, and DN. These null findings challenge the paradigm of vitamin D supplementation as a preventive strategy for these nephropathies, urging clinicians to prioritize interventions targeting modifiable risk factors over vitamin D optimization in kidney disease management.