Immunopheno types, acute kidney injury, rapid kidney function decline, mendelian randomization analysis, genetic analyses, Diseases of the genitourinary system. Urology, RC870-923

Background Immune disorder is a prominent feature of acute kidney injury (AKI). However, the specific role of different immune cell phenotypes in the pathogenesis of AKI remains poorly understood. The aim of this study was to investigate the relevance of 731 immune phenotypes to AKI.Materials and Methods We obtained data on 731 immune cell phenotypes from the GWAS Catalog and Open GWAS databases and undertook a series of quality control measures to identify exposure-related instrumental variables (IV). Data on acute renal failure (ARF) and rapid kidney function decline were obtained from the Finngen R11 and CKDGen databases as an outcome. Subsequently, we performed two-sample Mendelian randomization (MR) using inverse variance weights to explore the causal relationship between 731 immune cell characteristics and ARF and rapid kidney function declineas at the gene level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed.Results At the significance level corrected by Bonferroni, 9 immune phenotypes, including CD25 on IgD + CD24- B cell, were associated with ARF; 4 immune phenotypes, including SSC-A on plasmacytoid dendritic cell, were associated with rapid kidney function decline. Sensitivity analysis indicated robust results.Conclusion Our study demonstrates a strong causal relationship between specific types of immune cells and AKI by genetic means, providing valuable insights for future clinical studies.