The association between immune cells and acute kidney injury: insights from Mendelian randomization

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. 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. 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. 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.

免疫紊乱是急性肾损伤（acute kidney injury, AKI）的显著特征。然而，不同免疫细胞表型在急性肾损伤发病机制中的具体作用仍不甚明确。本研究旨在探讨731种免疫细胞表型与急性肾损伤的相关性。我们从全基因组关联研究目录（GWAS Catalog）及开放全基因组关联研究（Open GWAS）数据库中获取了731种免疫细胞表型的数据，并开展了一系列质量控制流程，以筛选与暴露相关的工具变量（instrumental variables, IV）。我们从Finngen R11及CKDGen数据库中获取了急性肾衰竭（acute renal failure, ARF）与肾功能快速下降的相关数据作为结局指标。随后，我们采用逆方差加权法开展了两样本孟德尔随机化（two-sample Mendelian randomization, MR）分析，在基因层面探究731种免疫细胞特征与急性肾衰竭及肾功能快速下降之间的因果关联。我们开展了敏感性分析，涵盖留一法（leave-one-out）及其他孟德尔随机化分析模型。在邦费罗尼校正后的显著性水平下，共9种免疫细胞表型（包括IgD+CD24- B细胞表面的CD25）与急性肾衰竭相关；4种免疫细胞表型（包括浆细胞样树突状细胞的SSC-A）与肾功能快速下降相关。敏感性分析结果显示本研究结论具有稳健性。本研究通过遗传学分析证实了特定免疫细胞类型与急性肾损伤之间存在显著因果关联，为后续临床研究提供了重要参考。