The causal relationship between circulating leukocytes and kidney function: A Mendelian randomization study

Abstract

Background Several studies proposed that inflammatory response strongly correlated with kidney function and the progression of the chronic kidney disease (CKD), both in terms of its onset and course as well as any ensuing consequences. Objectives To investigate the potential causal relationship of the five subtypes of leukocytes count (monocytes, lymphocytes, neutrophils, eosinophils, and basophils) with CKD and kidney function by employing Mendelian randomization (MR) analysis. Methods At the genome-wide significance level, single-nucleotide polymorphisms correlated to major white blood cell types were identified. Large-scale genome-wide association studies with sample sizes of 44,266, 86,640, 58,284, and 23,210 provided summary-level data for CKD, eGFR, and urine albumin-to-creatinine ratio (uACR), respectively. The inverse variance weighted (IVW) method was used for primary MR analysis, and additional sensitivity approach were carried out to evaluate the robustness. Results We discovered that a higher genetically determined monocyte count was causally associated with an increased genetically predicted eGFR level (beta = 0.0035; 95% CI: 0.0013–0.0057; P = 1.45×10− 3) and uACR level (betaIVW = 0.017; 95%CI: 0.008–0.027, P = 5.5 × 10− 4). Sensitivity analyses employing different approaches revealed comparable associations, while MR-Egger regression revealed no indication of pleiotropy. In addition, we observed that was lymphocyte count (betaIVW = 0.018; 95%CI: 0.004–0.033, P = 1.1 × 10− 2) and neutrophil count (betaIVW = 0.018; 95%CI: 0.001–0.035, P = 3.9 × 10− 2) were positively associated with uACR, while the association remained non-significant after Bonferroni correction. Conclusion Our research implicates peripheral white blood cells, specifically monocytes, lymphocytes, and eosinophils, to the kidney function damage, underscoring the necessity for mechanistic investigations to discover these associations.