Abstract: Objective To explore the causal relationship between cytokines and chronic kidney disease(CKD)using the Mendelian randomization(MR)analysis. Methods Data for the analysis were sourced from genome-wide association studies(GWAS)and independent genetic loci associated with cytokines were selected as instrumental variables(IVs). MR analysis was conducted primarily using the inverse variance weighted(IVW)method, complemented by the Weighted Median and MR Egger regression approaches. Sensitivity analysis was performed using MR Egger regression intercept term test, leave-one-out analysis, and Cochrans Q tests. The Bonferroni correction was applied and the results were considered significantly causal when P<0.055×10^-2(0.050/91), and potentially causal when 0.055×10^-2≤P<0.050. Results A total of 10 inflammatory factors were identified as significantly or potentially associated with CKD. Six cytokines showed positive causal associations with CKD, with IL-17C being significantly associated(for IVW, OR=1.171, 95%CI: 1.079-1.270, P=1.426×10^-4). Cytokines potentially associated with increased risk of CKD included IL-17A, CXCL10, MCP-4, DNER, and CCL-4. Four cytokines demonstrated negative causal associations with CKD, although none were significantly correlated. CD40R, CD244, OPG, and MIP-1a were potentially associated with a reduced risk of CKD included. The precision and robustness of the findings were confirmed by sensitivity tests. Conclusion IL-17C significantly increases the risk of CKD, while IL-17A, CXCL10, MCP-4, DNER and CCL-4 may increase the risk of CKD. In contrast, CD40R, CD244, OPG, and MIP-1a may lower the risk of CKD.

Key words: Chronic kidney disease, Cytokines, Mendelian randomization, Causal inference, Drug target