Causal association between cytokines and chronic kidney disease based on Mendelian randomization

Objective Cytokines have been considered closely related to the development of chronic kidney disease(CKD), and this study explored the causal relationship between the two by Mendelian randomization (MR) method.Methods The research data were obtained from genome wide association study (GWAS), and genetic loci that were independent of each other and related to cytokines and CKD were selected as instrumental variables(IVs).The primary approach utilized in the MR analysis was the inverse variance weighted (IVW) method, complemented by the weighted median and MR-Egger regression methods.The sensitivity analysis were conducted using Cochran’s Q tests, leave-one-out analysis, and MR-Egger intercept tests.Results The IVW analysis method is mainly used, and the Benjamin Hochberg (BH) method is used for correction.When p＜0.00055(0.05/91),the results are significantly causal;when 0.00055≤p＜0.05,the results are potentially causal.A total of 11 inflammatory factors were found to be significantly or potentially associated with CKD.There were 5 positively associated with CKD, among which IL-17C(IVW: p=1.426*10-4, OR:1.171, 95%CI: 1.079-1.270) was significantly associated,and the potentially associated were IL-17A, CXCL10, MCP-4, and DNER.There were 6 negatively associated with CKD, among which FGF5(IVW:p=8.282*10-8,OR:0.909, 95%CI:0.878-0.941) was significantly correlated,and the potentially associated were FGF21,IL-10,CD40R,CD244,and OPG.The accuracy and robustness of the findings were confirmed using sensitivity tests.Conclusion IL-17C,IL-17A,CXCL10,MCP-4,and DNER may increase the risk of CKD,with IL-17C being the most significant;FGF5,FGF21,IL-10,CD40R,CD244,and OPG may decrease the risk of CKD,with FGF5 being the most significant.