The causal relationship between biological function of mitochondria and chronic kidney disease： a Mendelian randomization study

ObjectiveTo investigate the causal relationship between mitochondrial functional proteins and chronic kidney disease （CKD） using Mendelian randomization analysis， thus providing a genetic reference for the early prevention of CKD.MethodsPublicly accessible GWAS data were collected and used to analyze the causal relationship between mitochondrial functional proteins and CKD， with inverse variance weighted analysis as the core method. Additionally， heterogeneity and horizontal pleiotropy tests were performed， and the stability of the results was assessed using the leave-one-out method.ResultsA total of 70 mitochondrial functional proteins were included in this analysis. The results of the inverse-variance weighted analysis showed that increased levels of NDUFB8 （<italic>P</italic>=0.023， <italic>OR</italic>=1.142）， MRPL52 （<italic>P</italic>=0.016， <italic>OR</italic>=1.101）， COX4i2 （<italic>P</italic>=0.027， <italic>OR</italic>=1.079）， and COX8A （<italic>P</italic>=0.032， <italic>OR</italic>=1.062） were associated with an increased risk of CKD， while increased levels of RRF （<italic>P</italic>=0.007， <italic>OR</italic>=0.899） and DIABLO （<italic>P</italic>=0.009， <italic>OR</italic>=0.887） were related to a reduced risk of CKD. Regression analysis demonstrated that the included single-nucleotide polymorphisms （SNPs） did not exhibit pleiotropy （<italic>P</italic>&gt;0.05）. The leave-one-out analysis results also confirmed the stability and reliability of the study findings.ConclusionThis study provides new evidence to elucidate the roles of NDUFB8， RRF， MRPL52， COX4i2， COX8A and DIABLO in the pathophysiology of CKD. These findings may be of significant importance for understanding the pathogenesis of CKD， identifying new therapeutic targets， and developing effective treatment strategies.