Abstract
OBJECTIVE: This study aimed to utilize Mendelian randomization (MR) techniques to determine causal relationships between the plasma lipidome and the occurrence and progression of chronic kidney disease (CKD). METHODS: Summary statistics for 179 lipid species and six CKD-related phenotypes were retrieved from published large-scale genome-wide association studies. A bidirectional two-sample MR analysis was performed using the inverse-variance weighting (IVW) as the primary MR method. Cochrane's Q test, the MR‒Egger intercept analysis, and the MR-PRESSO were employed to evaluate heterogeneity and horizontal pleiotropy. The leave-one-out test was applied to ensure the stability of the MR findings, and Benjamini‒Hochberg (BH) correction was utilized to assess the robustness of causal links. RESULTS: This study unveiled significant associations between 33 plasma lipid levels and various CKD-related outcomes by combining insights from both MR and sensitivity analyses. Various plasma lipid species were identified as having either positive or negative causal connections with kidney conditions, demonstrated by specific ranges of IVW-OR values (all P < 0.05). Following the BH correction, elevated sterol ester (27:1/18:2) levels (OR: 1.012 ~ 1.037, P < 0.05) and reduced phosphatidylcholine (16:1_20:4) levels (OR: 0.954 ~ 0.985, P < 0.05) consistently showed a strong causal relationship with increased urine albumin-creatinine ratio. These findings were robust across all sensitivity analyses. CONCLUSION: This study revealed potential causal associations between specific types of lipidome other than conventional lipids and the occurrence and progression of CKD. These insights pave the way for the development of early diagnostic and prophylactic CKD interventions.