Su Jiaming, Hu Jiyuan, Liu Hongfang, Guo Yan, Shi Yang, Zheng Yicheng, Dong Zhaoxi, Liu Jiayou, Xu Zheyu, Yu Xinhui, Mei Jie, Peng Jing, Wang Lin, Liu Qingqing
Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
Department of Endocrinology and Nephrology, Renal Research Institute of Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
Diabetol Metab Syndr. 2025 Jun 11;17(1):205. doi: 10.1186/s13098-025-01764-y.
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).
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.
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.
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.
本研究旨在利用孟德尔随机化（MR）技术确定血浆脂质组与慢性肾脏病（CKD）发生及进展之间的因果关系。
从已发表的大规模全基因组关联研究中检索179种脂质种类和六种CKD相关表型的汇总统计数据。使用逆方差加权（IVW）作为主要的MR方法进行双向两样本MR分析。采用Cochrane's Q检验、MR-Egger截距分析和MR-PRESSO评估异质性和水平多效性。应用留一法检验以确保MR结果的稳定性，并采用Benjamini-Hochberg（BH）校正来评估因果关系的稳健性。
通过结合MR和敏感性分析的见解，本研究揭示了33种血浆脂质水平与各种CKD相关结局之间的显著关联。各种血浆脂质种类被确定与肾脏疾病存在正或负的因果联系，IVW-OR值的特定范围表明了这一点（所有P < 0.05）。经过BH校正后，升高的甾醇酯（27:1/18:2）水平（OR：1.
