Department of Urology and Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, China.
Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, the First Hospital of Jilin University, Changchun, Jilin Province, China.
Ren Fail. 2024 Dec;46(1):2319712. doi: 10.1080/0886022X.2024.2319712. Epub 2024 Mar 4.
Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD.
Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment.
Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function.
This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.
慢性肾脏病（CKD）是一种受遗传和环境因素影响的疾病，一直是广泛研究的焦点。利用孟德尔随机化，研究人员开始理清 CKD 背后复杂的因果关系。本综述深入探讨了 MR 在肾脏病学领域应用的进展和挑战，从简单总结其原理和局限性，转变为更细致地探讨其对我们理解 CKD 的贡献。
最近研究的主要发现对我们理解 CKD 产生了重大影响。值得注意的是，有证据表明，睾酮水平升高可能会损害肾功能，而较高的性激素结合球蛋白（SHBG）水平似乎具有保护作用，主要在男性中。令人惊讶的是，血浆葡萄糖和糖化血红蛋白水平的变化似乎不受遗传诱导的肾小球滤过率（eGFR）变化的影响，这表明存在独立的肾功能损害途径。
此外，生活方式因素，如身体活动和社会经济地位，成为 CKD 风险和肾脏健康的重要影响因素。睡眠时间与 CKD 之间的关系很复杂；睡眠时间短与风险增加有关，而睡眠时间长则没有明显的因果关系。此外，生活方式因素，包括饮食、运动和心理健康活动，对肾脏健康起着至关重要的作用。新的研究结果还揭示了中枢性肥胖和全身性肥胖与 CKD 发病之间存在实质性的因果关系，而遗传修饰的 LDL 胆固醇或甘油三酯水平与肾功能之间没有显著关联。
本综述不仅介绍了 MR 在 CKD 研究中的最新成果，还展望了未来的研究方向，强调了该领域关键的未解决问题。
