Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of Urology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
Ren Fail. 2024 Dec;46(2):2387430. doi: 10.1080/0886022X.2024.2387430. Epub 2024 Aug 12.
Extensive researches highlight the detrimental impact of sleep disorders such as insomnia and insufficient sleep duration on kidney function. However, establishing a clear causal relationship between insomnia, sleep duration, and kidney function remains challenging. This study aims to estimate this relationship using Mendelian randomization (MR).
Independent genetic variants strongly associated with insomnia ( = 462,341) and sleep duration ( = 460,099) were selected as instrumental variables from corresponding genome-wide association studies (GWAS). Kidney function parameters, including serum creatinine, estimated glomerular filtration rate by cystatin C (eGFRcys), acute renal failure (ARF), chronic renal failure (CRF), kidney injury molecule-1, neutrophil gelatinase associated lipocalin, microalbuminuria, cystatin C, and β2 microglobulin, were derived from GWAS databases. A two-sample MR study was conducted to assess the causal relationship between sleep disorders and kidney function, and multivariable MR was used to identify potential mediators. The inverse-variance weighted was used as the primary estimate.
MR analysis found robust evidence indicating that insomnia and short sleep duration were associated with an increased risk of elevated serum creatinine, regardless of adjusting for obesity. Causal links between sleep duration and eGFRcys or cystatin C were also identified. While genetically predicted insomnia and sleep duration were found to potentially impact ARF, CRF, microalbuminuria, and β2 microglobulin, the -values in multivariable MR analysis became nonsignificant. No pleiotropy was detected.
This study demonstrates a causal impact of insomnia on the risk of elevated serum creatinine and a positive effect of sleep duration on serum creatinine, eGFRcys, and cystatin C. Our findings also suggest their potential indirect effects on ARF, CRF, microalbuminuria, and β2 microglobulin mediated by obesity.
大量研究强调了睡眠障碍（如失眠和睡眠时间不足）对肾功能的有害影响。然而，确定失眠、睡眠时间与肾功能之间的明确因果关系仍然具有挑战性。本研究旨在使用孟德尔随机化（MR）来估计这种关系。
从相应的全基因组关联研究（GWAS）中选择与失眠（ = 462,341）和睡眠时间（ = 460,099）强烈相关的独立遗传变异作为工具变量。从 GWAS 数据库中获得肾功能参数，包括血清肌酐、胱抑素 C 估计的肾小球滤过率（eGFRcys）、急性肾衰竭（ARF）、慢性肾衰竭（CRF）、肾损伤分子-1、中性粒细胞明胶酶相关脂质运载蛋白、微量白蛋白尿、胱抑素 C 和β2 微球蛋白。进行两样本 MR 研究以评估睡眠障碍与肾功能之间的因果关系，并使用多变量 MR 来识别潜在的介导因素。反方差加权法被用作主要估计值。
MR 分析发现了强有力的证据表明，失眠和睡眠时间短与血清肌酐升高的风险增加有关，而不论是否调整肥胖因素。还确定了睡眠时间与 eGFRcys 或胱抑素 C 之间的因果关系。虽然遗传预测的失眠和睡眠时间可能会影响 ARF、CRF、微量白蛋白尿和β2 微球蛋白，但多变量 MR 分析中的 -值变得无统计学意义。未检测到 pleiotropy。
本研究表明失眠对血清肌酐升高的风险有因果影响，睡眠时间对血清肌酐、eGFRcys 和胱抑素 C 有积极影响。我们的研究结果还表明，它们通过肥胖对 ARF、CRF、微量白蛋白尿和β2 微球蛋白的潜在间接影响。
