Liu Xiaoning, Liu Mengna, Zhong Bijuan, He Xinxin, Xu Yalai, Zhou Zheng, Qin Pei
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450014, People's Republic of China.
School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.
Nat Sci Sleep. 2025 Jun 7;17:1205-1215. doi: 10.2147/NSS.S503387. eCollection 2025.
It remains unclear about the causal association between obstructive sleep apnea (OSA) and chronic kidney disease (CKD) and renal function. This study aimed to explore the bidirectional causal relationship between OSA and CKD and renal function.
We used a 2-sample bidirectional Mendelian randomization (MR) method to evaluate the causal relationship between OSA and estimated glomerular filtration rate from creatinine (eGFRcrea), eGFR from cystatin C (eGFRcys), urine albumin to creatinine ratio (UACR), blood urea nitrogen (BUN), and chronic kidney disease (CKD). Inverse variance weighted (IVW), MR-Egger, weighted median, MR-Egger, and pleiotropy residual sum and outlier test (MR-PRESSO) were used to calculate the β or odds ratio [OR] and their 95% CIs.
Genetically predicted OSA was found to be associated with BUN (β=0.040, 95% CI: 0.013-0.067, p = 0.003), but not associated with CKD (OR = 1.075, 95% CI: 0.916-1.263, p = 0.375), eGFRcrea (β=0.007, 95% CI: -0.004-0.017, p = 0.203), eGFRcys (β=-0.012, 95% CI: -0.026-0.002, p = 0.102), or UACR (β=-0.025, 95% CI: -0.058-0.007, p = 0.122). In the reverse analysis, genetically predicted eGFRcys (OR, 0.687; 95% CI, 0.497-0.950, p = 0.023) and BUN (OR, 1.686; 95% CI, 1.299-2.073, p = 0.008) was associated with an increased risk of OSA. The Cochrane's Q test reveals significant heterogeneity between various single nucleotide polymorphisms. MR-Egger indicated no evidence of genetic pleiotropy. Results were robust using other MR methods in sensitivity analyses.
Through the two-sample MR analysis, we identified kidney function may have a causal relationship with OSA, but a causal relationship between OSA and CKD and kidney function remains uncertain. More studies are required to better understand the relationship between OSA and CKD and kidney function.
阻塞性睡眠呼吸暂停（OSA）与慢性肾脏病（CKD）及肾功能之间的因果关系仍不明确。本研究旨在探讨OSA与CKD及肾功能之间的双向因果关系。
我们采用两样本双向孟德尔随机化（MR）方法来评估OSA与基于肌酐的估计肾小球滤过率（eGFRcrea）、基于胱抑素C的eGFR（eGFRcys）、尿白蛋白肌酐比值（UACR）、血尿素氮（BUN）以及慢性肾脏病（CKD）之间的因果关系。采用逆方差加权（IVW）、MR-Egger、加权中位数、MR-Egger以及多效性残差总和与离群值检验（MR-PRESSO）来计算β或比值比[OR]及其95%置信区间。
发现基因预测的OSA与BUN相关（β = 0.040，95%置信区间：0.013 - 0.067，p = 0.003），但与CKD（OR = 1.075，95%置信区间：0.916 - 1.263，p = 0.375）、eGFRcrea（β = 0.007，95%置信区间： - 0.004 - 0.017，p = 0.203）、eGFRcys（β = - 0.012，95%置信区间： - 0.026 - 0.002，p = 0.102）或UACR（β = - 0.025，95%置信区间： - 0.058 - 0.007，p = 0.122）无关。在反向分析中，基因预测的eGFRcys（OR，0.687；95%置信区间，0.497 - 0.950，p = 0.023）和BUN（OR，1.686；95%置信区间，1.299 - 2.073，p = 0.008）与OSA风险增加相关。Cochrane's Q检验显示各种单核苷酸多态性之间存在显著异质性。MR-Egger表明没有基因多效性的证据。在敏感性分析中使用其他MR方法时结果稳健。
通过两样本MR分析，我们确定肾功能可能与OSA存在因果关系，但OSA与CKD及肾功能之间的因果关系仍不确定。需要更多研究来更好地理解OSA与CKD及肾功能之间的关系。
