Department of Nephrology, Hospital Rechts der Isar, Technical University of Munich, Munich, Germany.
Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Clin J Am Soc Nephrol. 2020 May 7;15(5):616-624. doi: 10.2215/CJN.11780919. Epub 2020 Apr 14.
Uromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, nonfatal myocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demographics, eGFR, albuminuria, cardiovascular risk factors, and medication.
The mean age of participants was 60±12 years, 60% were male. Mean serum uromodulin concentration was 98±60 ng/ml, eGFR was 49±18 ml/min per 1.73 m, and 78% had eGFR <60 ml/min per 1.73 m. Participants in lower serum uromodulin quartiles had lower eGFR and higher albuminuria, prevalence of diabetes, hypertension, coronary artery disease, and more frequent history of stroke at baseline. During a follow-up of 4 years, 335 participants died, 417 developed MACE, and 229 developed kidney failure. In multivariable analysis, the highest serum uromodulin quartile was associated with lower hazard for mortality (hazard ratio [HR], 0.57; 95% CI, 0.38 to 0.87), MACE (HR, 0.63; 95% CI, 0.45 to 0.90), and kidney failure (HR, 0.24; 95% CI, 0.10 to 0.55) compared with the lowest quartile.
Higher serum uromodulin is independently associated with lower risk for mortality, cardiovascular events, and kidney failure in white patients with CKD.
Deutsches Register für Klinische Studien (DRKS; German national database of clinical studies), DRKS00003971.
尿调蛋白仅由肾小管上皮细胞产生，并释放到尿液和血清中。在中国慢性肾脏病（CKD）患者中，较高的血清尿调蛋白与肾衰竭风险降低相关，在老年人和接受冠状动脉造影的患者中，与死亡率降低相关。我们假设在白人 CKD 患者中，较低的血清尿调蛋白与死亡率、心血管事件和肾衰竭有关。
设计、设置、参与者和测量：我们在德国 CKD（GCKD）研究中招募的 5143 名参与者中测量了血清尿调蛋白。使用多变量 Cox 比例风险回归分析，在队列研究设计中评估基线时血清尿调蛋白与全因死亡率、主要不良心血管事件（MACE；心血管死亡率、非致命性心肌梗死或中风或新发外周血管疾病的复合事件）和肾衰竭（透析或移植）的相关性，调整了人口统计学、肾小球滤过率（eGFR）、白蛋白尿、心血管危险因素和药物因素。
参与者的平均年龄为 60±12 岁，60%为男性。平均血清尿调蛋白浓度为 98±60ng/ml，eGFR 为 49±18ml/min/1.73m，78%的患者 eGFR<60ml/min/1.73m。血清尿调蛋白浓度较低的四分位组的 eGFR 较低，白蛋白尿较多，糖尿病、高血压、冠心病的患病率较高，且基线时中风史更频繁。在 4 年的随访期间，有 335 名参与者死亡，417 名发生 MACE，229 名发生肾衰竭。在多变量分析中，最高四分位组的死亡率（风险比[HR]，0.57；95%置信区间[CI]，0.38 至 0.87）、MACE（HR，0.63；95%CI，0.45 至 0.90）和肾衰竭（HR，0.24；95%CI，0.10 至 0.55）的风险均低于最低四分位组。
在白人 CKD 患者中，较高的血清尿调蛋白与死亡率、心血管事件和肾衰竭风险降低独立相关。
德国临床试验注册处（DRKS；德国国家临床研究数据库），DRKS00003971。
