血清尿调蛋白与慢性肾脏病患者肾脏疾病进展的关系。
Serum uromodulin and progression of kidney disease in patients with chronic kidney disease.
机构信息
Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, 100034, China.
The First Affiliated Hospital, Baotou Medical College, Baotou, 014010, China.
出版信息
J Transl Med. 2018 Nov 19;16(1):316. doi: 10.1186/s12967-018-1693-2.
BACKGROUND
Uromodulin is specifically synthesized and secreted by kidney tubular epithelial cells. Studies on the association of serum uromodulin and outcomes of chronic kidney disease (CKD) are lacking. This study aimed to evaluate whether serum uromodulin was associated with outcomes of patients with CKD.
METHODS
We measured serum uromodulin concentrations by ELISA in 2652 CKD patients from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) and investigated the association of serum uromodulin with outcomes of CKD patients, including end-stage kidney disease (ESKD) receiving kidney replacement therapy, cardiovascular events and mortality by Cox proportional hazards regression model.
RESULTS
A total of 2652 CKD patients were enrolled in this study, with an age of 48.7 ± 13.8 years and the baseline eGFR of 49.6 ± 29.4 mL/min/1.73 m, of whom 58.4% were male. The median level of urinary albumin/creatinine ratio and serum uromodulin was 473.7 mg/g (IQR 134.1-1046.6 mg/g) and 77.2 ng/mL (IQR 48.3-125.9 ng/mL), respectively. Altogether, 404 ESKD, 189 cardiovascular events, and 69 deaths occurred during the median follow-up of 53.6 (IQR 44.0-64.0) months. Lower levels of serum uromodulin were independently associated with higher risk of incident ESKD after adjusting for traditional cardiovascular risk factors, with the hazard ratios (HRs) of 3.23 (95% confidence intervals [CIs] 2.15-4.85) for the middle tertile and 7.47 (95% CI 5.06-11.03) for the bottom tertile, compared with top tertile and 0.31 (95% CI 0.25-0.38) per every standard deviation increase. After further adjustment for the baseline eGFR, the association was greatly attenuated, but still significant, with HRs of 1.92 (95% CI 1.26-2.90) for the bottom tertile compared with top tertile and 0.69 (95% CI 0.55-0.86) per every standard deviation increase.
CONCLUSIONS
Serum uromodulin is independently associated with an increased risk of incident ESKD in CKD patients.
背景
尿调蛋白特异性地由肾脏管状上皮细胞合成和分泌。关于血清尿调蛋白与慢性肾脏病（CKD）结局的研究尚缺乏。本研究旨在评估血清尿调蛋白是否与 CKD 患者的结局相关。
方法
我们采用酶联免疫吸附试验（ELISA）检测了来自中国慢性肾脏病队列研究（C-STRIDE）的 2652 例 CKD 患者的血清尿调蛋白浓度，并通过 Cox 比例风险回归模型探讨了血清尿调蛋白与 CKD 患者结局的相关性，结局包括接受肾脏替代治疗的终末期肾病（ESKD）、心血管事件和死亡。
结果
本研究共纳入 2652 例 CKD 患者，年龄为 48.7±13.8 岁，基线估算肾小球滤过率（eGFR）为 49.6±29.4 mL/min/1.73 m，其中 58.4%为男性。尿白蛋白/肌酐比值和血清尿调蛋白的中位数水平分别为 473.7 mg/g（IQR：134.1-1046.6 mg/g）和 77.2 ng/mL（IQR：48.3-125.9 ng/mL）。中位随访 53.6（IQR：44.0-64.0）个月期间，共发生 404 例 ESKD、189 例心血管事件和 69 例死亡。在校正传统心血管危险因素后，较低的血清尿调蛋白水平与 ESKD 发病风险增加独立相关，中三分位组的风险比（HR）为 3.23（95%置信区间[CI]：2.15-4.85），底三分位组为 7.47（95% CI：5.06-11.03），与最高三分位组相比，每增加一个标准差的血清尿调蛋白水平，HR 为 0.31（95% CI：0.25-0.38）。进一步校正基线 eGFR 后，相关性虽减弱，但仍具有统计学意义，底三分位组与最高三分位组相比，HR 为 1.92（95% CI：1.26-2.90），每增加一个标准差的血清尿调蛋白水平，HR 为 0.69（95% CI：0.55-0.86）。
结论
血清尿调蛋白与 CKD 患者发生 ESKD 的风险增加独立相关。
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