可溶性尿激酶受体与慢性肾脏病
Soluble Urokinase Receptor and Chronic Kidney Disease.
作者信息
Hayek Salim S, Sever Sanja, Ko Yi-An, Trachtman Howard, Awad Mosaab, Wadhwani Shikha, Altintas Mehmet M, Wei Changli, Hotton Anna L, French Audrey L, Sperling Laurence S, Lerakis Stamatios, Quyyumi Arshed A, Reiser Jochen
机构信息
From the Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine (S.S.H., Y.-A.K., M.A., L.S.S., S.L., A.A.Q.), and the Department of Biostatistics and Bioinformatics, Emory University (Y.-A.K.) - both in Atlanta; the Department of Medicine, Harvard Medical School, Boston, and Division of Nephrology, Massachusetts General Hospital, Charlestown - both in Massachusetts (S.S.); the Department of Pediatrics, NYU Langone Medical Center, New York (H.T.); and the Department of Medicine, Rush University Medical Center (S.W., M.M.A., C.W., A.L.F., J.R.), and the Women's Interagency HIV Study/CORE Center of Cook County (A.L.H., A.L.F.) - both in Chicago.
出版信息
N Engl J Med. 2015 Nov 12;373(20):1916-25. doi: 10.1056/NEJMoa1506362. Epub 2015 Nov 5.
BACKGROUND
Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease.
METHODS
We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m(2) of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables.
RESULTS
A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was -0.9 ml per minute per 1.73 m(2) among participants in the lowest quartile of suPAR levels as compared with -4.2 ml per minute per 1.73 m(2) among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥ 90 ml per minute per 1.73 m(2)) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m(2), the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile.
CONCLUSIONS
An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation and others.).
背景
可溶性尿激酶型纤溶酶原激活物受体（suPAR）的血浆水平相对较高与局灶节段性肾小球硬化以及多种疾病患者的不良临床结局相关。尚不清楚肾功能正常患者的suPAR水平升高是否与未来估算肾小球滤过率（eGFR）下降及慢性肾脏病的发生有关。
方法
我们测量了埃默里心血管生物样本库中3683名受试者的血浆suPAR水平（平均年龄63岁；65%为男性；suPAR水平中位数为每毫升3040皮克），并确定了2292名受试者入组时及后续随访时的肾功能。在校正人口统计学和临床变量后，使用线性混合模型和Cox回归分析suPAR水平与基线时的eGFR、eGFR随时间的变化以及慢性肾脏病（eGFR<60毫升/分钟/1.73平方米体表面积）发生之间的关系。
结果
基线时较高的suPAR水平与随访期间eGFR的更大下降相关；suPAR水平处于最低四分位数的参与者中，eGFR的年变化为每分钟-0.9毫升/1.73平方米，而处于最高四分位数的参与者中为每分钟-4.2毫升/1.73平方米（P<0.001）。基线时eGFR正常（≥90毫升/分钟/1.73平方米）的921名参与者中，suPAR相关的eGFR下降最大。在1335名基线eGFR至少为60毫升/分钟/1.73平方米的参与者中，suPAR水平处于最高四分位数的参与者进展为慢性肾脏病的风险是最低四分位数参与者的3.13倍（95%置信区间为2.11至4.65）。
结论
在所研究的人群中，suPAR水平升高与慢性肾脏病的发生及eGFR加速下降独立相关。（由亚伯拉罕·J.和菲利斯·卡茨基金会等资助。）
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