Nephrinuria in diabetic nephropathy of type 1 diabetes
Nephrinuria in diabetic nephropathy of type 1 diabetes
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DOI：
10.2337/diabetes.52.12.2969
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发表时间：
2003-12-01
期刊：
影响因子：
7.7
通讯作者：
Holthöfer, H
中科院分区：
文献类型：
--
作者：
Pätäri, A;Forsblom, C;Holthöfer, H
糖尿病肾病是导致终末期肾病的主要原因。由于早期诊断和治疗可以预防并发症，因此需要早期检测的新工具。肾小球滤过狭缝的关键成分之一是nephrin。其表达在糖尿病实验模型中以及在各种人类蛋白尿疾病（包括糖尿病）中改变。我们研究了1型糖尿病合并或不合并肾病患者是否在尿中表现出免疫反应性nephrin，反映了滤过屏障的早期损伤。正常白蛋白尿（n = 40）、微量白蛋白尿（n = 41）和大量白蛋白尿（n = 39）的糖尿病患者和先前正常白蛋白尿但现在检测为微量白蛋白尿阳性的患者（newMcro，n = 39）使用两种亲和纯化的抗肾蛋白抗体，用蛋白质印迹法筛选肾蛋白尿。还研究了非糖尿病健康受试者（n = 29）。30%的正常白蛋白尿患者、17%的微量白蛋白尿患者、28%的大量白蛋白尿患者和28%的新微量白蛋白尿患者出现肾蛋白尿。在女性患者中，35%为肾蛋白尿，而男性患者仅为19%（P = 0.02）。对照组无一例肾尿。结论：1/3的糖尿病患者肾小球滤过屏障受损，表现为早期肾蛋白尿。肾蛋白尿可能具有预后价值，并成为糖尿病肾脏并发症易感性的标志。
Diabetic nephropathy is the leading cause of end-stage renal disease. Because early diagnosis and treatment may prevent the complication, new tools for an early detection are needed. One of the key components of the glomerular filtration slit spanning between neighboring podocytes is nephrin. Its expression is altered in experimental models of diabetes and also in various human proteinuric diseases, including diabetes. We studied whether type 1 diabetic patients with or without nephropathy exhibit immunoreactive nephrin in the urine, reflecting early damage of the filtration barrier. Diabetic patients with normoalbuminuria (n = 40), with microalbuminuria, (n = 41), and with macroalbuminuria (n = 39) and patients previously normoalbuminuric but now testing positive for microalbuminuria (newMcro, n = 39) were screened for nephrinuria with Western blotting using two affinity-purified anti-nephrin antibodies. Nondiabetic healthy subjects (n = 29) were also studied. Nephrinuria was present in 30% of normoalbuminuric, 17% of microalbuminuric, 28% of macroalbuminuric, and 28% of newMicro patients. Of female patients, 35% were nephrinuric compared with only 19% of male patients (P = 0.02). None of the control subjects was nephrinuric. In conclusion, glomerular filtration barrier may be affected in one-third of diabetic patients manifesting as early nephrinuria. Nephrinuria may have prognostic value and become a marker of susceptibility for kidney complications in diabetes.