Ellis D, Lloyd C, Becker D J, Forrest K Y, Orchard T J
Division of Nephrology and Endocrinology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15213, USA.
Am J Kidney Dis. 1996 Jun;27(6):809-18. doi: 10.1016/s0272-6386(96)90518-1.
Diabetic nephropathy (DN) as manifested by persistent and clinically evident proteinuria, has long been considered an irreversible process that predicts a rapid decline in renal function. The observation of reversal of DN in several individuals enrolled in a prospective study of the natural course of diabetes complications challenged this view and led to the current investigation into the correlates of such regression of proteinuria. DN was defined as a median albumin excretion rate (AER) over 200 microg/min in two or three urine collections obtained at baseline, and again at 2 and 4 years of follow-up. Among 658 individuals with childhood-onset insulin-dependent diabetes mellitus (IDDM), 146 had DN at baseline. Nine subsequently died without renal failure, and 13 were lost to follow-up. Of the 124 subjects with at least survey follow-up data, 32 (24%) developed renal failure, and 78 of the remaining 92 provided full quantitative data. AER decreased by > or = 10-fold into the microalbuminuric (20 to 200 microg/min) or normal range (<20 microg/min) in 7 of these individuals and are called "regressors of proteinuria." Compared with the remaining 71 subjects, the strongest correlate of regression of proteinuria was an improvement in fasting plasma low-density lipoprotein cholesterol (LDL-C) in the 7 regressors (P < 0.008). Improved glycemic control was not a significant predictor of improved AER. Five of the 7 individuals with improved AER had a baseline median AER below 500 microg/min. When the 7 regressors of proteinuria were combined with an additional 38 individuals who also experienced smaller decreases in median AER, such improvement was associated with a more favorable systolic (or diastolic) blood pressure (BP) change (P < 0.01), and a decrease in plasma LDL-C level (P = 0.01). These data suggest that proteinuria in DN may substantially regress in approximately 6% and improve in at least 34% of individuals with IDDM over a 4-year period, often in association with a decrease in plasma LDL-C concentration or stabilization or improvement in BP. Furthermore, the data suggest that the nonreversibility threshold for diabetic nephropathy may be higher (500 mg/min) than previously reported (200 microg/min).
糖尿病肾病（DN）表现为持续性且临床上明显的蛋白尿，长期以来一直被认为是一个不可逆的过程，预示着肾功能的快速下降。在一项糖尿病并发症自然病程的前瞻性研究中，观察到数例DN患者病情逆转，这一现象挑战了上述观点，并引发了当前对蛋白尿消退相关因素的研究。DN的定义为：在基线时以及随访2年和4年时，两次或三次尿液收集测得的白蛋白排泄率（AER）中位数超过200微克/分钟。在658例儿童期发病的胰岛素依赖型糖尿病（IDDM）患者中，146例在基线时患有DN。其中9例随后未发生肾衰竭死亡，13例失访。在124例至少有随访调查数据的受试者中，32例（24%）发生肾衰竭，其余92例中的78例提供了完整的定量数据。其中7例患者的AER下降至微蛋白尿范围（20至200微克/分钟）或正常范围（<20微克/分钟），下降幅度≥10倍，这些患者被称为“蛋白尿消退者”。与其余71例受试者相比，7例蛋白尿消退者中，蛋白尿消退的最强相关因素是空腹血浆低密度脂蛋白胆固醇（LDL-C）水平改善（P<0.008）。血糖控制改善并非AER改善的显著预测因素。7例AER改善的患者中，有5例基线AER中位数低于500微克/分钟。当将7例蛋白尿消退者与另外38例AER中位数下降幅度较小的患者合并分析时，这种改善与更有利的收缩压（或舒张压）变化相关（P<0.01），且血浆LDL-C水平下降（P=0.01）。这些数据表明，在4年时间里，DN患者中的蛋白尿在约6%的患者中可能会大幅消退，至少34%的IDDM患者蛋白尿会有所改善，这通常与血浆LDL-C浓度降低或血压稳定或改善有关。此外，数据表明糖尿病肾病的不可逆阈值可能高于先前报道的水平（500毫克/分钟，而非200微克/分钟）。
