Fast renal decline to end-stage renal disease: an unrecognized feature of nephropathy in diabetes.
Fast renal decline to end-stage renal disease: an unrecognized feature of nephropathy in diabetes.
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DOI：
10.1016/j.kint.2016.10.046
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发表时间：
2017-06
影响因子：
19.6
通讯作者：
Warram JH
中科院分区：
文献类型：
--
作者：
Krolewski AS;Skupien J;Rossing P;Warram JH
我们对 Joslin Clinic 患者的研究中出现了一种新的 T1D 糖尿病肾病模型。主要特征是进行性肾功能衰退，而不是蛋白尿。这种下降是一个单向过程，从患者肾功能正常时开始，并且在大多数情况下，稳定（线性）进展至终末期肾病（ESRD）。虽然个体的肾功能衰退率是恒定的，但 eGFR 斜率在个体之间变化很大，从 -72 到 -3.0 毫升/分钟/年。 KDIGO 指南将快速进展定义为 eGFR 下降率 <−5 ml/min/年，Joslin 的 T1D ESRD 队列中 80% 的患者超过了该值。快速进展类别中的坡度范围非常大，促使我们将其分为“非常快”、“快速”和“中等”下降。我们首次表明，Joslin 队列中 50% 的人在 2-10 年内从正常 eGFR 快速下降到 ESRD。在这篇综述中，我们提供了两种糖尿病类型快速下降频率的数据，调查了肾快速下降的一些机制，讨论了识别高危患者的方法，并对有效治疗干预的必要性进行了评论。肾功能快速衰退的起始机制是否影响肾小球、肾小管、间质或脉管系统尚不清楚。由于没有动物模型可以模拟进行性肾功能衰退，因此需要对人类进行研究。前瞻性研究寻找预测肾功能衰退速度的标志物，结果可能使快速肾功能衰退者的检测变得可行。认识到此类患者将成为开发有效的个性化方法来预防或延迟糖尿病 ESRD 发病的基础。
A new model of diabetic nephropathy in T1D emerged from our studies of Joslin Clinic patients. The dominant feature is progressive renal decline, not albuminuria. This decline is a unidirectional process commencing while patients have normal renal function and, in the majority, progresses steadily (linearly) to ESRD. While an individual’s rate of renal decline is constant, the eGFR slope varies widely among individuals from −72 to −3.0 ml/min/year. KDIGO guidelines define rapid progression as rate of eGFR decline <−5 ml/min/year, a value exceeded by 80% of patients in Joslin’s T1D ESRD cohort. The extraordinary range of slopes within the rapid progression category prompted us to partition it into “very fast”, “fast” and “moderate” decline. We showed for the first time that very fast and fast decline from normal eGFR to ESRD within 2–10 years constitutes 50% of the Joslin cohort. In this review we present data about frequency of fast decliners in both diabetes types, survey some mechanisms underlying fast renal decline, discuss methods of identifying patients at risk and comment on the need for effective therapeutic interventions. Whether the initiating mechanism of fast renal decline affects glomerulus, tubule, interstitium or vasculature is unknown. Since no animal model mimics progressive renal decline, studies in humans are needed. Prospective studies searching for markers predictive of the rate of renal decline yield findings that may make detection of fast decliners feasible. Recognizing such patients will be the foundation for developing effective personalized methods to prevent or delay onset of ESRD in diabetes.