Krolewski Andrzej S, Skupien Jan, Rossing Peter, Warram James H
Research Division of Joslin Diabetes Center, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Department of Metabolic Diseases, Jagellonian University Medical College, Krakow, Poland.
Kidney Int. 2017 Jun;91(6):1300-1311. doi: 10.1016/j.kint.2016.10.046. Epub 2017 Mar 31.
A new model of diabetic nephropathy in type 1 diabetes 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, progressing steadily (linearly) to end-stage renal disease (ESRD). While an individual's rate of renal decline is constant, the estimated glomerular filtration rate (eGFR) slope varies widely among individuals from -72 to -3.0 ml/min/year. Kidney Disease: Improving Global Outcomes guidelines define rapid progression as rate of eGFR declines > 5 ml/min/year, a value exceeded by 80% of patients in Joslin's type 1 diabetes 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 to 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. Identifying such patients will be the foundation for developing effective individualized methods to prevent or delay onset of ESRD in diabetes.
我们对乔斯林诊所患者的研究得出了1型糖尿病糖尿病肾病的一种新模型。其主要特征是肾功能进行性下降，而非蛋白尿。这种下降是一个单向过程，始于患者肾功能正常时，且在大多数情况下会稳步（呈线性）发展至终末期肾病（ESRD）。虽然个体的肾功能下降速率是恒定的，但估计肾小球滤过率（eGFR）斜率在个体间差异很大，从-72至-3.0毫升/分钟/年不等。改善全球肾脏病预后组织（KDIGO）指南将快速进展定义为eGFR下降速率>5毫升/分钟/年，乔斯林诊所1型糖尿病ESRD队列中80%的患者超过了这一数值。快速进展类别中斜率范围极大，促使我们将其分为“极快速”“快速”和“中度”下降。我们首次表明，在2至10年内从正常eGFR快速下降至ESRD的情况在乔斯林队列中占50%。在本综述中，我们展示了两种糖尿病类型中快速下降者的频率数据，探讨了快速肾功能下降的一些潜在机制，讨论了识别高危患者的方法，并评论了有效治疗干预措施的必要性。快速肾功能下降的起始机制是影响肾小球、肾小管、间质还是血管尚不清楚。由于没有动物模型能模拟肾功能进行性下降，因此需要开展人体研究。寻找预测肾功能下降速率的标志物的前瞻性研究得出的结果可能使检测快速下降者变得可行。识别此类患者将是开发有效个体化方法以预防或延缓糖尿病患者ESRD发病的基础。
