The renal tubulointerstitium in diabetes mellitus.
The renal tubulointerstitium in diabetes mellitus.
复制标题
糖尿病中的肾小管间质。
DOI：
10.1038/ki.1991.57
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发表时间：
1991
影响因子：
19.6
通讯作者：
Goldfarb,S
中科院分区：
文献类型：
--
作者：
Ziyadeh,FN;Goldfarb,S
糖尿病肾损伤是一个重要的临床和生物学问题。大约30%的I型或胰岛素依赖型糖尿病[1]患者和5% - 10%的II型或非胰岛素依赖型糖尿病[2]患者会发展为慢性肾功能不全，需要在终末期肾脏疾病项目中进行治疗。这种损伤的机制、潜在原因和进行性肾功能不全的性质尚不清楚。一般来说，糖尿病主要是一种肾小球疾病，因为在5至12年的时间里，尿白蛋白排泄从15至30µg/min逐渐增加，直到肾病范围的蛋白尿，接着是高血压和肾小球滤过率（GFR）下降，在糖尿病患者的平均持续时间为17年之后。弥漫性肾小球硬化或结节性毛细血管间肾小球硬化的病理病变在晚期糖尿病肾病患者的活检中很常见[3,4]。此外，Mauer及其同事[5]和Osterby and Gunderson[6]表明，肾小球系膜的扩张与患者滤过表面积的下降以及GFR的下降密切相关。这些结果支持糖尿病肾病作为原发性肾小球和可能原发性系膜疾病的观点。然而，一些相互矛盾的观察结果表明，位于肾间质内的非肾小球结构的改变在糖尿病患者肾功能不全的发展中具有潜在的重要作用。下面的讨论将回顾肾小管间质结构和功能改变在糖尿病中作用的证据，并提出小管运输和代谢活动改变导致糖尿病中蛋白尿和肾脏血流动力学改变的假设，以及间质纤维化在糖尿病肾病肾功能不全的最终表达中起重要作用。我们将讨论这些功能和结构变化的几种潜在机制，并提出高血糖在诱导这些异常中的中心发病作用。
Renal injury in diabetes mellitus is an important clinical as well as biological problem. Approximately 30% of patients with type I or insulin-dependent diabetes mellitus [1] and 5 to 10% of patients with type II or non-insulin-dependent diabetes mellitus [2] will develop chronic renal insufficiency requiring treatment in an end-stage renal disease program. The mechanism of this injury, the underlying cause, and the nature of progressive renal insufficiency are unclear. In general, it has been proposed that diabetes is predominantly a glomerular disease as there is a progressive increase in urinary albumin excretion from 15 to 30 µg/min up to nephrotic range proteinuria over 5 to 12 years, followed by hypertension and decline in glomerular filtration rate (GFR) after a mean duration of 17 years of diabetes in the segment of patients at risk. The pathologic lesion of diffuse glomerular sclerosis or nodular intercapillary glomerular sclerosis is typically seen in biopsies from patients with advanced diabetic nephropathy [3, 4]. Moreover, Mauer and colleagues [5] and Osterby and Gunderson [6] have shown that there is a close correlation between the expansion of the glomerular mesangium and the declining filtration surface area, as well as the declining GFR in affected patients. These results support the view of diabetic nephropathy as a primary glomerular and perhaps primary mesangial disorder.However, a number of contradictory observations suggest a potentially important role for alterations in non-glomerular structures which reside within the renal interstitium in the development of renal insufficiency in patients with diabetes mellitus. The following discussion will review the evidence for a role of altered structure and function of the renal tubulointerstitium in diabetes, and propose the hypotheses that altered tubular transport and metabolic activity contributes to proteinuria and altered renal hemodynamics in diabetes, and that interstitial fibrosis plays an important role in the ultimate expression of renal insufficiency in diabetic nephropathy. We will discuss several potential mechanisms for these functional and structural changes and suggest a central pathogenetic role for hyperglycemiaper sein the induction of these abnormalities.