Nosadini Romano, Tonolo Giancarlo
Endocrinology and Metabolic Diseases, University of Sassari, Sassari, Italy.
J Nephrol. 2003 Nov-Dec;16 Suppl 7:S42-7.
One of the central functions of the kidney is to excrete low molecular weight, water soluble, plasma, waste products into the urine, whereas macromolecules, the size of albumin and larger, are retained. The flow of the glomerular filtrate is thought to follow an extracellular route, passing through the endothelial fenestrae, then across the glomerular basement membrane and finally through the slit diaphragm between the foot processes of podocytes. Recently it has been hypothesized that microalbuminuria leading to proteinuria and to end stage renal disease (ESRD) is mainly due to an altered glomerular fitration barrier at podocyte level. The "conditio sine qua non" for the development of diabetic ESRD is hyperglycemia. However, arterial hypertension and abnormalities of blood lipid concentrations and structure are also an important antecedent of such complication in diabetes mellitus. Interestingly it has been suggested that hyperglycemia, arterial hypertension and dyslipidemia cause disorderes of albumin excretion rate by damaging podocyte and slit diaphragm protein scaffold with over production of and extracellular release of oxygen radical species at glomerular level. The present review will briefly discuss recent reports which describe the relationship between blood glucose and lipid abnormalities and the occurrence and progression of renal damage in diabetes mellitus. More particularly we will give evidence that the risk of a rapid decline of glomerular function abruptly increases when glycated hemoglobin is steadily higher than 7.5% and postprandial blood glucose is above 200 mg/dL. Eventually we will analyze recent reports showing that treatment with statins, the inhibitors of hydroxymethylglutaryl-coenzyme A reductase, ameliorate the course of renal function in type 2 diabetic patients. It is not yet fully understood whether this effect is due to the lowering of the circulating levels of low density lipoproteins (LDL) or to an improved endothelial function or to lower patterns of LDL oxidation.
肾脏的核心功能之一是将低分子量、水溶性的血浆废物排泄到尿液中，而白蛋白及更大尺寸的大分子则被保留。肾小球滤过液的流动被认为遵循细胞外途径，穿过内皮窗孔，然后穿过肾小球基底膜，最后通过足细胞足突之间的裂孔隔膜。最近有人提出，导致蛋白尿和终末期肾病（ESRD）的微量白蛋白尿主要是由于足细胞水平上肾小球滤过屏障的改变。糖尿病性ESRD发生的“必要条件”是高血糖。然而，动脉高血压以及血脂浓度和结构异常也是糖尿病这种并发症的重要先兆。有趣的是，有人提出高血糖、动脉高血压和血脂异常通过在肾小球水平过度产生和细胞外释放氧自由基，破坏足细胞和裂孔隔膜蛋白支架，从而导致白蛋白排泄率紊乱。本综述将简要讨论最近的报告，这些报告描述了血糖和血脂异常与糖尿病肾损伤的发生和进展之间的关系。更具体地说，我们将提供证据表明，当糖化血红蛋白持续高于7.5%且餐后血糖高于200mg/dL时，肾小球功能迅速下降的风险会突然增加。最终，我们将分析最近的报告，这些报告表明，用他汀类药物（羟甲基戊二酰辅酶A还原酶抑制剂）治疗可改善2型糖尿病患者的肾功能进程。目前尚不完全清楚这种作用是由于降低了循环中的低密度脂蛋白（LDL）水平，还是由于改善了内皮功能，抑或是由于降低了LDL氧化模式。
