Lemley Kevin V, Blouch Kristina, Abdullah Isha, Boothroyd Derek B, Bennett Peter H, Myers Bryan D, Nelson Robert G
Division of Pediatric Nephrology, Stanford University School of Medicine, Stanford, California.
Division of Nephrology, Stanford University School of Medicine, Stanford, California.
J Am Soc Nephrol. 2000 Nov;11(11):2095-2105. doi: 10.1681/ASN.V11112095.
The development of microalbuminuria in individuals with type 2 diabetes mellitus is associated with a 10-fold increase in the risk of progression to overt nephropathy and eventual end-stage renal failure. The present study reports long-term (up to 8 yr) follow-up of 43 Pima Indians with type 2 diabetes detected on screening to have microalbuminuria. The natural history of albuminuria in these individuals included progression to overt proteinuria (urinary albumin excretion > or = 300 mg/d) in half of the participants by 7 yr of follow-up. The size selectivity of the glomerular barrier was also investigated using dextran sieving and pore theory. Whereas a comparison group of macroalbuminuric Pima Indians had an excess of large pores that served as a macromolecular "shunt," individuals with microalbuminuria had a shunt size no different from long-term diabetic, normoalbuminuric control subjects. An abrupt transition from little or no relationship to a highly significant and positive relationship between increasing albuminuria and shunt size occurred at an albumin-to-creatinine ratio of approximately 3000 mg/g. Shunt size in macroalbuminuric individuals correlated with the extent of foot process broadening. Podocyte foot processes in microalbuminuric participants were not different from those in control subjects. In conclusion, although microalbuminuria in type 2 diabetic Pima Indians often heralds progressive glomerular injury, it is not the result of defects in the size permselectivity of the glomerular barrier but rather of changes in either glomerular charge selectivity or tubular handling of filtered proteins or of a combination of these two factors.
2型糖尿病患者微量白蛋白尿的出现与进展为显性肾病及最终发展至终末期肾衰竭的风险增加10倍相关。本研究报告了43名在筛查时被检测出患有微量白蛋白尿的皮马印第安2型糖尿病患者的长期（长达8年）随访情况。这些个体白蛋白尿的自然病程包括在随访7年时，一半参与者进展为显性蛋白尿（尿白蛋白排泄量≥300mg/d）。还使用葡聚糖筛分和孔隙理论研究了肾小球屏障的大小选择性。大量白蛋白尿的皮马印第安人对照组有过多的大孔隙作为大分子“分流”，而微量白蛋白尿患者的分流大小与长期糖尿病正常白蛋白尿对照受试者无差异。在白蛋白与肌酐比值约为3000mg/g时，白蛋白尿增加与分流大小之间突然从几乎无关联转变为高度显著的正相关。大量白蛋白尿个体的分流大小与足突增宽程度相关。微量白蛋白尿参与者的足细胞足突与对照受试者无差异。总之，虽然2型糖尿病皮马印第安人微量白蛋白尿常预示着进行性肾小球损伤，但它不是肾小球屏障大小选择性缺陷的结果，而是肾小球电荷选择性或滤过蛋白的肾小管处理发生变化或这两个因素共同作用的结果。
