Deckert T, Feldt-Rasmussen B, Djurup R, Deckert M
Steno Memorial Hospital, Gentofte, Denmark.
Kidney Int. 1988 Jan;33(1):100-6. doi: 10.1038/ki.1988.16.
The pathogenesis of clinical nephropathy in Type 1 (insulin-dependent) diabetes was investigated by measuring renal fractional clearances of albumin, total IgG, IgG4 and beta 2-microglobulin, four plasma proteins which differ in size and charge. Seventy patients and eleven control subjects were studied. In diabetic patients with normal urinary albumin excretion (less than 30 mg/24 hr), fractional IgG clearance was two to three times higher than in control subjects, whereas fractional clearance of the anionic plasma proteins IgG4 and albumin was similar to that of control subjects. These alterations indicate an increase in anionic pore charge within the glomerular basement membrane concomitant with an increase in either pore size or impairment of tubular reabsorption. Diabetic patients, whose urinary albumin excretion has started to rise (30 to 100 mg/24 hr), had unchanged fractional IgG compared to patients with normal albumin excretion, while fractional IgG4 and albumin clearances were increased three- to fourfold; indicating unchanged glomerular pore size, but a decrease in anionic pore charge. In patients demonstrating urinary albumin excretion of greater than 100 mg/24 hr fractional IgG clearance increased to the same extent as fractional albumin clearance, indicating an increase in large pore area. Fractional beta 2-microglobulin clearances were similar to that of control subjects in the different patient groups indicating unchanged tubular reabsorption of proteins. Thus, the increase in large pore area seen in patients with clinical nephropathy is preceded by loss of anionic charge in the glomerular basement membrane. It is likely that this loss of anionic charge is due to loss of heparan sulphate-proteoglycan.
通过测量白蛋白、总IgG、IgG4和β2-微球蛋白这四种大小和电荷不同的血浆蛋白的肾脏分数清除率，对1型（胰岛素依赖型）糖尿病临床肾病的发病机制进行了研究。研究了70例患者和11例对照者。在尿白蛋白排泄正常（低于30mg/24小时）的糖尿病患者中，IgG分数清除率比对照者高两到三倍，而阴离子血浆蛋白IgG4和白蛋白的分数清除率与对照者相似。这些改变表明肾小球基底膜内阴离子孔电荷增加，同时孔径增大或肾小管重吸收受损。尿白蛋白排泄开始升高（30至100mg/24小时）的糖尿病患者，与白蛋白排泄正常的患者相比，IgG分数清除率没有变化，而IgG4和白蛋白分数清除率增加了三到四倍；表明肾小球孔径没有变化，但阴离子孔电荷减少。在尿白蛋白排泄大于100mg/24小时的患者中，IgG分数清除率与白蛋白分数清除率增加到相同程度，表明大孔面积增加。不同患者组中β2-微球蛋白分数清除率与对照者相似，表明肾小管对蛋白质的重吸收没有变化。因此，临床肾病患者中出现的大孔面积增加之前，肾小球基底膜会出现阴离子电荷丢失。这种阴离子电荷丢失可能是由于硫酸乙酰肝素蛋白聚糖的丢失。
