Guasch A, Hashimoto H, Sibley R K, Deen W M, Myers B D
Department of Medicine, Stanford University Medical Center, California 94305.
Am J Physiol. 1991 May;260(5 Pt 2):F728-37. doi: 10.1152/ajprenal.1991.260.5.F728.
Fractional clearances (theta) of uncharged dextrans (radii 28-60 A) were used to characterize glomerular dysfunction in 34 nephrotic humans with either minimal-change nephropathy (MCN) or focal, segmental glomerulosclerosis (FSGS). A theoretical analysis of theta of dextran with a heteroporous membrane model revealed a similar alteration, more marked in FSGS than MCN. The number of restrictive pores perforating the major membrane component was reduced in parallel with the prevailing glomerular filtration rate (GFR). Parallel shuntlike pores in the remaining membrane component were more prominent, pointing to impaired size selectivity. However, the theta of large (60 A) dextrans attributable to these shunts exceeded control in FSGS only, suggesting that coexistent impairment of charge selectivity contributed importantly to the proteinuria in MCN. Membrane properties returned toward normal when MCN remitted. Glomerular morphometry revealed the frequency of epithelial filtration slits to vary with the extent of membrane dysfunction. Despite offsetting hypertrophy of remnant glomeruli in FSGS, a loss of filtration surface due to sclerosis likely contributed to the more marked reductions in pore number and GFR observed in this disorder than in MCN.
使用不带电荷的右旋糖酐（半径28 - 60 Å）的分数清除率（θ）来表征34例患有微小病变性肾病（MCN）或局灶节段性肾小球硬化症（FSGS）的肾病患者的肾小球功能障碍。用异孔膜模型对右旋糖酐的θ进行理论分析，结果显示出类似的改变，在FSGS中比在MCN中更明显。贯穿主要膜成分的限制性孔的数量与主要的肾小球滤过率（GFR）平行降低。剩余膜成分中的平行分流样孔更为突出，表明大小选择性受损。然而，仅在FSGS中，归因于这些分流的大（60 Å）右旋糖酐的θ超过了对照，这表明电荷选择性的共存损害对MCN中的蛋白尿有重要影响。当MCN缓解时，膜特性恢复正常。肾小球形态计量学显示上皮滤过裂隙的频率随膜功能障碍的程度而变化。尽管FSGS中残余肾小球有代偿性肥大，但由于硬化导致的滤过面积丧失可能是该疾病中观察到的孔数量和GFR的降低比MCN中更明显的原因。
