Guasch A, Myers B D
Stanford University School of Medicine, Division of Nephrology, CA 94305.
J Am Soc Nephrol. 1994 Feb;4(8):1571-81. doi: 10.1681/ASN.V481571.
Physiologic and morphologic techniques were used to elucidate the determinants of the GFR in 25 nephrotic patients with minimal change nephropathy. They were divided into two groups according to the finding of either a normal (Group 1, N = 13) or a depressed (Group 2, N = 12) inulin clearance. RPF, afferent oncotic pressure, and dextran sieving coefficients were determined. Mathematical models of glomerular ultrafiltration were then used to compute likely upper bounds for the ultrafiltration coefficient and pore area/length ratio (a measure of pore density). The upper bounds for each measure of intrinsic ultrafiltration capacity were depressed below estimated normal values in healthy controls by 55 and 47% in Group 1 patients and by 86 and 83% in Group 2 patients with minimal change nephropathy. A corresponding excess of ultrafiltration pressure (versus control), attributable solely to reduced intracapillary oncotic pressure, was by 10.8 and 11.5 mm Hg, respectively. Glomerular morphometry revealed peripheral capillary filtration surface area to be preserved in both minimal change nephropathy groups. However, a significant reduction in filtration slit frequency due to epithelial podocyte broadening correlated with the computed ultrafiltration coefficient across the two minimal change nephropathy groups (r = 0.65; P < 0.001). It was concluded that podocyte deformation invariably lowers the ultrafiltration coefficient and pore area/length ratio in minimal change nephropathy but that an offsetting reduction in intracapillary oncotic pressure prevents the GFR from declining in many cases. However, the models presented here predict that the depression of capillary oncotic pressure is insufficient to compensate when the ultrafiltration coefficient is lowered by substantially more than half and that it is in this circumstance that minimal change nephropathy is most likely to be accompanied by glomerular hypofiltration.
采用生理学和形态学技术，阐明25例微小病变型肾病综合征患者肾小球滤过率（GFR）的决定因素。根据菊粉清除率正常（第1组，N = 13）或降低（第2组，N = 12），将患者分为两组。测定肾血浆流量（RPF）、入球小动脉胶体渗透压和葡聚糖筛过系数。然后使用肾小球超滤数学模型计算超滤系数和孔面积/长度比（孔隙密度的一种度量）的可能上限。在微小病变型肾病第1组患者中，每种内在超滤能力指标的上限比健康对照估计正常值低55%和47%，在第2组患者中则低86%和83%。仅由于毛细血管内胶体渗透压降低导致的超滤压力相应增加（相对于对照），分别为10.8和11.5 mmHg。肾小球形态计量学显示，在两个微小病变型肾病组中，外周毛细血管滤过表面积均得以保留。然而，由于上皮足细胞增宽导致的滤过裂隙频率显著降低，与两个微小病变型肾病组计算出的超滤系数相关（r = 0.65；P < 0.001）。得出的结论是，在微小病变型肾病中，足细胞变形总是会降低超滤系数和孔面积/长度比，但毛细血管内胶体渗透压的相应降低在许多情况下可防止GFR下降。然而，本文提出的模型预测，当超滤系数降低超过一半以上时，毛细血管胶体渗透压的降低不足以进行补偿，正是在这种情况下，微小病变型肾病最有可能伴有肾小球滤过功能减退。
