Extent of glomerular injury in active and resolving lupus nephritis: a theoretical analysis.
Extent of glomerular injury in active and resolving lupus nephritis: a theoretical analysis.
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活动性和缓解性狼疮性肾炎的肾小球损伤程度：理论分析。
DOI：
10.1152/ajprenal.1991.260.5.f717
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Sibley,RK
中科院分区：
文献类型：
--
作者：
Myers,BD;Chagnac,A;Golbetz,H;Newton,L;Strober,S;Sibley,RK
对22例弥漫性增生性狼疮性肾炎（DPLN）患者在免疫抑制治疗前和治疗6-12个月后分别进行了不同溶质清除率（n = 22）和连续肾活检（n = 11）。用异孔膜模型分析了不同粒径葡聚糖的肾小球筛分。这表明活性DPLN与1）总体孔密度降低伴肾小球滤过率（GFR）降低53%，和2）出现大的非歧视性孔子集相关，这是观察到的肾病蛋白尿水平。活检组织的形态学分析提供了由于肾小球簇中毛细血管袢的整体或节段性闭塞导致滤过表面积减少的证据。治疗后DPLN活性消退。计算孔密度的增加与GFR增加24%相关;分流样孔分数的显著减少伴随着蛋白尿平行减少至亚肾病范围。重复活检显示肾小球细胞减少，免疫沉积物减少，并随之增加的部分簇面积所占的专利循环。上皮滤过裂隙频率也增加。然而，功能和结构的恢复都不完全。残余孔隙密度仅为健康对照的23 - 35%，相应的分流样孔隙突出三倍。我们的结论是，严重的DPLN是目前的治疗方式，只有部分可逆的，并随之而来的残余损伤是远远超过传统的肾功能测试所建议的严重。
Patients with diffuse, proliferative lupus nephritis (DPLN) were subjected to differential solute clearances (n = 22) and serial renal biopsy (n = 11) before and again after 6-12 mo of immunosuppressive therapy. Glomerular sieving of dextrans of graded size was analyzed with a heteroporous membrane model. This revealed active DPLN to be associated with 1) a reduction of overall pore density accompanied by a 53% depression of glomerular filtration rate (GFR), and 2) appearance of a subset of large, nondiscriminatory pores, which accounted for the observed nephrotic level of proteinuria. Morphometric analysis of biopsy tissue provided evidence of reduced filtration surface area due to global or segmental occlusion of capillary loops in glomerular tufts. Activity of DPLN resolved posttreatment. A computed increase in pore density was associated with a 24% increment in GFR; a marked reduction in the fraction of shuntlike pores was accompanied by a parallel reduction of proteinuria into a subnephrotic range. Repeat biopsy revealed diminished glomerular cellularity, fewer immune deposits, and an ensuing increase in the fraction of tuft area occupied by patent loops. Epithelial filtration slit frequency also increased. Neither functional nor structural recovery was complete, however. Residual pore density approximated only 23-35% of that in healthy controls, and corresponding shuntlike pores were threefold more prominent. We conclude that severe DPLN is only partially reversible by current modalities of treatment and that the ensuing residual injury is far more severe than suggested by conventional tests of renal function.