Avila-Casado Maria del Carmen, Perez-Torres Israel, Auron Ari, Soto Virgilia, Fortoul Teresa I, Herrera-Acosta Jaime
Department of Pathology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico.
Kidney Int. 2004 Jul;66(1):133-43. doi: 10.1111/j.1523-1755.2004.00715.x.
Primary collapsing glomerulopathy recurs postransplant, raising the possibility of circulating factors implicated in the pathogenesis of the disease.
To determine the presence of circulating factors in collapsing glomerulopathy patients, we tested serum from those patients in an in vivo assay. Eleven groups of rats received serum from collapsing glomerulopathy patients, idiopathic focal segmental glomerulosclerosis (FSGS) or healthy subjects in its native form, isolated IgG, or serum without IgG. The presence of proteinuria and creatinine clearance were determined. Histopathologic analysis included light, immunofluorescence, and electron microscopy.
Collapsing glomerulopathy rats developed proteinuria while rats injected with serum from FSGS and healthy subjects did not. Rats injected with serum of collapsing glomerulopathy in its native form developed marked proteinuria (99.2 +/- 42 mg/24 hours at day 5, P= 0.0001, compared to the baseline), and decreased in creatinine clearance. Rats receiving isolated IgG or serum without IgG from collapsing glomerulopathy developed mild proteinuria (46.5 +/- 8.4 mg/24 hours and 30.9 +/- 11 mg/24 hours, respectively, at day 5 (P= 0.0001). Glomerular tuft retraction and podocyte damage were seen only in collapsing glomerulapthy rats. No abnormalities were found in rats injected with serum from FSGS or healthy subjects.
Circulating factors in the serum of collapsing glomerulopathy patients produce podocyte damage, whereas such factors are not present in noncollapsing FSGS. IgG eluates from collapsing glomerulopathy produce proteinuria when injected into the rat. Such factors remain in the circulation when serum of patients is adsorbed into protein A, raising the possibility that there are more than one circulating factor present in patients with collapsing glomerulopathy.
原发性塌陷性肾小球病在移植后会复发，这增加了循环因子参与该疾病发病机制的可能性。
为了确定塌陷性肾小球病患者体内循环因子的存在情况，我们在一项体内试验中检测了这些患者的血清。11组大鼠分别接受了塌陷性肾小球病患者、特发性局灶节段性肾小球硬化（FSGS）患者或健康受试者的天然血清、分离出的IgG，或不含IgG的血清。测定蛋白尿的存在情况和肌酐清除率。组织病理学分析包括光镜、免疫荧光和电镜检查。
塌陷性肾小球病大鼠出现蛋白尿，而注射FSGS患者和健康受试者血清的大鼠未出现蛋白尿。注射塌陷性肾小球病天然血清的大鼠出现明显蛋白尿（第5天时为99.2±42mg/24小时，与基线相比P = 0.0001），肌酐清除率下降。接受塌陷性肾小球病患者分离出的IgG或不含IgG血清的大鼠出现轻度蛋白尿（第5天时分别为46.5±8.4mg/24小时和30.9±11mg/24小时，P = 0.0001）。仅在塌陷性肾小球病大鼠中观察到肾小球毛细血管袢皱缩和足细胞损伤。注射FSGS患者或健康受试者血清的大鼠未发现异常。
塌陷性肾小球病患者血清中的循环因子会导致足细胞损伤，而非塌陷性FSGS患者血清中不存在此类因子。塌陷性肾小球病患者的IgG洗脱液注入大鼠体内时会产生蛋白尿。当患者血清吸附到蛋白A上时，此类因子仍留在循环中，这增加了塌陷性肾小球病患者体内存在多种循环因子的可能性。
