Proteinuria and Fusion of Podocyte Foot Processes in Rats after Infusion of Cytokine from Patients with Idiopathic Minimal Lesion Nephrotic Syndrome

BACKGROUND/AIMS: We report on the isolation of a factor secreted by peripheral blood mononuclear cells from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse and its effect on proteinuria and podocyte morphology in the rat. METHODS: Peripheral blood mononuclear cells from patients with IMLNS (in relapse and in remission) and patients with focal segmental glomerulosclerosis were cultured for 72 h. Supernatants from 20 x 10(6) cultured cells were separated by liquid chromatography into three fractions according to markers (bovine serum albumin, beta-amylase, and apoferritin). Each supernatant fraction was infused into rats for 5 days using an osmotic pump. Proteinuria, 24-hour albumin excretion or albumin/creatinine ratio in a 24-hour urine collection, was measured daily starting 3 days prior to fraction infusion. Renal tissue was obtained for electron microscopy studies. The beta-amylase fraction underwent electrophoresis using isoelectric focusing gel. RESULTS: When protein excretion was compared prior to and during supernatant fraction infusion, a significant increase in proteinuria was observed only when beta-amylase fraction from IMLNS patients in relapse was infused (p < 0.05). Protein electrophoresis of the beta-amylase fraction showed a single band at pH 6.0 only in samples from IMLNS patients in relapse. The band was composed of two proteins, beta-amylase and a 100-kDa glycoprotein. Fusion of foot processes was observed only when the beta-amylase fraction from IMLNS patients in relapse was infused. CONCLUSIONS: The infusion of the beta-amylase fraction containing a 100-kDa glycoprotein from IMLNS patients in relapse induced proteinuria and effacement of foot processes in the rat. This protein may play a role in the pathogenesis of IMLNS.