Short-Term Responsiveness of Membranous Glomerulopathy to Cyclosporine

We administered a 12-week course of cyclosporine (CsA) (4 to 6 mg/kg/24 h) to nephrotic patients with membranous glomerulopathy (MG). Nephrotic patients with minimal change nephropathy (MCN) served as a comparison group. We evaluated the effects of CsA on proteinuria, glomerular function, and the release of cytokines by peripheral blood mononuclear cells in culture. Proteinuria was restored to normal levels within 2 to 4 weeks in MCN. Proteinuria declined from nephrotic to subnephrotic levels (< 3,500 mg/24 h) in 10 of 14 patients with MG, also within 2 to 4 weeks of onset of therapy. The four nonresponders exhibited a rapidly progressive and presumably irreversible form of MG culminating in renal failure. On average, fractional clearances of albumin and IgG declined by 59% and 73% in MG (P < 0.005); corresponding declines in MCN were by 99% (P < .0001). Corresponding rates of glomerular filtration in each glomerular injury remained unchanged. A strong trend for proteinuria to relapse after CsA was withdrawn was evident in both disorders. The release of tumor necrosis factor (TNF)-alpha by mononuclear cells in culture was enhanced in each glomerular injury, both before and after the course of CsA. We conclude that the proteinuria in most cases of MG exhibits a responsiveness to CsA that is qualitatively similar to, but less complete than, that in MCN. The rapidity with which barrier function improves suggests a possible role for cell-mediated immune injury in MG.