Forty-one patients with a
nephrotic syndrome and biopsy-proven
membranous nephropathy were administered a 3 to 6-month course of
cyclosporine (CsA;4 to 5 mg/kg per day). Differential solute clearances were used to evaluate glomerular function, before and after
therapy. CsA lowered median
proteinuria by 56%, from 7.3 to 3.2 g/24 h (P < 0.0001). Corresponding mean increments in
serum albumin,
immunoglobulin G, and oncotic pressure values were 31, 32, and 26%, respectively (all P < 0.0001). Arterial pressure, GFR, and renal plasma flow remained constant, but CsA restored the
dextran-sieving curve toward normal, lowering the computed fraction of shunt-like pores by 25% (P < 0.05). In 14 instances, a cross-over design was used to randomly assign patients to 3 months of CsA versus 3 months of
enalapril (10 to 30 mg daily), separated by a 1-month washout interval. Although
enalapril lowered arterial pressure by 8 mm Hg (P < 0.01), it had no effect on
proteinuria,
plasma protein composition, filtration dynamics, or
dextran sieving (all P = not significant). CsA dependence of
proteinuria, indicated by relapsing
nephrosis after CsA withdrawal, required additional courses of CsA to maintain
proteinuria subnephrotic in most patients. In six patients with declining GFR during prolonged CsA treatment, a repeat biopsy showed more prominent immune deposits and a thicker glomerular basement membrane than at baseline. It was concluded that: (1) CsA lowers
proteinuria in MN in part, by enhancing barrier size-selectivity; (2) lack of comparable efficacy of
enalapril suggests that the antiproteinuric effect of CsA is related to its immuno-suppressive rather than glomerulodepressor properties; but (3) judged by repeat biopsy, CsA does not prevent continuing
autoantibody formation in this disorder.