CYCLOSPORINE-A REDUCES ALBUMINURIA IN EXPERIMENTAL ANTI-GEM NEPHRITISINDEPENDENTLY FROM CHANGES IN GFR

Cyclosporin A (CsA) can reduce proteinuria in various forms of human a nd experimental glomerulonephritis. This antiproteinuric effect of CsA may be the consequence of diminution of immunological damage, a drug- induced decrease of GFR, or changes in permselectivity of the glomerul ar basement membrane (GEM). We studied the antiproteinuric effect of C sA in the heterologous phase of a passively induced anti-GEM nephritis in the mouse. This passive model is characterized by acute exudative glomerular lesions and a dose-dependent albuminuria. Rabbit anti-mouse GEM antibodies were administered intravenously in C57B110 mice at day 4, after 3 days of pretreatment with either CsA (75 mg/kg body weight ) (n=15) or olive oil (OO, controls, n=15) orally. CsA did not influen ce the severity of the histological lesions. Albuminuria was substanti ally reduced by CsA (CsA 1.6+/-1.8; OO 5.6+/-3.2 mg/18 h; P<0.002). Th ere was a considerable concomitant reduction of the GFR by CsA, as mea sured with a Cr-51-EDTA single-shot plasma clearance technique before (day - 1) and during treatment (day 4): GFR ratio day 4/day-1 for CsA, 0.4+/-0.1; for OO controls, 1.1+/-0.6; P<0.01. This drug-induced decr ease of GFR was prevented by simultaneous treatment with phenoxybenzam ine (PB) twice daily 45 mu g orally for 4 days (GFR ratio day 4/day-1 for PB and CsA, 0.9+0.4; controls (PB and OO), 1.0+/-0.4; P=NS). Altho ugh the CsA-induced GFR reduction was prevented, CsA still reduced alb uminuria significantly (PB and CsA, 2.2+/-1.8; controls (PB and OO), 5 .6+/-1.8 mg/18 h; P=0.003). Therefore the antiproteinuric effect of Cs A in this model seems to result not only from a reduction of the GFR b ut also from a reduction of the permselectivity of the GEM for protein s.