Cyclosporin A reduces albuminuria in experimental anti-GBM nephritis independently from changes in GFR.

Cyclosporin A (CsA) can reduce proteinuria in various forms of human and 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 glomerular basement membrane (GBM). We studied the antiproteinuric effect of CsA in the heterologous phase of a passively induced anti-GBM nephritis in the mouse. This passive model characterized by acute exudative glomerular lesions and a dose-dependent albuminuria. Rabbit anti-mouse GBM antibodies were administered intravenously in C57B110 mice at day 4, after 3 days of pretreatment with either CsA (75 mg/kg body weight) (=15) or olive oil (OO, controls, =15) orally. CsA did not influence the severity of the histological lesions. Albuminuria was substantially reduced by CsA (CsA 1.6±1.8; OO 5.6±3.2 mg/18 h; <0.002). There was considerable concomitant reduction of the GFR by CsA, as measured with a Cr-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; <0.01. This drug-induced decrease of GFR was prevented by simultaneous treatment with phenoxybenzamine (PB) twice daily 45 μg 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; =NS). Although the CsA-induced GFR reduction was prevented, CsA still reduced albuminuria significantly (PB and CsA, 2.2±1.8; controls (PB and OO), 5.6±1.8 mg/18 h; =0.003). Therefore the antiproteinuric effect of CsA in this model seems to result not only from a reduction of the GFR but also from reduction of the permselectivity of the GBM for proteins. [ABSTRACT FROM PUBLISHER]