ANTIPROTEINURIC EFFECT OF CYCLOSPORINE-A IN ADRIAMYCIN NEPHROPATHY INRATS

Ciclosporin A (CsA) can reduce proteinuria in various forms of human a nd experimental glomerulopathies. This antiproteinuric effect can be t he result of a decrease of immunological damage, a decrease in the glo merular filtration rate (GFR), or a change in the permselective proper ties of the glomerular capillary wall. In this study we investigated t he effect of CsA on Adriamycin-induced nephropathy in rats. A single i ntravenous injection of Adriamycin (5 mg/kg body weight) induced a sev ere nephrotic syndrome with a massive albuminuria (+/- 400 mg/24 h fro m 3 weeks onwards) and a hypoalbuminemia (+/- 7 mg/ml after 5 weeks). The IgG/albumin selectivity index was 0.16 +/- 0.05, indicating a pref erential loss of albumin. A 5-day treatment with CsA reduced the album in excretion by almost 50% (from 336 +/- 91 to 178 +/- 58 mg/24 h; p = 0.002) and induced an increase in the serum albumin level (from 7.1 /- 4.1 to 12.8 +/- 3.2 mg/ml; p = 0.002) in contrast to the vehicle ol ive oil (OO). CsA also decreased the GFR by 40% (from 0.74 +/- 0.11 to 0.41 +/- 0.11 mg/ml/100 g body weight; p = 0.002). Albuminuria correc ted for the GFR (fractional excretion of albumin, FE(alb)) was still s ignificantly lower in CsA-treated than in OO-treated animals (FE(alb) CsA: 1.35 +/- 0.88, FE(alb) OO: 3.17 +/- 2.29%; p = 0.0005). This sugg ests that other factors are also involved in the reduction of albuminu ria. To exclude that CsA has an effect on the tubular reabsorption of albumin, we evaluated the blockade of the tubular reabsorption by lysi ne and found no difference in albuminuria between the CsA- and GO-trea ted groups. These experiments suggest that the antiproteinuric effect of CsA is not (only) due to a decrease in the GFR, but also to a decre ase of the enhanced permeability of the glomerular capillary wall for albumin.