Long term treatment of IgA nephropathy with cyclosporine A

Abstract

20-50% of patients with IgA nephropathy (IgAN) reach end-stage renal failure. Yet a standard treatment for those with progressive course and/or great proteinuria is lacking. We treated 6 patients with biopsy proven IgAN, proteinuria over 3.5 g/24 h and S-creatinine less than 200 micromol/L non-responding to corticosteroids administered for 3 months. They were given cyclosporine A (CsA) 5 mg/kg bw/day then titrated aiming at a serum concentration of 70-150 ng/mL for one year tapered to discontinuation in 9 months. Prednisone 5-10 mg on alternate days was given with CsA. Proteinuria (g/day) decreased from 4.66 +/- 0.43 to 1.38 +/- 0.29 (p < 0.01) after 1 month and to 0.59 +/- 0.14 (p < 0.001) after 1 year of treatment and remained lower than baseline 2 years from the beginning (1.44 +/- 0.27, p < 0.001). GFR (creatinine clearance) did not change during the first month (1.25 +/- 0.21 mL/s vs 1.38 +/- 0.29 mL/s), but decreased after 1 year (1.05 +/- 0.14 mL/s, p < 0.05). After two years it increased to 1.17 +/- 0.16, NS from baseline. We also calculated the ratio of proteinuria to the GFR (mg/L) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80 + 6.47 before therapy, it decreased after 1 month (11.56 +/- 1.7, p < 0.05) and further after 1 year (6.78 + 1.45, p < 0.01). Three months after discontinuation it was still 14.32 +/- 1.00, p < 0.05 from baseline. In conclusion, CsA significantly lowered moderate to high proteinuria in 6 patients with IgAN. Significant decrease of the proteinuria/GFR ratio suggests some non-hemodynamic mechanism of CsA action. The therapy was well tolerated and side-effects were not so severe as to require CsA withdrawal.