Tacrolimus is an alternative therapy option for the treatment of adult steroid-resistant nephrotic syndrome: a prospective, multicenter clinical trial.

Background: The optimal therapy for adult steroid-resistant nephrotic syndrome (SRNS) remains a therapeutic challenge. We investigated the efficacy and safety of tacrolimus as a promising regimen in Chinese adult patients.

Methods: A prospective, multicenter trial was conducted in 9 nephrology centers from 2006 to 2008, in patients with SRNS (defined as failure to respond to 1 mg/kg/day of prednisone for 8, and 16 weeks, in focal segmental glomerulosclerosis). Patients were treated with tacrolimus (TAC) plus prednisone for 12 months. TAC dose was titrated to achieve a target trough blood concentration of 5-10 ng/ml for the first 6 months and 4-6 ng/ml for the subsequent 6 months. The primary outcomes included complete or partial remission [complete remission (CR): proteinuria <0.3 g/24 h, with serum albumin ≥ 3.5 g/dl and stable renal function; partial remission (PR): proteinuria between 0.3 and 3.5 g/24 h and a decrease of at least 50 % from the baseline level, with serum albumin ≥ 3.0 g/dl and stable renal function]. Secondary end-points included relapse rate, changes of clinical parameters (proteinuria, serum albumin, and lipid profile) and adverse events.

Results: Twenty-four patients with SRNS were enrolled. After 6 months of therapy, CR was achieved in 58.3 % of patients and PR in 16.7 %, yielding a final response rate of 75.0 %. The decrease in proteinuria was 43.1 ± 17.5 % after the first month of treatment (P < 0.001). Complete or PR was achieved in 6 of 8 patients with minimal change disease, 4 of 6 patients with mesangioproliferative glomerulonephritis (MsPGN), 6 of 7 patients with focal segmental glomerulosclerosis (FSGS), and all 2 patients with IgA nephropathy. Two patients (1 with MsPGN and 1 with FSGS) experienced relapses during the subsequent 6 months of follow-up. Adverse events included infection, hand tremor, diarrhea, acute reversible or persistent nephrotoxicity.

Conclusions: In conjunction with prednisone, TAC may be an alternative therapeutic regimen for adult SRNS patients. However, adverse events in these patients should be carefully monitored, especially at the beginning of treatment. Randomized controlled trials with longer follow-up are warranted.