Tacrolimus versus cyclophosphamide in steroid-dependent or steroid-resistant focal segmental glomerulosclerosis: a randomized controlled trial.

BACKGROUND: The efficacy and safety of tacrolimus (TAC) and cyclophosphamide (CTX) were prospectively examined in steroid-dependent or steroid-resistant primary focal segmental glomerulosclerosis (FSGS).

METHODS: Patients with biopsy-proven FSGS were enrolled and randomly divided into two groups: CTX and TAC. Patients treated with CTX (0.5-0.75 g/m(2)·month, i.v.) received prednisone at 0.8 mg/kg·day, while patients treated with TAC (0.1 mg/kg·day) received prednisone at 0.5 mg/kg·day. The plasma concentration of TAC was monitored and maintained at 5-10 ng/ml. After a 6-month treatment the patients were evaluated. Patients with complete remission (CR) and partial remission (PR) continued the treatment for 12 months with the dose tapered, whereas the patients with no response were excluded from the study and underwent an alternative treatment.

RESULTS: A total of 33 patients were recruited and 27 completed the 12-month follow-up. The TAC-treated patients (n = 15) showed a quick remission. The initial remission time averaged 1.23 ± 0.21 versus 2.21 ± 0.77 months in the CTX group (n = 18), but no significant difference was achieved (p > 0.05). At 6 months, the two groups showed a similar outcome. Ten patients from each group showed remission (7 CR and 3 PR). At 12 months, the CTX group had 9 CR and 3 PR while the TAC group had 6 CR and 5 PR. Remission rates in TAC tended to be higher than that in CTX, but there was no difference. CTX patients had a high prevalence of infections (50.0 vs. 13.3% in TAC, p < 0.05). In contrast, TAC-treated patients showed a high incidence of hyperglycemia (26.7 vs. 0.0% in CTX, p < 0.05).

CONCLUSION: These results suggest that CTX and TAC had a similar efficacy in steroid-dependent and steroid-resistant FSGS as manifested by reduced proteinuria, improved serum albumin level and renal function.