Calcineurin inhibitors (CNIs) are the preferred drugs for treatment of childhood steroid-resistant nephrotic syndrome (SRNS) who are also resistant to cyclophosphamide (CYC). Although few studies have shown a benefit of one over the other, efficacy and safety of either CNIs (tacrolimus [TAC] or cyclosporine [CSA]) in this special population remained to be assessed in long-term studies. Forty-five children with SRNS who were also resistant to CYC (CYC-SRNS) from January 2006 to June 2011, were included in the study. Patients were treated with CNI either TAC or CSA based on 1:1 allocations and were prospectively observed. Patients who were nonresponsive to CNIs had been treated with mycophenolate mofetil. Outcomes were measured in terms of remission of NS, adverse effects of drugs, and progression of disease. After 6 months of treatment, 16/23 (69.5%) patients on CSA achieved remission and 18/22 (81.8%) on TAC achieved remission (P = 0.3). The side effects hypertrichosis, and gum hyperplasia were significantly less in TAC group as compared to CSA group (P < 0.001). The 1-, 2-, 3-, 4-, and 5-year estimated renal survival (doubling of serum creatinine as event) in CSA group was 96%, 91%, 85%, 54%, and 33% and in TAC group was 96%, 95%, 90%, 89%, and 79%, respectively (P = 0.02). Although TAC and CSA are equally efficacious, TAC has significantly less side effects. The long-term outcome of renal function was significantly better in patients who were treated with TAC as compared to CSA.
Keywords: Cyclosporine; cyclophosphamide resistance; nephrotic syndrome; steroid resistance; tacrolimus.