Risk of persistent steroid dependency after switching from cyclosporine to mycophenolate mofetil in children with idiopathic nephrotic syndrome.

Abstract

Sir, We read with great interest the article BMorbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial^ by Ishikura et al., which was recently published in Pediatric Nephrology [1]. In a longterm follow-up study of 46 Japanese children with frequently relapsing nephrotic syndrome (FRNS), after an initial 2-year treatment of cyclosporine (CsA), these authors showed that half of the patients still continued to relapse frequently or were on immunosuppressive agents at the last observation (mean age 18.7 years). They also found that 27 of the 46 patients (59 %) had been restarted on or continued to take CsA during the follow-up period (median 10.3 years), while no patients had received mycophenolate mofetil (MMF). In another longterm follow-up study, Banerjee et al. reported the outcome in 46 Indian patients with nephrotic syndrome (NS) receiving MMF who remained steroid dependent (SD) despite prior treatment with levamisole and cyclophosphamide [2]. At a mean follow-up of 3.56 years, 25 of these patients (54 %) required no further alternative immunosuppression, having infrequent or no relapses of NS. These authors concluded that MMF treatment allowed >50 % of patients with severe SDNS to avoid further treatment with toxic immunosuppressive agents, such as CsA, in the long term. Based on our experience at a single center, we would like to comment on the risk of persistent steroid dependency after switching patients with childhood-onset idiopathic NS from CsA to MMF. Between March 2005 and October 2012, we recruited 52 patients (37 boys, 15 girls; median age 12.2 years) with SDNSwho initially receivedMMF at Saitama Children’s Medical Center due to NS relapses during or after CsA treatment. The median age of the patients at NS diagnosis was 5.5 years. They all developed SDNS (36 patients) or steroidresistant nephrotic syndrome (SRNS, 16 patients) and were initially prescribed CsA for a median period of 39.5 months before being started on MMF. Prior to CsA treatment, 17 of these patients had received cyclophosphamide. Despite being started on therapy with CsA, 12 patients required rituximab infusions due to persistent steroid dependency. Histological analysis showed minimal change disease in 47 of the patients and focal segmental glomerulosclerosis in five patients. The MMF dose was adjusted to maintain a target predose mycophenolic acid level of 2–5 μg/mL (maximum 2 g/day). Relapses were treated with 2 mg/kg/day of prednisolone until proteinuria was not detected for >3 consecutive days; thereafter, prednisolone was administered on alternate days, with the dose tapered off within 6 months. MMFwas also tapered off if prednisolone had been stopped for at least 12 months. When patients developed SDNS once again after they had stopped receiving MMF, those without CsA nephrotoxicity were retreated with CsA and those with CsA nephrotoxicity were treated with MMF or high-dose mizoribine. During the follow-up period (median 6.1 years) after the initiation of therapy with MMF (median duration of MMF treatment 46.7 months), only three of the 52 patients did not experience a relapse of NS, 14 were re-treated with CsA and 27 received rituximab infusions. At the last follow-up (median age 18.3 years), 19 patients (37 %, group A) did not require any immunosuppressive agent, while 33 patients (63 %, group B) continued to receive therapy with immunosuppressive agents (MMF, 27 patients; CsA, 5 patients; mizoribine, 1 patient) * Shuichiro Fujinaga f_shuich@d2.dion.ne.jp