Second-line immunosuppressive treatment of childhood nephrotic syndrome: a single-center experience.

Objective: Most cases of idiopathic nephrotic syndrome in childhood are responsive to corticosteroids. However, there is a small group of children that demonstrate steroid resistance (steroid-resistant nephrotic syndrome; SRNS), steroid dependence, or that frequently relapse (frequent-relapse steroid-sensitive nephrotic syndrome; FR-SSNS) which are more clinically difficult to treat. Therefore, second-line immunosuppressants, such as alkylating agents, calcineurin inhibitors, antimetabolites and, more recently, rituximab, have been used with varying success. The objective was to evaluate the response rates of various second-line therapies in the treatment of childhood nephrotic syndrome.

Study design: A retrospective chart review of pediatric subjects with idiopathic nephrotic syndrome was conducted at a single tertiary care center (2007-2012). Drug responses were classified as complete response, partial response, and no response.

Results: Of the 188 charts reviewed, 121 children were classified as SSNS and 67 children as SRNS; 58% were classified as FR-SSNS. Sixty-five subjects were diagnosed with focal segmental glomerulosclerosis via biopsy. Follow-up ranged from 6 months to 21 years. The combined rate of complete and partial response for mycophenolate mofetil (MMF) was 65% (33/51) in SSNS and 67% (6/9) in SRNS. For tacrolimus, the response rate was 96% (22/23) for SSNS and 77% (17/22) for SRNS. Eighty-three percent (5/6) of SSNS subjects treated with rituximab went into complete remission; 60% relapsed after B-cell repletion. Eight refractory subjects were treated with combined MMF/tacrolimus/corticosteroid therapy with a 75% response rate.

Conclusion: Our experience demonstrates that older medications can be replaced with newer ones such as MMF, tacrolimus, and rituximab with good outcomes and better side effect profiles. The treatment of refractory cases with combination therapy is promising.