Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: current status and future directions

Abstract

Clinicians are often faced with therapeutic dilemmas and challenges while treating children with frequently relapsing steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS). In the past, children with SDNS have been treated with long-term alternate day steroids cyclophosphamide, cyclosporine (CSA), chlorambucil, levamisole, and azathioprine. The essential aim of these therapies is to maintain remission while limiting exposure to steroids. These medications have variable efficacy and undesirable toxicity profiles. Recently, mycophenolate mofetil (MMF) has emerged as a new therapeutic option for the management of SDNS in a few uncontrolled clinical trials. Preliminary data are encouraging. MMF was found to be useful in maintaining remission and has a steroid-sparing effect. Clearly, more data are needed to further characterize the safety and efficacy of MMF, define adequate length of treatment, and optimize drug exposure and monitoring. The management of SRNS is primarily aimed at decreasing proteinuria and inducing remission, if possible. By doing so, one would aim to preserve renal function. CSA therapy is known to be useful in this regard but has undesirable side effects, the most concerning being nephrotoxicity. MMF in combination with steroids and angiotensin-converting enzyme-inhibitor drugs is known to have some efficacy in the management of SRNS. These preliminary data have prompted the National Institutes of Health to sponsor a multicentric controlled trial to compare the safety and efficacy of MMF with that of CSA in the treatment of steroid-resistant focal segmental glomerulosclerosis (FSGS). If MMF therapy is found to be efficacious, it would help obviate the need for CSA and its associated nephrotoxicity. Clearly, MMF has emerged as an important new therapeutic option for the treatment of childhood nephrotic syndrome and FSGS. Further data are required to assess those conditions most likely to respond.

Mycophenolate mofetil monotherapy in the management of paediatric uveitis

“…[14][15][16] MMF has also been proven effective in autoimmune diseases in children. [17][18][19][20] Here, we report our experience with MMF in paediatric patients with autoimmune uveitis.…”

“…Nine of them achieved inflammation control on MMF without concomitant corticosteroids or other IMTs for a median of 15 months (range: [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. During this follow-up period, 8 out of the 9 patients experienced no uveitis relapse; 1 patient experienced one relapse that was treated with 4 weeks of topical corticosteroids.…”

Immunosuppression and Renal Outcome in Congenital and Pediatric Steroid-Resistant Nephrotic Syndrome

“…Numerous immunosuppressive agents have shown to be effective in a subset of SRNS patients (8,9). Cyclosporine A (CsA) is used preferentially and several studies demonstrated CsA-induced remission rates (including partial remission) of up to 70% in pediatric SRNS patients (10 -12).…”

Mycophenolate mofetil for primary focal segmental glomerulosclerosis: systematic review

“…Overall, relapse rate after discontinuation of cyclosporine was 67%; and that of corticosteroids was 55%. 1,18 In recent years, mycophenolate mofetil (MMF) (brand names: CellCept), 19 originally approved by the FDA as an immunosuppressant for transplant patients, 20 has become a novel choice for primary FSGS patients who have exhausted these two frontline treatment options. MMF acts through its inhibition on the inosine monophosphate dehydrogenase, which reduces T and B lymphocyte proliferation.…”