Novel multidrug therapy for children with cyclosporine-resistant or -intolerant nephrotic syndrome
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ORIGINAL ARTICLE
Novel multidrug therapy for children with cyclosporine-resistant or -intolerant nephrotic syndrome Tomomi Aizawa-Yashiro & Kazushi Tsuruga & Shojiro Watanabe & Eishin Oki & Etsuro Ito & Hiroshi Tanaka
Received: 2 February 2011 / Revised: 15 March 2011 / Accepted: 16 March 2011 / Published online: 9 April 2011 # IPNA 2011
Abstract An effective treatment for children with refractory nephrotic syndrome (NS), especially in those with cyclosporine (CsA)-resistant or CsA-intolerant NS, has yet to be established. Recently, the efficacy of multidrug therapy consisting of tacrolimus (Tac), mycophenolate mofetil (MMF) in combination with prednisolone (PDN) in adult patients with refractory NS has been reported. We successfully treated 14 consecutive children with refractory CsA-resistant or CsA-intolerant NS using combination therapy consisting of relatively low-dose Tac, mizoribine (MZR), which has a mechanism of action very similar to that of MMF, and PDN. There were no serious clinical toxicities. Of the 14 children, 9 with a mean age of 13.0 years had steroid-dependent NS (SDNS) and 5 with a mean age of 9.6 years had steroid-resistant NS (SRNS). All SDNS patients had minimal change disease (MCD), 4 with SRNS had focal segmental glomerulosclerosis (FSGS), and the remaining child had MCD on renal biopsy. All patients were in a prospective cohort, but were evaluated retrospectively. The mean follow-up from the initiation of multidrug therapy was 18.4 months in SDNS and 18.6 months in SRNS patients. At the last observation point, the calculated relapse rate and minimum dose of PDN required for
maintenance of clinical remission after the start of multidrug therapy were significantly decreased compared with those prior to this therapy, while on CsA, in SDNS patients (0.4±0.5 times/year vs 2.9±1.5 times/year, P=0.0077, and 0.3±0.2 mg/kg on alternate days vs 0.5±0.2 mg/kg on alternate days, P=0.0184 respectively). All SDNS and two SRNS patients (40%) achieved complete remission, allowing further decreases in the minimal doses of PDN required for maintenance of clinical remission in most our patients. However, one patient with FSGS remained refractory to multidrug therapy and subsequently developed end-stage renal disease. These clinical observations, although preliminary and involving a small number of patients, suggest that multidrug therapy consisting of relatively low-dose Tac, MZR, and PDN might be effective and safe for treating children with refractory CsA-resistant or CsA-intolerant NS. However, further studies involving larger numbers of patients are needed. Keywords Cyclosporine-intolerant . Cyclosporineresistant . Mizoribine . Multidrug therapy . Refractory nephrotic syndrome . Tacrolimus
Introduction T. Aizawa-Yashiro : K. Tsuruga : S. Watanabe : E. Oki : E. Ito : H. Tanaka (*) Department of Pediatrics, Hirosaki University Hospital, Hirosaki 036-8563, Japan e-mail: [email protected] H. Tanaka Department of School Health Science, Faculty of Education, Hirosaki University, Hirosaki, Japan
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