Efficacy of once-daily cyclosporine in Japanese children with steroid-dependent minimal change nephrotic syndrome
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LETTER TO THE EDITOR
Efficacy of once‑daily cyclosporine in Japanese children with steroid‑dependent minimal change nephrotic syndrome Shuichiro Fujinaga1 · Tomohiko Nishino1 · Yasuko Urushihara1 Received: 11 August 2020 / Accepted: 15 September 2020 © Japanese Society of Nephrology 2020
To the Editor, Calcineurin inhibitor (CNI)-induced nephrotoxicity is still major concern regarding its long-term use, especially in children with a longer life expectancy and greater growth rate [1]. In a recent study on 21 French children with steroiddependent nephrotic syndrome (SDNS) who had received either tacrolimus or cyclosporine for a median of 30 months [2], CNI nephrotoxicity was found in only one patent who received twice-daily high-dose cyclosporine therapy (10 mg/ kg/day). The author concluded that infrequent CNI nephrotoxicity in their cohort could be explained by a greater use of tacrolimus. At present, however, we cannot utilize this CNI in clinical practice because the use of tacrolimus for children with SDNS is off-label among many countries, including Japan. Furthermore, one of the serious concerns with the use of tacrolimus is glucose intolerance. In the early 2010s, we reported that once-daily cyclosporine may be a simple and effective therapeutic option for children with SDNS [3, 4]. Since then, however, there have been no recent reports regarding the clinical outcomes of once-daily cyclosporine, especially in the incidence of chronic nephrotoxicity. Between January 2005 and April 2017, we retrospectively reviewed the record of 30 consecutive children (boys 26 and girl 4) who had initially received once-daily cyclosporine at Saitama Children’s Medical Center. Median age at NS onset was 6.6 (range 1.8–14.5) years and SDNS developed in all patients. Before the initiation of cyclosporine, mizoribine, and cyclophosphamide were administered in 10 and 11 patients, respectively. All patients had histological diagnosis of minimal change disease on pretreatment renal biopsies and were prescribed cyclosporine at a median age * Shuichiro Fujinaga [email protected] 1
Division of Nephrology, Saitama Children’s Medical Center, 1‑2 Shintoshin, Chuo‑ku, Saitama‑city, Saitama 330‑8777, Japan
of 9.2 (range 3.1–15.8) years. According to the therapeutic protocol reported previously, once-daily cyclosporine was adjusted to achieve a 2-h postdose cyclosporine (C2) levels of approximately 600 ng/mL. Treatment failure was defined as any condition requiring high-dose prednisolone (> 0.5 mg/kg or 15 mg) on alternate days to maintain remission, despite the initiation of once-daily cyclosporine. When patients developed treatment failure, they were subsequently switched to conventional twice-daily regimen to maintain C2 levels of 400–500 ng/mL. When patients had persistent steroid dependency after the twice-daily regimen, they received single infusion of rituximab (375 mg/m2). Post-treatment renal biopsies were performed in all patients after the longterm use of cyclosporine. After the initiation of once-daily cyclosporine,
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