Tacrolimus not superior to ciclosporin in pediatric steroid-dependent nephrotic syndrome

Original article

Sinha MD et al . (2006) Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus. Nephrol Dial Transplant  21 : 1848–1854  

Steroid-sparing regimens for the management of relapsing steroid-dependent nephrotic syndrome (SDNS) often include calcineurin inhibitors (CNIs). The newer CNI tacrolimus has been shown to be more effective than its predecessor ciclosporin in adults with SDNS, but data in pediatric populations are scarce.

A team from Guys Hospital in London , UK , report a retrospective longitudinal series of 10 children (median age at initial referral 3.9 years) with relapsing SDNS who visited the clinic at least once every 3 months. All patients initially responded to prednisolone. Subsequent relapses were treated first with cyclophosphamide, then with ciclosporin, intravenous mustine or a second course of cyclophosphamide. If relapses persisted, tacrolimus was prescribed. Kidneys were biopsied and glomerular filtration rates measured every 2–3 years over a total of 93 completed-treatment patient-years.

No significant differences were detected between ciclosporin and tacrolimus in terms of relapse rate (2 relapses/year vs 1 relapse/year, respectively), cumulative steroid dose (73.9 mg/kg/day vs 105.2 mg/kg/day, respectively), reduction in glomerular filtration rate (5.8 ml/min/ 1.73 m 2 vs 11.7 ml/min/ 1.73 m 2 , respectively) or median change in height. Three patients showed signs of mild CNI nephrotoxicity, and tacrolimus was discontinued in four children because of lack of response, glucose intolerance or hypertension. Antihypertensives were required for 11 of 31 ciclosporin treatment-years and for 22 of 40 tacrolimus treatment-years. The authors conclude that switching from ciclosporin to tacrolimus does not improve the management of severe SDNS in children.

在儿童的激素依赖型的肾病综合征的治疗中， 他克莫司并不优于环孢霉素A

Sinha MD et al . (2006) Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus. Nephrol Dial Transplant  21 : 1848–1854  

在复发的激素依赖型的肾病综合征的限制激素疗法中，通常包括钙调素的抑制剂 (CNIs) 。新型的钙调素抑制剂他克莫司在成人的激素依赖型的肾病综合征的治疗中显示了比其前一代药物环孢霉素更好的疗效，但是在儿童中的数据是缺乏的。

伦敦的 Guys 医院报道了一项对 10 个激素依赖型的肾病综合征的儿童纵向回顾性的研究，这些儿童的平均起始治疗年龄在 3.9 岁，最少每 3 个月随访一次。所有的病人最初对激素治疗都有反应，复发后起初用环磷酰胺，随后用环孢霉素、静注氮芥或第二疗程的环磷酰胺。如果仍复发就改用他克莫司。在 93 个完整的病人年中，每 2-3 年进行肾活检并评估肾小球滤过率。

结果是：环孢霉素和他克莫司在复发率（分别是 2 例 / 年和 1 例 / 年）、激素的累计剂量（分别是 73.9mg/kg/ 天和 105.2mg/kg/ 天）、 GFR 的恢复（分别是 5.8 ml/min/ 1.73 m 2 和 11.7 ml/min/ 1.73 m 2 ）和身高的中位数的变化在统计学上都没有显著性差异。 3 例病人出现了轻微的 钙调素抑制剂的肾毒性现象，4例病人因为对他克莫司治疗无反应、糖耐量异常或高血压而停药。在31个环孢霉素的 治疗年中有 11 个需要降压药物，而 40 个他克莫司治疗年有 22 个需要。所以作者认为将环孢霉素换成他克莫司并不能改善严重激素依赖型肾病综合征儿童的治疗。

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