Single-dose daily administration of cyclosporin A for relapsing nephrotic syndrome
Single-dose daily administration of cyclosporin A for relapsing nephrotic syndrome
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每日单剂量环孢素 A 治疗复发性肾病综合征
DOI：
10.1007/s00467-004-1508-y
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发表时间：
2004
影响因子：
3
通讯作者：
E. Ito
中科院分区：
文献类型：
--
作者：
Hiroshi Tanaka;T. Nakahata;E. Ito
环孢菌素A（CsA）已被报道是一种有效的类固醇节省剂在频繁复发性肾病综合征（FRNS）。然而，有时在选定的激素依赖性FRNS患者中观察到疗效较低。我们推测，低峰值水平的CsA在血液中可能是原因，并进行了一项前瞻性的试点研究，这些类固醇依赖性FRNS患者检查是否单剂量的CsA每日给药将产生足够的峰值血药浓度，因此，一个令人满意的类固醇节省的效果。5名7-16岁的激素依赖性FRNS儿童入组研究。所有患者均接受泼尼松龙联合CsA（T）每日两次治疗，由于类固醇节省效果较差，随后被每日单次给药方案（S）取代。虽然S方案的CsA平均日剂量显著低于T方案（S2.4±1.1 mg/kg/d vs.T3.6±0.8 mg/kg/d，P<0.05），但S方案的平均血药峰浓度倾向于高于T方案（S764±122 ng/ml vs.T358±250 ng/ml，P=0.1797），而平均血药谷浓度无升高。结果表明，维持临床缓解所需的最小泼尼松龙剂量，S组低于T组（S组0.4 ± 0.2mg/kg，隔日给药，T组0.6 ± 0.4mg/kg，隔日给药，P=0.0656）。1例患者在S方案开始后9个月进行的重复肾活检中未观察到CsA肾毒性的证据。这些临床观察结果，虽然对少数患者和初步的，表明单剂量的CsA每日给药可能是一个有吸引力的协议在选定的患者与类固醇依赖性FRNS中，CsA管理的传统协议是与一个穷人的类固醇节省效果。
Cyclosporin A (CsA) has been reported to be effective as a steroid-sparing agent in frequently relapsing nephrotic syndrome (FRNS). However, low efficacy has sometimes been observed in selected patients with steroid-dependent FRNS. We speculated that a low peak level of CsA in the blood might be the cause, and conducted a prospective pilot study on such steroid-dependent FRNS patients to examine whether single-dose daily administration of CsA would yield a sufficient peak blood level, and therefore a satisfactory steroid-sparing effect. Five children with steroid-dependent FRNS, aged 7–16 years, were enrolled in the study. All had been treated with prednisolone combined with twice daily CsA (T), which was subsequently replaced with the single-dose daily administration protocol (S), because of a poor steroid-sparing effect. Although the mean daily CsA dosage with theSprotocol was significantly lower than with theTprotocol (S2.4±1.1 mg/kg per day vs.T3.6±0.8 mg/kg per day,P<0.05), the mean peak blood level tended to be higher with theSprotocol than theTprotocol (S764±122 ng/ml vs.T358±250 ng/ml,P=0.1797) without mean trough blood level elevation. As a result, the minimum dose of prednisolone required for maintenance of clinical remission tended to be lower with theSthan theTprotocol (S0.4±0.2 mg/kg on alternate days vs.T0.6±0.4 mg/kg on alternate days,P=0.0656). No evidence of CsA nephrotoxicity was observed in a repeat renal biopsy performed 9 months after commencement of theSprotocol in one patient. These clinical observations, although on a small number of patients and preliminary, suggest that single-dose daily administration of CsA might be an attractive protocol in selected patients with steroid-dependent FRNS in whom CsA administration by the conventional protocol is associated with a poor steroid-sparing effect.