Cao Qi, Huang Wen-yan, Xu Hong, Zhou Li-jun
Department of Nephrology, Pediatric Hospital, Fudan University, Shanghai 200032, China.
Zhonghua Er Ke Za Zhi. 2008 Sep;46(9):698-701.
To observe the effects of long-term cyclosporine A (CsA) treatment in 20 children with steroid-resistant idiopathic nephrotic syndrome (SRNS) and analyse the relevant influencing factors of CsA therapy.
Twenty children with SRNS received CsA therapy for 2 years between February 2001 and October 2006 in the Department of Nephrology. The mean age of children at initiation of CsA therapy was 5.5 years (30 months to 12 years). The initial renal histology showed minimal change (MCNS) in 15 patients, focal segmental glomerulosclerosis (FSGS) in 4 patients and mesangial proliferative glomerulonephritis (MsPGN) in one. The starting dose of CsA was 3 - 5 mg/(kg.d), adjusted to maintain a trough level of 100- 200 microg/L during the first 6 months. After one year, a low dose of CsA 1 - 3 mg/(kg.d) with a trough level of 40 - 70 microg/L was applied to maintain remission for 1 year. Liver function, serum albumin, serum cholesterol, serum creatinine, urinary NAG/Cr, 24 h urinary protein excretion and CsA whole blood trough level of the patients were monitored every one or three months.
(1) Complete remission (proteinuria < or = 0.1 g/d or negative by dipstick for 3 consecutive days), partial remission (proteinuria between 0.1 g/d and 50 mg/(kg.d), serum albumin > or = 30 g/L) and resistance to CsA (proteinuria > or = 50 mg/(kg.d), or > or = 3+ by dipstick, after 6 months of CsA treatment over a trough level of 100 microg/L) were observed in 65%, 20% and 15%, respectively. Eleven patients who had complete remission discontinued CsA, in 5 (45%) patients the disease relapsed, and resumption of CsA therapy was followed by remission in three of them. (2) MCNS showed a 93% response to CsA therapy while non-MCNS showed a 60% response, but the difference was not significant (P > 0.05). (3) Hypertrichosis, gingival hyperplasia and hypertension occurred in 75%, 25% and 10% of the patients, respectively. Two patients were found to have renal impairment (> 30% rise of serum creatinine) and recovered in 2 weeks. Four patients showed a rise of urinary NAG/Cr. The central nervous system adverse event occurred in 2 cases. Post-therapy biopsies performed in 3 patients (2 with FSGS and one with MCNS) did not show any relevant tubulointerstitial fibrosis. Two patients with FSGS of the twenty cases progressed into end-stage renal failure.
CsA treatment was confirmed to be effective in children with SRNS. Renal fibrosis was rare in patients treated with a low dose of CsA for 2 years.
观察长期应用环孢素A（CsA）治疗20例激素抵抗型特发性肾病综合征（SRNS）患儿的疗效，并分析CsA治疗的相关影响因素。
2001年2月至2006年10月，20例SRNS患儿在肾内科接受CsA治疗2年。开始CsA治疗时患儿的平均年龄为5.5岁（30个月至12岁）。初始肾组织学检查显示，15例为微小病变（MCNS），4例为局灶节段性肾小球硬化（FSGS），1例为系膜增生性肾小球肾炎（MsPGN）。CsA起始剂量为3 - 5mg/（kg·d），在最初6个月调整剂量以维持谷浓度在100 - 200μg/L。1年后，应用低剂量CsA 1 - 3mg/（kg·d），谷浓度维持在40 - 70μg/L，维持缓解1年。每1或3个月监测患者的肝功能、血清白蛋白、血清胆固醇、血清肌酐、尿NAG/Cr、24小时尿蛋白排泄量及CsA全血谷浓度。
（1）完全缓解（蛋白尿≤0.1g/d或连续3天试纸法检测为阴性）、部分缓解（蛋白尿在0.1g/d至50mg/（kg·d）之间，血清白蛋白≥30g/L）及CsA抵抗（CsA治疗6个月后，谷浓度>100μg/L时，蛋白尿≥50mg/（kg·d）或试纸法检测≥3+）的发生率分别为65%、20%和15%。11例完全缓解的患者停用CsA，其中5例（45%）疾病复发，3例再次应用CsA治疗后缓解。（2）MCNS对CsA治疗的反应率为93%，非MCNS为60%，但差异无统计学意义（P>0.05）。（3）75%、25%和10%的患者分别出现多毛症、牙龈增生和高血压。2例患者出现肾功能损害（血清肌酐升高>30%），2周后恢复。4例患者尿NAG/Cr升高。2例发生中枢神经系统不良事件。3例患者（2例FSGS和1例MCNS）治疗后肾活检未显示任何相关的肾小管间质纤维化。20例中有2例FSGS患者进展为终末期肾衰竭。
CsA治疗SRNS患儿有效。低剂量CsA治疗2年的患者肾纤维化少见。
