Low-dose cyclosporine in treatment of membranous nephropathy with nephrotic syndrome: effectiveness and renal safety.
Low-dose cyclosporine in treatment of membranous nephropathy with nephrotic syndrome: effectiveness and renal safety.
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DOI：
10.1080/0886022x.2017.1373130
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发表时间：
2017-11
期刊：
影响因子：
3
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Yu X;Ruan L;Qu Z;Cui Z;Zhang Y;Wang X;Meng L;Liu X;Wang F;Zhang Y;Liu G;Yang L
背景：观察长期小剂量环孢素治疗特发性膜性肾病(IMN)的疗效和肾脏安全性。方法：68例患者参加了这项前瞻性队列研究。肾终点被定义为EGFR ≥较基线下降50%，并发展为EGFR≤60min/ /1.73m2。结果：环孢素2.0 ± 0.5 mg/kg/d，泼尼松0.3 ± 0.2 /kg/d。环孢素治疗时间为27(3~80)个月。总缓解率为91%，复发率为42%。14例患者在治疗前3个月内发生环孢素A相关性急性肾损伤(CsA-ARI)，16例患者在1年内发生环孢素A相关性慢性肾损伤(CsA-CRI)。随访结束时(50 ± 18 月)，16例(24%)达到肾终点。小动脉内膜纤维化的存在和较高的平均时间蛋白尿被确定为肾终点的独立危险因素。RAS抑制治疗降低了肾脏预后不良的风险。CsA-ARI组患者术后3个月尿蛋白最多，时均蛋白尿最多，达到肾终点的例数最高。CsA-CRI患者年龄最大，基线EGFR最低。结论：小剂量环孢素治疗特发性肾小球肾炎疗效确切。环孢素治疗前三个月CsA-ARI和蛋白尿无反应的受益/风险比最低，这些患者应该改用非钙调神经磷酸酶抑制剂的方案。年龄较大、基线EGFR较低或有小动脉内膜硬化的患者更容易发生进展性肾功能障碍。
Background: To observe effectiveness and renal safety of long-term low-dose cyclosporine in idiopathic membranous nephropathy (IMN). Methods: Sixty-eight patients were enrolled in this prospective cohort study. Renal endpoint was defined as a decrease in eGFR ≥50% from baseline and a development of eGFR ≤60 ml/min/1.73m2. Results: A cyclosporine dose of 2.0 ± 0.5 mg/kg/d and a prednisone of 0.3 ± 0.2 mg/kg/d were prescribed. The duration of cyclosporine treatment was 27 (3–80) months. The overall remission rate was 91% with a relapse rate of 42%. Fourteen patients had cyclosporine-related acute renal injury (CsA-ARI) within the first three months, and 16 patients had cyclosporine related chronic renal injury (CsA-CRI) within the first year. At the end of follow-up (50 ± 18 months), 16 patients (24%) reached renal endpoint. Presence of intimal fibrosis of small artery and higher time-averaged proteinuria were identified as independent risk factors for renal endpoint. RAS inhibition treatment decreased the risk of poor renal outcome. Patients in CsA-ARI group had the highest proteinuria at the third month, the highest time-average proteinuria and the highest proportion of cases reaching renal endpoint. Patients with CsA-CRI were of the oldest age and with the lowest baseline eGFR. Conclusions: Low-dose cyclosporine is effective in treating IMN. CsA-ARI and no response in proteinuria during the first three months of cyclosporine treatment had the lowest benefit/risk ratio, and these patients should be switched to non-calcineurin-inhibitor based regimen. Patients of older age, with lower baseline eGFR, or having intimal sclerosis of small artery, are more likely to develop progressive renal dysfunction.