小剂量环孢素A联合小剂量泼尼松治疗特发性膜性肾病的初步观察

目的 非随机前瞻性观察小剂量环孢素A（CsA）联合小剂量泼尼松在我国特发性膜性肾病治疗中的疗效及不良反应，比较其与环磷酰胺（CTX）联合足量泼尼松的异同。 方法 31例经肾活检病理证实为特发性膜性肾病（Ⅰ~Ⅲ期）的肾功能正常的大量蛋白尿患者纳入本研究。CTX组20例，100 mg/d, 累积量约8 g；口服泼尼松0.6~1.0 mg•kg-1•d-1，2～3个月后逐渐减量。CsA 组19例（包括CTX组中治疗无效或复发的8例），起始量1.0~1.5 mg•kg-1•d-1，2～3个月无效者，逐渐加量，最大剂量≤2.5 mg•kg-1•d-1；口服泼尼松0.15~0.50 mg•kg-1•d-1，3月个后逐渐减量。观察两组治疗前后的尿蛋白、血白蛋白和血肌酐等疗效指标及不良反应。 结果 CTX组随访（48±22）周，13例有效(65%，7例部分缓解，6例完全缓解)，7例无效(35%)。CsA组随访（44±15）周，其中2例因不良反应而退出，余17例中，12例有效(70%，6例部分缓解，6例完全缓解)，5例无效(30%)。两组缓解比例的差异无统计学意义。CTX组的不良反应有肝功能损伤等。CsA组的不良反应有血肌酐上升（3例）、高血压（12例）等，停药后或用药可控制。 结论 小剂量CsA联合小剂量泼尼松与CTX联合足量泼尼松治疗特发膜性肾病的缓解比例相近，对于CTX治疗无效或复发的患者，仍可能有效，虽然不良反应较多，但易于监测和控制。

Preliminary observation of low-dose cyclosporine A combined with low-dose prednisone in the treatment of patients with idiopathic membranous nephropathy

Objective To evaluate the efficacy and safety of low-dose cyclosporine A (CsA) combined with low-dose prednisone as induction therapy for patients with idiopathic membranous nephropathy (IMN) and compare with those of cyclophosphamide (CTX) combined with high-dose prednisone.Methods A prospective observational cohort study in 31 nephrotic patients with IMN was conducted.In CTX group,patients were treated with cyclophosphamide (oral 100 mg/d,accumulation about 8 g) combined with prednisone (0.6-1.0 mg·kg~(-1)·d~(-1),tapered after 2-3 months).In CsA group,initial dose of CsA was 1.0-1.5 mg·kg~(-1)·d~(-1) combined with prednisone 0.15-0.50 mg·kg~(-1)·d~(-1)(0.33±0.20) mg·kg~(-1)·d~(-1),tapered after 3 months].The dose of CsA was added gradually according to efficacy and the highest dose of cyclosporine was ≤2.5 mg·kg~(-1)·d~(-1).Clinical parameters (urinary protein,serum albumin and serum creatinine) and adverse effects were estimated before and after therapy.ResultsIn CTX group,twenty patients had been followed-up for (48±22) weeks and their remission was observed in 13 patients (65%,complete remission 6,partial remission 7).Nineteen patients were recruited in CsA group,including 8 patients who either had no response or relapsed after CTX therapy.In CsA group,two patients discontinued CsA therapy due to severe uncontrolled hypertension;the effective dose of CsA for remission was (2.1±0.4) mg·kg~(-1)·d~(-1) (1.5-2.5 mg·kg~(-1)·d~(-1));mean trough concentration of CsA was (92.5±23.5) μg/L (58-124 μg/L);remission was observed in 12 patients (70%,complete remission 6,partial remission 6) over a period of (44±15) weeks.There was no significant difference of remission rate between two groups.Liver dysfunction was common adverse effects during CTX therapy.Many adverse effects (increase of serum creatinine,hypertension,gum hyperplasia and hyperuricemia) occurred during CsA therapy,but could be easily controlled.Conclusions Low-dose CsA combined with low-dose prednisone has similar efficacy and safety to CTX combined with high-dose prednisone for majority of patients with IMN,including refractory patients to CTX regimens.Many adverse effects occur during CsA therapy,but can be easily controlled.