不同剂量激素联合环孢素治疗特发性膜性肾病的临床研究

Clinical study on the treatment of idiopathic membranous nephropathy with different dosage of corticosteroid combined with cyclosporine A

目的观察不同剂量激素联合环孢素（CSA）治疗特发性膜性肾病（IMN）的疗效及不良反应。方法回顾性分析64例IMN肾病综合征（NS）患者，经肾内科门诊专人随访中位时间10（7，19）个月。据泼尼松用量分为2组：小剂量组32例，泼尼松（0．15mg·kg^-1·d^-1）＋CSA组；中剂量组32例，泼尼松（0．40—0．50mg·kg^-1·d^-1）＋CSA组。收集患者基线临床和病理资料、及治疗1、3、6个月后临床和化验资料；统计随访期间NS累计复发率和随访期间不良反应。结果两组患者在治疗后1、3、6个月时，血清白蛋白（sALB）较基线值均明显升高，24h尿蛋白量（24hUP）明显下降；Scr随治疗时间延长逐渐升高。中剂量组在治疗6个月时sALB升高、24hUP减少均高于小剂量组（均P〈0．05）。治疗6个月时，小、中剂量组有效率分别为65．6％和87．5％（r=4．267，P=0．039）。而比较不同剂量CSA在两组中治疗6个月时的疗效结果显示，小剂量组中CSA〈3mg·kg^-1·d^-1和〉3mg·kg^-1·d^-1有效率分别为76．5％和53．3％（P=0．296）；中剂量组中CSA〈3mg·kg^-1·d^-1和〉3mg·kg^-1·d^-1有效率分别为89．5％和84．6％（P=0．077）；两组患者中不同剂量CSA的疗效相当。随访结束时，49例缓解患者中20．4％患者复发，其中小、中剂量组复发率分别为9．5％和28．6％（P=0．136），多发生在泼尼松停药、环孢素减量过程中。随访结束时，不良反应发生情况两组间差异无统计学意义，其中。肾损害发生率为57．8％，小、中剂量组分别为50．0％和65．6％，主要见于老年人（9／11）和CSA疗程长者。在Scr超过基线值30％且峰值超过正常上线的14例肾损害患者中，与肾功能恢复患者相比，肾功能未恢复患者Scr峰值高（P〈0．05）、血环孢素谷浓度高。结论小剂量泼尼松（0．15mg·kg^-1·d^-1）联合环孢素治疗IMN患者6个月有效缓解率低于中剂量泼尼松（0．40～0．50mg·kg^-1·d^-1）组，复发率或不良反应发生率两组相当。环孢素〈3mg·kg^-1·d^-1诱导治疗IMN安全有效。老年人肾损害发生率高，而肾损害患者中Scr峰值高影响肾功能恢复。

Objective To evaluate the efficacy and safety of different doses of prednisone combined with cyclosporine A（CSA） on the treatment of idiopathic membranous nephropathy （IMN）. Methods The data of 64 patients with nephrotic syndrome （NS） diagnosed as IMN by renal biopsy were retrospectively analyzed. Median follow-up time was 10 （7, 19） months. The subjects were divided into 2 groups according to different prednisone dosage. Thirty-two cases were in the low-dose group： prednisone 0.15 mg·kg^-1·d^-1＋CSA, and 32 cases in the moderate-dose group： prednisone 0.4-0.5 mg·kg^-1·d^-1＋ CSA. Clinical and laboratory data were collected at baseline, 1, 3, and 6 months after treatment. During follow- up, cumulative recurrence rate and adverse reactions after treatment were recorded. Results Serum albumin （sALB） were significantly increased and 24 h urinary protein （24hUP） significantly decreased after treatment for 1, 3, 6 months compared with baseline data in the two groups. Serum creatine （Scr） increased after treatment with time. The elevation of sALB and the reduction of 24hUP in the moderate-dose group were higher than that of low-dose group at 6 months after treatment （P 〈 0.05）. The effective rate of the low-dose and moderate-dose group was 65.6% and 87.5% at 6 months after treatment, respectively （χ^2=4.267, P=0.039）. Comparison of different doses of CSA in two groups at 6 months after treatment, in low-dose group： the effective rates of CSA 〈 3 mg·kg^-1·d^-1 and 〉 3 mg·kg^-1·d^-1 subgroup were 76.5% and 53.3%, respectively （P=0.296）; In moderate- dose group： the effective rates of CSA 〈 3 mg·kg^-1·d^-1 and 〉 3 mg·kg^-1·d^-1 subgroup were 89.5% and 84.6%, respectively （P=0.077）; there were similar effects in patients treated with different dose CSA in the two groups. About 20.4% of the total patients relapsed when followed up for 18 months （low dose group vs moderate- dose group： 9.5% vs 28.6%, P=0.136）, which most occurred after prednisone withdrawal or during the reduction of cyclosporine. Renal function decreased in 57.8% patients （low dose group vs moderate-dose group： 50% vs 65.6%）, mainly in the elderly （9/11） and the long course of treatment of CSA. There was no significant difference on adverse reactions between the two groups （P 〉 0.05）. Renal function in patients with high Scr or high blood trough concentration of cyclosporine was difficult to fully recover. Conclusions Remission rate is lower in low-dose prednisone combined with cyclosporine than the moderate-dose group in the treatment of IMN for 6 months. The recurrence rate of IMN or the incidence of adverse reactions are similar between the two groups. Induction therapy of IMN with cyclosporin 〈 3 mg·kg^-1·d^-1 is safe and effective. The incidence of renal function reduction in the elderly is high, and the renal function is difficult to restore in patients with Scr exceeding normal upper limits.