环孢素治疗成人特发性膜性肾病肾病综合征：一项跨越 15 年的回顾性研究。

Cyclosporine treatment in idiopathic membranous nephropathy nephrotic syndrome in adults: a retrospective study spanning 15 years.

机构信息

Division of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.

出版信息

Chin Med J (Engl). 2011 Nov;124(21):3490-4.

PMID:22340164

Abstract

BACKGROUND

Cyclosporine is effective in treating nephrotic syndrome (NS) with idiopathic membranous nephropathy (IMN) in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is inconclusive. The aim of this study was to introduce the way how to titrate the cyclosporine to maintain complete remission without relapse.

METHODS

Patients with biopsy-proven IMN with NS treated with cyclosporine for at least 1 month from 1996 to 2011 at Peking Union Medical College Hospital were reviewed.

RESULTS

Mean age of the 51 eligible patients was 52 years, with 39 men. Mean proteinuria was (7.47 ± 3.14) g/d, serum albumin (24.50 ± 6.29) g/L, and serum creatinine (82.62 ± 21.18) mmol/L. Cyclosporine was commenced at a mean dose of (3.46 ± 0.63) mg×kg(-1)×d(-1). Oral prednisone (0.40 ± 0.29) mg×kg(-1)×d(-1) was given concomitantly in 38 patients. Cyclosporine was administered for a median of 16 months (range 1 - 93 months) and stopped in non-responders by month six. By month 3 (n = 47), the number in complete remission (CR) and partial remission (PR) was 3 and 24, which shifted to 12 and 17 by month 6 (n = 41). Male gender, heavy proteinuria, low serum albumin level, and high serum creatinine level were significant determinants in poor response by month six (P < 0.05 in all variables compared with responders). There was a significant reversible serum creatinine increase within 25% during month 3 to 12 (P < 0.05 in all variables compared with baseline value). Eleven patients maintained cyclosporine for more than 24 months with a cyclosporine dose of (1.04 ± 1.06) mg×kg(-1)×d(-1). Nine patients were in CR. Renal function, systolic and diastolic blood pressure remained stable. Renal impairment (> 30% rise of serum creatinine), secondary infection, hypertension, gingival hyperplasia and liver impairment occurred in 6, 4, 10, 4, and 1 patients, respectively.

CONCLUSIONS

The observation time for cyclosporine to effectively induce CR of NS in IMN adults should be at least six months. Long-term and low-dose of cyclosporine therapy is safe and effective to maintain CR in those responders.

摘要

背景

环孢素治疗特发性膜性肾病（IMN）成人肾病综合征（NS）有效，但高复发率仍是一个主要问题。环孢素的使用方法尚无定论。本研究旨在介绍如何调整环孢素的剂量以维持完全缓解而不复发。

方法

回顾了 1996 年至 2011 年期间在北京协和医院接受环孢素治疗至少 1 个月的活检证实为 IMN 伴 NS 的 51 例患者。

结果

51 例符合条件的患者平均年龄为 52 岁，其中 39 例为男性。平均蛋白尿为（7.47 ± 3.14）g/d，血清白蛋白（24.50 ± 6.29）g/L，血清肌酐（82.62 ± 21.18）mmol/L。环孢素起始剂量为（3.46 ± 0.63）mg·kg(-1)·d(-1)。38 例患者同时给予口服泼尼松（0.40 ± 0.29）mg·kg(-1)·d(-1)。中位环孢素治疗时间为 16 个月（范围 1-93 个月），无应答者在 6 个月时停药。在第 3 个月（n = 47），完全缓解（CR）和部分缓解（PR）的人数分别为 3 和 24，在第 6 个月（n = 41）时分别为 12 和 17。男性、大量蛋白尿、低血清白蛋白水平和高血清肌酐水平是 6 个月时应答不良的显著决定因素（与应答者相比，所有变量的 P 值均<0.05）。第 3 个月至第 12 个月期间，血清肌酐有显著的可逆性增加（与基线值相比，所有变量的 P 值均<0.05），增加幅度为 25%。11 例患者维持环孢素治疗超过 24 个月，环孢素剂量为（1.04 ± 1.06）mg·kg(-1)·d(-1)。9 例患者达到 CR。肾功能、收缩压和舒张压保持稳定。6 例患者出现肾功能损害（血清肌酐升高>30%），4 例出现继发性感染，10 例出现高血压，4 例出现牙龈增生，1 例出现肝功能损害。