钙调磷酸酶抑制剂长期治疗对Ⅴ型狼疮性肾炎患者肾功能的影响

The effect of long-term treatment with calcineurin inhibitors on renal function in patients with membranous lupus nephritis

目的:回顾性分析长期使用钙调磷酸酶抑制剂(CNI)对膜性狼疮性肾炎(MLN)患者的临床疗效及对血清肌酐(SCr)的影响。方法:收集2010年1月至2020年1月在国家肾脏疾病临床医学研究中心确诊为MLN的患者。根据CNI使用情况,分为长期治疗组、短期治疗组及未使用CNI组。观察CNI诱导期疗效,并比较三组患者基线临床病理特点及治疗期间SCr变化情况。结果:本研究共纳入456例MLN患者。平均随访78月,累积411例(90.1%)患者获得肾脏缓解,有297例患者使用CNI诱导治疗,缓解率84.2%。长期治疗组患者肾病综合征患者占比(P<0.001)、尿蛋白定量(P<0.001)、估算的肾小球滤过率(eGFR)(P<0.001)及血红蛋白(P=0.033)及总胆固醇(P=0.001)高于其他组,而年龄(P<0.001)、血清白蛋白(P<0.001)及球蛋白(P<0.001)更低;未使用CNI组的肾小球球性硬化比例(P=0.011)及慢性指数(P=0.016)更高,三组患者其他基线特征无统计学差异。至随访末,SCr较基线增高30.4%,三组SCr分别升高22.0%(67.18μmol/L vs 55.69μmol/L)、35.2%(76.02μmol/L vs 56.58μmol/L)和38.9%(92.82μmol/L vs 66.3μmol/L),三组SCr的增长率无统计学差异。结论:CNI诱导治疗MLN临床缓解率高,长期使用对SCr影响小。

Objective:To investigate the clinical efficacy of long-term use of calcineurin inhibitors(CNI)in patients with membranous lupus nephritis(MLN)and the effect on serum creatinine.Methodology:Patients with MLN diagnosed by renal biopsy at the National Clinical Research Centre of Kidney Diseases between January 2010 and January 2020 were enrolled in this study.According to the use time of CNI,the patients were divided into three groups:long-term treatment group,short-term treatment group and the non-CNI group.To observe the efficacy of patients in the induction period in the groups using CNI,the baseline clinicopathological characteristics of patients and changes in serum creatinine during the treatment period were compared among the three groups.Results:A total of 456 patients with MLN were followed for more than 6 months.At a mean follow-up of 78 months,a cumulative total of 411(90.1%)patients achieved renal remission,with 297 patients treated with CNI,for a remission rate of 84.2%.Patients in long-term treatment group had a higher percentage of patients with nephrotic syndrome(P<0.001),urinary protein(P<0.001),eGFR(P<0.001),and haemoglobin(P=0.033)and total cholesterol(P=0.001)than those in the other groups,whereas age(P<0.001),albumin(P<0.001)and globulin(P<0.001)were lower.The percentage of glomerulosclerosis(P=0.011)and the chronic index(P=0.016)were high in non-CNI group,and there were no significant differences in other baseline characteristics among the three groups.At the end of follow-up,serum creatinine increased by 30.4%from baseline,and serum creatinine in the three groups increased by 22.0%(67.18μmol/L vs 55.69μmol/L)、35.2%(76.02μmol/L vs 56.58μmol/L)and 38.9%(92.82μmol/L vs 66.3μmol/),respectively,with no significant difference between groups.Conclusion:CNI is the main therapeutic option for MLN,with a high remission rate on induction therapy and little effect on SCr with long-term use.