来氟米特联合中小剂量激素治疗IgA肾病的疗效观察

目的 比较来氟米特联合中小剂量激素与足量激素治疗IgA肾病的短期与长期疗效及安全性评估。 方法 研究人群 18~65周岁，纳入标准 eGFR≥30 ml?min-1?(1.73 m2)-1且24 h尿蛋白量＞0.5 g的原发性IgA肾病患者。所有入选患者经计算机随机进入来氟米特联合中小剂量激素组（LEF组）和单用激素组（激素组）；研究的主要终点为：（1）进入ESRD或透析治疗；（2）Scr升高超过基线值的50%；次要终点为蛋白尿缓解。 结果 完成随访的患者共90例，LEF组40例，激素组50例，基线24 h尿蛋白量LEF组和激素组分别为2.00（1.10，2.88） g和1.87（1.13，3.08） g，两组患者尿蛋白在治疗6个月[分别为0.30（0.11，0.93） g，0.30（0.14，1.33） g]和12个月[分别为0.30（0.09，0.82） g，0.32（0.14，0.66） g]时较治疗前均有好转（P＜0.05）。激素组治疗后eGFR较治疗前升高[治疗前（80.39±28.56）、6个月（87.12±28.70）、12个月（88.20±30.26） ml?min-1?(1.73 m2)-1，P＜0.05]，LEF组eGFR治疗前后差异无统计学意义[治疗前（87.63±27.35）、6个月（86.91±32.45）、12个月（90.06±30.00） ml?min-1?(1.73 m2)-1，P＞0.05]，但治疗6个月及12个月时两组间比较尿蛋白、血肌酐、eGFR差异均无统计学意义（P＞0.05）。治疗期间两组不良反应发生率（LEF组9/40例，激素组11/50例）差异无统计学意义（P＞0.05）。平均随访79个月发现两组肾脏预后差异无统计学意义。Cox回归分析提示基线血肌酐及肾脏间质炎性细胞浸润程度是IgA肾病疾病进展的独立危险因素。 结论 来氟米特联合中小剂量激素对进展性IgA肾病的疗效与足量激素相当，治疗期间未增加不良事件发生率。

Leflunomide combined with medium/low dose corticosteroids vs full dose of corticosteroids in treatment of IgA nephropathy

Objective To compare the efficacy and safety of leflunomide (LEF) combined with medium/low dose corticosteroids and full dose of corticosteroids in the treatment of IgA nephropathy. Method Primary IgAN patients diagnosed by renal biopsy with 18-65 years old and eGFR≥30 ml?min-1?(1.73 m2)-1 and proteinuria＞0.5 g/24 h were enrolled in a prospective controlled clinical study. They were randomly divided into leflunomide combined with medium /low dose corticosteroids (LEF group) and corticosteroids alone (steroid group). The primary outcomes were (1) end stage renal disease or dialysis (2) 50% increase in serum creatinine above the baseline. Secondary outcome was the remission of proteinuria. Results Ninety patients completed the follow-up. The 24-hour proteinuria at baseline were 2.00(1.10, 2.88) g and 1.87(1.13，3.08) g in LEF group and steroid group respectively. Compared with baseline, it was significantly decreased in both groups at 6 months [0.30(0.11, 0.93) g, 0.30(0.14, 1.33) g] and 12 months [0.30(0.09, 0.82) g, 0.32(0.14, 0.66) g], (P＜0.05). Estimated glomerular filtration rate (eGFR) at baseline, 6 months and 12 months were (80.39±28.56), (87.12±28.70) and (88.20±30.26) ml?min-1?(1.73 m2)-1. It was decreased in steroid group (P＜0.05), while no significant difference was detected in LEF group[baseline (87.63±27.35), 6 months (86.91±32.45), 12 months (90.06±30.00) ml?min-1?(1.73 m2)-1, P＞0.05]. At 6 and 12 months, there was no significant difference in terms of 24-hour proteinuria, serum creatinine and eGFR (CKD-EPI) between groups (P＞0.05). There was no statistically significant difference in adverse events between groups during the treatment (9/40 cases in LEF group and 11/50 cases in steroid group, P＞0.05). The average follow-up was 79 months, and there was no difference in the renal prognosis between the two groups. Multivariate Cox regression analysis revealed that serum creatinine at baseline and renal interstitial inflammatory cell infiltration predicted the risk of the progress of IgA nephropathy. Conclusion Leflunomide plus medium/low dose corticosteroids has a similar effect as full dose of corticosteroids in IgA nephropathy and does not increase the risk for adverse events during the treatment.