CAJ | 학술논문

目的：观察他克莫司治疗IgA肾病（IgA nephropathy, IgAN）的长期疗效和安全性。方法：回顾性分析我科IgAN随访队列中应用他克莫司治疗并且随访时间>1年的原发性IgAN患者，观察用药及随访期间患者尿蛋白定量、血清白蛋白水平及估算肾小球滤过率（eGFR）的变化，并评价用药相关不良事件。结果：共21例IgAN患者纳入本研究，平均年龄（29.4±10.6）岁，平均随访时间为（54.0±35.8）月，所有患者在应用他克莫司之前均应用了ACEI/ARB和/或激素免疫抑制治疗，且尿蛋白仍＞1 g·d-1，应用他克莫司前的平均尿蛋白（4.84±2.40）g·d-1，平均eGFR（78.33±37.30） mL·min-1·1.73 m-2。5/21例eGFR（34.70±9.67）mL·min-1·1.73 m-2的患者在用药1~1.5月后因eGFR下降＞15%而停药，其余16/21例患者用药时间≥6个月，其中13/16例（81.3%）在治疗平均（5.31±3.35）周时获得蛋白尿缓解，包括12例完全缓解和1例部分缓解，8/13例获得缓解的时间在应用他克莫司治疗后的4周内，患者用药前与治疗结束时的eGFR差异没有统计学意义（93.5±32.8）vs（80.4±32.5）mL·min-1·1.73m-2，P =0.27）。6/13例（46.2%）在他克莫司减量或停药后出现复发。用药相关不良事件包括感染（2例），新发高血压（1例），高尿酸血症（3例）等。结论：①他克莫司在对ACEI/ARB和/或激素免疫抑制治疗效果不佳的IgAN治疗中显现出快速的蛋白尿缓解趋势，但在CKD 3期以上的患者中应慎重使用。②他克莫司在减量或停药过程中复发率较高。
목적：관찰타극막사치료IgA신병（IgA nephropathy, IgAN）적장기료효화안전성。방법：회고성분석아과IgAN수방대렬중응용타극막사치료병차수방시간>1년적원발성IgAN환자，관찰용약급수방기간환자뇨단백정량、혈청백단백수평급고산신소구려과솔（eGFR）적변화，병평개용약상관불량사건。결과：공21례IgAN환자납입본연구，평균년령（29.4±10.6）세，평균수방시간위（54.0±35.8）월，소유환자재응용타극막사지전균응용료ACEI/ARB화/혹격소면역억제치료，차뇨단백잉＞1 g·d-1，응용타극막사전적평균뇨단백（4.84±2.40）g·d-1，평균eGFR（78.33±37.30） mL·min-1·1.73 m-2。5/21례eGFR（34.70±9.67）mL·min-1·1.73 m-2적환자재용약1~1.5월후인eGFR하강＞15%이정약，기여16/21례환자용약시간≥6개월，기중13/16례（81.3%）재치료평균（5.31±3.35）주시획득단백뇨완해，포괄12례완전완해화1례부분완해，8/13례획득완해적시간재응용타극막사치료후적4주내，환자용약전여치료결속시적eGFR차이몰유통계학의의（93.5±32.8）vs（80.4±32.5）mL·min-1·1.73m-2，P =0.27）。6/13례（46.2%）재타극막사감량혹정약후출현복발。용약상관불량사건포괄감염（2례），신발고혈압（1례），고뇨산혈증（3례）등。결론：①타극막사재대ACEI/ARB화/혹격소면역억제치료효과불가적IgAN치료중현현출쾌속적단백뇨완해추세，단재CKD 3기이상적환자중응신중사용。②타극막사재감량혹정약과정중복발솔교고。
Objective:To investigate the clinical efifcacy and adverse reaction of tacrolimus in the treatment of IgA nephropathy.Methods:Biopsy-proven IgA nephropathy patients who had been treated with tacrolimus and with follow-up time more than 1-year in Renal Division Peking University First Hospital, were enrolled in this retrospective study. Urinary protein excretion, serum albumin levels, glomerular ifltration rate (eGFR), and tacrolimus related adverse events during the treatment and follow-up were evaluated.Results: A total of 21 patients with mean age (29.4 ± 10.6) years were analyzed. The mean follow-up time was (54.0 ± 35.8) months. All patients had been treated with ACEI/ARB and/or immunosuppressive therapy before tacrolimus therapy, and their urinary protein excretion were still more than 1g·d-1. Before tacrolimus therapy, the mean urinary protein excretion was (4.84±2.40) g·d-1 and mean eGFR was (78.33±37.30) mL·min-1·1.73m-2. 5/21 patients with mean eGFR (34.70±9.67) mL·min-1·1.73m-2 withdrew tacrolimus treatment within 1~1.5 months, because of more than 15% of eGFR decline. For 16 patients who were treated with tacrolimus more than 6 months, 13/16 cases (81.3%) achieved proteinuria remission, including 12 cases of complete remission and 1 case of partial remission. Mean times to achieve remission were (5.31±3.35) weeks. 8/13 cases achieved remission in 4 weeks. The level of eGFR before and after tacrolimus treatment withdrawal didn’t change signiifcantly in 16 cases (93.5±32.8) vs (80.4±32.5) mL·min-1·1.73m-2,P = 0.27). In patients who achieved complete or partial remission, 46.2% experienced relapse during follow-up. Other adverse events included infection (2 cases), new-onset hypertension (1 case) and hyperuricemia (3 cases).Conclusion:①Tacrolimus showed a rapid proteinuria remission in IgAN patients with ACEI/ARB and/or hormone immunosuppressive therapy resistance, but it should be used cautiously in patients with CKD stage 3.②There was a high relapse rate during tapering or cessation of tacrolimus therapy.