【作者】 万利；

【导师】 郑法雷； 李明喜； 于阳；

【作者基本信息】 中国协和医科大学 ， 肾脏内科， 2008， 硕士

【摘要】 背景与目的马兜铃酸肾病(AAN)是马兜铃类中药引起的肾小管间质疾病,临床以慢性AAN最为多见,其病理以寡细胞性慢性肾间质纤维化为特征。迄今为止,对慢性AAN尚无成熟的治疗方案。近年国内外已有少量关于糖皮质激素治疗慢性AAN的报告,提示该治疗对延缓AAN进展有一定疗效。本文对轻中度肾衰及重度肾衰的慢性AAN患者应用小剂量糖皮质激素治疗,以观察该治疗对慢性AAN的病程有何有益作用。方法自2000年10月至2008年6月在北京协和医院肾内科诊治的慢性AAN患者共58例入组,根据治疗前血清肌酐分为轻中度肾衰组(Scr＜530umol/l,44例)与重度肾衰组(Scr＞530umol/l,14例)。轻中度肾哀组AAN患者分为激素治疗组(n=23)与对照组(n=21),两组患者的性别(女16/男7 vs女18/男3,P=0.287)、平均年龄(55.96±11.3岁vs56.19±13.2岁,P=0.950)、治疗前血清肌酐(334±98umol/l vs 292±95umol/l,P=0.153)均无显著差异。对1年的观察时间内两组患者的血清肌酐进行自身对照分析及两组间比较分析,以评价激素治疗对轻中度肾衰的慢性AAN的病程进展有无影响。重度肾衰组14例均接受激素治疗,女11例,男3例,平均年龄54.43±10.4岁,治疗前血清肌酐640±66umol/l。对1年的观察时间内该组患者血清肌酐进行自身对照分析,以评价激素治疗对重度肾衰的慢性AAN的病程进展有无影响。应用激素治疗的全部AAN患者为37例(女27例,男10例),平均年龄55.38±10.8岁,入组前血清肌酐为450±173umol/l。对糖皮质激素治疗的全部AAN患者的血清肌酐水平的变化进行自身对照分析,以评价激素治疗对慢性AAN病程进展的影响;同时对轻中度。肾衰组与重度肾衰组的血清肌酐变化情况进行比较分析,以评价不同程度肾衰的AAN患者从激素治疗中的获益有无差别。结果轻中度肾衰AAN患者中,激素治疗组在3个月、6个月、9个月、1年时的血清肌酐与治疗前比较无显著差异(P＞0.05),在最初3个月内血肌酐有所下降(300±78umol/l vs 334±98umol/l,P=0.196),3个月时Scr较治疗前下降33.6±4lumol/l(下降幅度8.2±11.4%),3个月后至1年内Scr维持稳定(1年后Scr为305±75umol/l)。对照组在6个月、9个月、1年时的血清肌酐与治疗前比较有显著升高(P均＜0.05),在1年的观察时间内,血肌酐呈持续性显著升高(411±167umol/l vs 292±95umol/l,P=0.031)。轻中度肾衰AAN患者中激素治疗组与对照组两组间比较,在6个月、9个月、1年时,激素治疗组的血清肌酐均显著低于对照组(各观察点P均＜0.05)。在1年内观察时间内,激素治疗组延缓加逆转的总有效率19例/20例(95%),对照组肾功能延缓加逆转的总有效率5/13例(38.5%),激素治疗组总有效率明显高于对照组(P＜0.001)。重度肾衰AAN患者在治疗后3个月、6个月、9个月、1年时,其血清肌酐水平与治疗前比较,均有显著下降(P均＜0.05)。在最初3个月内血肌酐下降明显(539±86umol/l vs 640±66umol/l,P=0.002),3个月时Scr较治疗前下降101±67umol/l(下降幅度15.7±10.6%),3个月后至1年内Scr维持稳定(1年后Scr为555±111umol/l)。应用激素治疗的全部慢性AAN患者在治疗后3个月、6个月、9个月、1年时的血清肌酐与治疗前比较无显著差异(P＞0.05),在最初3个月内血肌酐有所下降(393±143umol/l vs 450±173umol/l,P=0.130),3个月时Scr较治疗前下降60±61umol/l(下降幅度11.1±11.5%),3个月后至1年内Scr维持稳定(1年后Scr为399±151umol/l)。轻中度肾衰AAN患者与重度肾衰AAN患者接受激素治疗后,在治疗后3个月内重度肾衰组比轻中度肾衰组获益更明显(Scr下降数值101±67umol/l vs 33.6±41umol/l,P=0.003);3个月至1年内两组获益无显著差异;治疗前至治疗后1年内两组获益无明显差异(Scr下降数值87±126umol/l vs 28±70umol/1,P=0.158)。在1年的观察时间内,重度肾衰组延缓加逆转的总有效率为11例/12例(91.7%),轻中度肾衰组延缓加逆转的总有效率为19例/20例(95.5%),两组间有效率比较无显著差异(P=0.706)。治疗过程中的不良反应:轻中度肾衰AAN患者中激素治疗组有9例出现不良反应,4例类固醇性糖尿病、4例疱疹病毒感染、1股骨头坏死;重度肾衰AAN患者1例出现血糖升高。股骨头坏死发生在治疗后1年时,此后改例退出本研究。其余发生不良反应患者经对症治疗好转,仍坚持应用原治疗方案。结论对轻中度肾衰的慢性AAN患者应用小剂量糖皮质激素治疗,能逆转或延缓肾功能不全的进展,有明显保护肾功能的作用;重度肾衰AAN患者接受小剂量激素治疗亦能改善其肾功能。上述的激素保护作用在3个月内即出现,维持至少1年。重度肾衰组比轻中度肾衰组从激素治疗中获益在3个月内显著,1年内无明显差异。对AAN患者长期应用小剂量糖皮质激素治疗的安全性较好,大多数患者可以耐受。更多还原

【Abstract】 Background and ObjectiveAristolochic acid(AA)- induced kidney disease, aristolochic acid nephropathy(AAN), is characterized pathologically by chronic interstitial fibrosis with few cell infiltration. It is believed that chronic AAN is difficult to be cured with the routine treatment for chronic renal failure. In recent years, a few of reports suggested that glucocorticoid steroid could retard the progression of renal impairment in patients with ANN. In this study, we used low-dosage steroid therapy in ANN patients with mild-to-moderate and severe chronic renal failure to observe the effects of the steroid on the progression of renal failure in chronic AAN.Methods58 chronic AAN patients in Peking Union Medical College Hospital from October 2000 to July 2008 were included in this study. According to the levels of serum creatinine before treatment, the patients were divided into mild-to-moderate group(n=44, Scr < 530umol/l) and severe group(n=14, Scr> 530umol/l).The mild-to-moderate group was devided into steroid group(SG, n=23, prednisolone 0.5mg/kg for 1-3 month ,tapered off 0.04mg/kg every month) and control group(CG, n=21). The gender ratio, average age and serum creatinine levels before treatment were similar in the two groups. In the observation period of 1 year, the serum creatinine levels were compared between the SG and CG groups to examine the effects of steroid on renal failure progression of AAN.The patients of severe group(n=14) all accepted steroid therapy. The serum levels of crteatinine before and after 1 year treatment were compared to test the effects of steroid on the progression of renal failure of AAN.The serum creatinine levels of all patients who were given steroid therapy were compared before and after treatment to evaluate the impact of steroid on the progression of chronic AAN. At the same time, the creatinine levels of mild-to-moderate group was compared to that of severe group to determine whether there was any difference of the benefits which was obtained from steroid therapy between different degrees of renal failure.ResultsIn the mild-to-moderate group, the creatinine levels of the patients accepted steroid therapy at the month 3, 6, 9 and 12 after therapy were not significantly different compared with that before therapy, respectively. During the first 3 months, the serum creatinine levels were decreased, then kept steadily. While the renal function of the CG patients kept deteriorating and the creatinine levels were obviously higher than that of the SG patients. The results got from the severe group and all steroid-received patients resembled that of the the mild-to-moderate group .Our data also showed that during the first 3 months steroid therapy the decrease of creatinine levels in severe group were more significant than that in mild-to-moderate group, but there was no such difference for the whole 1 year.During the steroid therapy, 4 cases of DM, 4 cases of herpes infection, 1 case of femoral head necrosis occurred in the mild-to-moderate group, and 1 case of serum glucose increasing occurred in the severe group.ConclusionsLow-dosage seroids therapy could reverse or delay the progression of renal failure in AAN both for mild-to-moderate CRF and sever CRF. The protective effect mainly occured in the first 3 months, and kept at least for 1 year. The side effects of low-dosage seroid therapy were not severe and could be toleranced to the AAN patients.更多还原