摘要
目的比较单纯糖皮质激素治疗与糖皮质激素联合环磷酰胺(CTX)治疗对原发性免疫球蛋白A(IgA)肾病(IgAN)伴肾病综合征和肾功能不全患者的疗效。方法选择上海交通大学医学院附属瑞金医院肾脏内科2004年1月—2010年5月经肾穿刺活组织病理检查确诊为原发性IgAN的患者110例,合并肾病综合征,同时伴或不伴肾功能不全。将患者分为单纯激素组和激素联合CTX组,每组55例。单纯激素组:伴肾功能损伤者29例,肾功能无明显损伤者26例;予泼尼松0.8～1mg·kg-1·d-1,12周后每3～4周减原剂量的10%～15%,直至维持剂量10～15mg/d,继续治疗24周。激素联合CTX组:伴肾功能损伤者32例,肾功能无明显损伤者23例;激素用法同单纯激素组;予CTX0.5～0.75g·m-2·次-1,每4周1次,治疗6次后,改为每8周1次,治疗3次。伴有高血压的患者可以应用血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂类药物。随访时间为36个月,比较两组患者的临床基线特征和病理资料,监测患者的血白蛋白、24h尿蛋白定量和血清肌酐水平,比较单纯激素与激素联合CTX治疗伴或不伴肾功能损伤的IgAN患者的疗效及临床预后。结果各组间年龄、性别构成、高血压发生率、血尿发生率、血白蛋白、24h尿蛋白定量和血清肌酐水平,球性硬化、系膜增生、新月体形成、间质硬化、小管萎缩、血管病变所占百分率等评分方面的差异均无统计学意义(P值均>0.05)。伴肾功能损伤的患者中,从随访第3个月开始,单纯激素组和激素联合CTX组的血白蛋白水平均较基线水平显著升高(P值均<0.05),24h尿蛋白定量水平均较基线水平显著降低(P值均<0.05)。随访期间,单纯激素组的血清肌酐水平与基线水平的差异无统计学意义(P>0.05);随访第24和36个月,激素联合CTX组的血清肌酐水平均较基线水平显著升高(P值均<0.05)。肾功能无明显损伤的患者中,从随访第3个月开始,单纯激素组和激素联合CTX组的血白蛋白水平均较基线水平显著升高(P值均<0.05),24h尿蛋白定量水平均较基线水平显著降低(P值均<0.05)。随访期间,两组间血清肌酐水平与基线水平的差异均无统计学意义(P值均>0.05)。治疗期间,两组的安全性均较好,其中单纯激素组出现糖耐量异常2例,在激素减量后好转;肝功能损伤1例,经保肝治疗后肝功能恢复正常。激素联合CTX组出现骨质疏松1例,糖耐量异常2例。两组均未出现严重感染等不良反应。结论在肾功能不全的IgAN肾病综合征患者中应用细胞毒类药物治疗,与单纯糖皮质激素治疗相比,均可明显减少蛋白尿,缓解肾病综合征,但尚无充分的研究证据表明CTX的应用对改善患者预后及延缓肾功能减退有益。
Objective To compare the clinical outcomes of prednisone therapy with prednisone plus cyclophosphamide therapy for IgA nephropathy （IgAN） combined with impaired renal function and nephrotic syndrome. Methods A total of 110 patients with renal biopsy-proven IgAN and nephrotic syndrome in Shanghai Ruijin Hospital from January 2004 to May 2010 were enrolled in this study. The patients were divided into steroid group （n=55, eGFR〈70 mL min-1 1.73 m-2 in 29 and eGFR 70 mE min-1 1.73 m-2 in 26） and prednisone plus cyclophosphamide group （n=55, eGFR〈70 mL min-1 1.73 m-2 in 32 and eGFR70 mL min-1 1.73 m-2 in 23）. Prednisone usage= 0.8- 1 mg kg-1 d-1 for 12 weeks, then decresed 10% - 15% every 3 or 4 weeks until 10 - 15 mg/d for another 24 weeks. Cyclophosphamide usage： 0.5- 0.75 g/m2 , every 4 weeks for 6 times, then every 8 weeks for 3 times. ACEI or ARB could be used in hypertension patients. The mean follow-up period was 36 months. Serum albumin, 24-hour proteinuria and serum creatinine were monitored. Clinical baseline data and histological findings of two groups were compared. Results There were no significant differences in terms of age, gender, hypertension, hematuria, seralbumin, 24-hour proteinuria or serum creatinine between the two groups with various GFR before treatment （all P〉O. 05）. Neither were the incidences of balloon sclerosis, mesangial hyperplasia, crescent formation, interstitial sclerosis, tubular atrophy or vascular lesions （all P〈0.05）. Serum albumin was significantly increased and 24-hour proteinuria was significantly decreased in all IgAN patients at 3 months after treatment （P〈0.05）. There was no significant difference of the level of serum creatinine before and after treatment in the patients with eGFR〈70 mL min-1 1.73 m-2 in the steroid group. However, in the cyclophosphamide group, the level of serum creatinine at the final follow-up was significantly higher than the baseline level （all P〈O. 05）. The levels of serum creatinine before and after treatment were not significantly changed in patients with eGFR〉70 mL min-1 1.73 m-2 in either of the groups （all P〉0.05）. In steroid group, two patients had abnormal glucose tolerance, which was improved after steroid reduction; one patient suffered from liver damage and liver function became normal after treatment. In steroid plus cyclophosphamide group, one case had osteoporosis and 2 had abnormal glucose tolerance. No severe infections or other adverse reactions occurred in the patients of the two groups. Conclusion Both steroid therapy and cytotoxic medication can effectively reduce proteinuria in IgAN patients with impaired renal function. But there is no adequate evidence that cyclophosphamide is beneficial to the IgAN prognosis and can slow down renal function decline.
出处
《上海医学》
CAS
CSCD
北大核心
2012年第9期746-750,共5页
Shanghai Medical Journal
基金
国家自然科学基金青年项目资助(30600291)
