激素联合他克莫司治疗糖尿病合并特发性膜性肾病的疗效观察

Clinical efficacy of tacrolimus combined with glucocorticoids in treatment of diabetes mellitus with idiopathic membranous nephropathy

目的观察2型糖尿病合并特发性膜性肾病(IMN)患者应用他克莫司联合小剂量激素治疗的疗效和安全性。方法回顾性纳入2012年6月—2017年6月经肾穿刺活检术确诊的糖尿病合并IMN的患者,应用激素联合他克莫司治疗者23例。给予起始剂量波尼松0.5mg/(kg·d)(或甲泼尼龙0.4mg/(kg·d))+他克莫司0.075 mg/(kg·d)治疗,观察治疗3、6、12个月时尿蛋白定量、白蛋白、血肌酐、肝功能、血脂血糖等变化,记录感染、心脑血管事件等不良反应的发生情况。结果激素联合他克莫司治疗3个月后尿蛋白定量开始显著减少(P<0.05),治疗6个月后血白蛋白开始显著上升(P<0.05)。治疗6个月肾病缓解率47.8%,12个月肾病缓解率65.2%。随访1年血糖进一步升高者69.6%(16/23)、感染率17.4%(4/23)、心脑血管并发症发生率8.7%(2/23)。结论激素联合免他克莫司是DM+IMN患者的有效治疗方案,临床缓解率高,但可能增加糖尿病患者血糖升高、感染及心脑血管事件发生风险。

Objective To investigate the efficacy and safety of tacrolimus combined with low-dose corticosteroids therapy in patients with type 2 diabetes mellitus（ DM） occurring with idiopathic membranous nephropathy（ IMN）.Methods Totall 23 patients who were disgnosed with DM occurring with IMN by renal biopsy were included retrospectively,all of them were treated with corticosteroids combined with tacrolimus. A initial dose of prednisone 0. 5 mg/kg/day（ or methylprednisolone 0. 5 mg/kg/day） and tacrolimus 0. 05-0. 075 mg/kg/d was given to those patients. The urinary protein,albumin,serum creatinine,liver function,and blood lipid and blood glucose were observed for 3 months,6 months,12 months under their therapy. The occurrence of adverse reactions such as infection and cardiovascular and cerebrovascular events were recorded. Results The treatment of tacrolimus combined with glucocorticoids significantly reduced the urinary protein after 3 months（ P 〈 0. 05）,earlier than albumin rising,then the serum albumin began to increase significantly after 6 months of treatment（ P 〈 0. 05）. 47. 8% of the patients achieved remission in the sixth mounth,and the remission rate was 65. 2% in the twelveth mounth. During the treatment,69. 6%（ 16/23） of the patients suffer worse blood glucose and the infection rate was 17. 4%（ 4/23）. The incidence rate of cardiovascular and cerebrovascular complications was 8. 7%（ 2/23）. Conclusion The therapy of corticosteroids combined with tacrolimus is effective for patients with DM occurring with IMN. The clinical remission rate is high,but it may increase the risk of hyperglycemia,infection,and cardiovascular and cerebrovascular events in diabetic.