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王泳,张如霖,邱建新.含小剂量西罗莫司的四联免疫抑制方案治疗移植肾功能不全[J].Academic Journal of Second Military Medical University ,2021,42(9):1015-1020
含小剂量西罗莫司的四联免疫抑制方案治疗移植肾功能不全    点此下载全文 Fulltext
王泳1  张如霖2  邱建新1*
1. 上海交通大学附属第一人民医院泌尿外科, 上海 200080;
2. 上海交通大学附属第一人民医院检验科, 上海 200080
*通信作者
基金项目:上海交通大学STAR计划项目(20190102).
DOI:10.16781/j.0258-879x.2021.09.1015
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摘要:
      目的 观察以小剂量西罗莫司为主的四联免疫抑制方案对移植肾功能不全的治疗效果。方法 选择59例(男44例、女15例)接受三联免疫抑制剂(霉酚酸制剂/咪唑立宾+钙调磷酸酶抑制剂+糖皮质激素)治疗的移植肾功能不全患者,在减少钙调磷酸酶抑制剂剂量的同时加用小剂量西罗莫司(初始剂量0.5 mg/d,目标血药浓度为2~4 ng/mL),转换为四联免疫抑制剂方案治疗。记录西罗莫司和钙调磷酸酶抑制剂血药浓度的变化,分析药物转换前后血肌酐、血脂等指标的变化。结果 59例患者均完成四联免疫抑制剂治疗转换,至四联免疫抑制剂治疗调整完成时,西罗莫司血药浓度为(4.74±1.62)ng/mL;其中53例实现了钙调磷酸酶抑制剂血药浓度降低,降低比例为(37.00±19.00)%。调整治疗后,患者血肌酐水平降低[(111.53±24.87)μmol/L vs (148.88±27.64)μmol/L,P<0.01),甘油三酯水平[(1.93±1.08)mmol/L vs (1.89±0.77)mmol/L,P>0.05]和胆固醇水平[(5.30±1.39)mmol/L vs (4.96±1.19)mmol/L,P>0.05]变化不明显。将59例患者分为早期转换组(肾移植术后1~23个月转换四联免疫抑制剂治疗,n=44)和晚期转换组(术后32~159个月转换四联免疫抑制剂治疗,n=15),早期转换组肾功能恢复正常的患者比例高于晚期转换组[77.27%(34/44)vs 40.00%(6/15),P<0.05];早期转换组血肌酐水平较转换前降低[(106.41±19.78)μmol/L vs (151.43±28.68)μmol/L,P<0.05],晚期转换组血肌酐水平降低不明显[(126.53±32.18)μmol/L vs (141.40±24.76)μmol/L,P>0.05]。结论 减少钙调磷酸酶抑制剂的同时增加小剂量西罗莫司的四联免疫抑制方案可显著改善肾移植术后移植肾功能不全,且不会增加血脂异常不良反应,并且对于术后早期移植肾功能不全患者疗效更好。
关键词:移植肾功能不全  西罗莫司  钙调神经磷酸酶抑制剂  免疫抑制剂四联疗法
A small dose of sirolimus-based quadruple immunosuppressive regimen for the treatment of renal allograft dysfunction    Fulltext
WANG Yong1  ZHANG Ru-lin2  QIU Jian-xin1*
1. Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China;
2. Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
*Corresponding author
Fund Project:Supported by STAR Program of Shanghai Jiao Tong University (20190102).
Abstract:
      Objective To observe the therapeutic effect of a small dose of sirolimus-based quadruple immunosuppressive regimen for the treatment of renal allograft dysfunction. Methods Totally 59 patients (44 males and 15 females) with renal allograft dysfunction treated with triple immunosuppressants (mycophenolic acid/mizoribine+calcineurin inhibitors[CNIs]+glucocorticoids) were selected. While the dose of CNIs was reduced, a small dose of sirolimus (initial dose 0.5 mg/d, target blood concentration 2-4 ng/mL) was added so as to convert to the quadruple immunosuppressive regimen. The changes of the blood concentrations of sirolimus and CNIs were recorded, and the indexes of the serum creatinine and blood lipid were analyzed before and after conversion. Results All the 59 patients completed the conversion of quadruple therapy, and the blood concentration of sirolimus was (4.74±1.62) ng/mL; and the blood concentration of CNIs was decreased by (37.00±19.00)% in 53 cases. After adjustment of treatment, serum creatinine level was significantly decreased ([111.53±24.87] μmol/L vs[148.88±27.64] μmol/L, P<0.01). No significant changes were found for the triglyceride ([1.93±1.08] mmol/L vs[1.89±0.77] mmol/L, P>0.05) or cholesterol ([5.30±1.39] mmol/L vs[4.96±1.19] mmol/L, P>0.05). The 59 patients were divided into early conversion group (conversion to quadruple therapy within 1-23 months after renal transplantation, n=44) and late conversion group (conversion to quadruple therapy within 32-159 months after operation, n=15). The proportion of patients with normal renal function in the early conversion group was significantly higher than that in the late conversion group (77.27%[34/44] vs 40.00%[6/15], P<0.05); and the serum creatinine level in the early conversion group was significantly lower than that before conversion ([106.41±19.78] μmol/L vs[151.43±28.68] μmol/L, P<0.05), while no significant decrease was noticed in the late conversion group ([126.53±32.18] μmol/L vs[141.40±24.76] μmol/L, P>0.05). Conclusion Reducing CNIs, while adding a small dose of sirolimus, can significantly improve renal allograft dysfunction after renal transplantation, without increasing the adverse reactions of dyslipidemia. A small dose of sirolimus-based quadruple immunosuppressive therapy is more effective in patients with early postoperative renal allograft dysfunction.
Keywords:renal allograft dysfunction  sirolimus  calcineurin inhibitors  quadruple immunosuppressive therapy
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