他克莫司联合糖皮质激素对难治性肾病综合征患者肝肾功能、糖脂代谢及不良反应的影响
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摘要
目的观察他克莫司(FK506)联合糖皮质激素(GC)治疗对难治性肾病综合征(RNS)患者的肝肾功能、糖脂代谢和不良反应的影响。方法选取2015年9月—2017年9月仙桃市第一人民医院RNS患者66例,按治疗方法分为观察组和对照组,每组33例,对照组采用环磷酰胺+GC;观察组采用FK506+GC。于治疗前及治疗6个月后检测2组肝、肾功能、糖脂代谢及尿肾损伤标志物水平,观察并记录药物不良反应情况。结果 2组治疗前、治疗6个月后丙氨酸氨基转移酶、天冬门氨酸转移酶、空腹血糖组间及组内比较差异均无统计学意义(P> 0. 05)。2组治疗后24 h尿蛋白定量、肌酐、尿素氮、甘油三酯、胆固醇均低于治疗前,且观察组低于对照组(P <0. 05)。2组治疗后尿视黄醇结合蛋白、肾损伤分子-1、N-乙酰-β-D葡萄糖酐酶水平均低于治疗前,且观察组低于对照组(P <0. 05)。2组不良反应发生率比较差异无统计学意义(P> 0. 05)。结论 FK506联合GC治疗RNS可改善患者肾功能和血脂代谢状态,减轻肾损伤,对肝功能无显著影响,不良反应少,有利于控制疾病进展、促进患者恢复。
Objective To observe effects of Tacrolimus( FK506) combined with glucocorticoids( GC) on liver and kidney function,glucolipid metabolism and adverse reactions in patients with refractory nephrotic syndrome( RNS).Methods A total of 66 RNS patients admitted during September 2015 and September 2017 were divided into observation group and control group( n = 33 for each group) according to therapeutic methods. Control group was treated with Cyclophosphamide + GC,while observation group was treated with FK506 + GC. In two groups,levels of liver function,renal function indexes,glucolipid metabolism and urinary and renal injury markers were detected before and after treatment for 6 months,and conditions of adverse drug reactions were observed. Results There were no significant differences in levels of alanine aminotransferase,aspartate aminotransferase and fasting blood glucose before and after treatment for 6months between two groups( P > 0. 05). After treatment,levels of 24 h urinary protein quantitation,creatinine,urea nitrogen,triglyceride and cholesterol were significantly lower than those before treatment in two groups,and the levels in observation group were significantly lower than those in control group( P < 0. 05); levels of urinary retinol binding protein,renal injury molecule-1 and N-acetyl-β-D glucuronidase were lower than those before treatment in two groups,and the levels in observation group were significantly lower than those in control group( P < 0. 05). There was no significant difference in incidence rate of adverse reactions between two groups( P > 0. 05). Conclusion Tacrolimus combined with GC in treatment of patients with refractory nephrotic syndrome may improve renal function and blood lipid metabolism and reduce renal injury,and it has no significant effect on liver function with few adverse reactions,and therefore it is helpful to control progression of disease and promote recovery of patients.
Objective To observe effects of Tacrolimus( FK506) combined with glucocorticoids( GC) on liver and kidney function,glucolipid metabolism and adverse reactions in patients with refractory nephrotic syndrome( RNS).Methods A total of 66 RNS patients admitted during September 2015 and September 2017 were divided into observation group and control group( n = 33 for each group) according to therapeutic methods. Control group was treated with Cyclophosphamide + GC,while observation group was treated with FK506 + GC. In two groups,levels of liver function,renal function indexes,glucolipid metabolism and urinary and renal injury markers were detected before and after treatment for 6 months,and conditions of adverse drug reactions were observed. Results There were no significant differences in levels of alanine aminotransferase,aspartate aminotransferase and fasting blood glucose before and after treatment for 6months between two groups( P > 0. 05). After treatment,levels of 24 h urinary protein quantitation,creatinine,urea nitrogen,triglyceride and cholesterol were significantly lower than those before treatment in two groups,and the levels in observation group were significantly lower than those in control group( P < 0. 05); levels of urinary retinol binding protein,renal injury molecule-1 and N-acetyl-β-D glucuronidase were lower than those before treatment in two groups,and the levels in observation group were significantly lower than those in control group( P < 0. 05). There was no significant difference in incidence rate of adverse reactions between two groups( P > 0. 05). Conclusion Tacrolimus combined with GC in treatment of patients with refractory nephrotic syndrome may improve renal function and blood lipid metabolism and reduce renal injury,and it has no significant effect on liver function with few adverse reactions,and therefore it is helpful to control progression of disease and promote recovery of patients.
引文
[1]姜维.泼尼松联合吗替麦考酚酯治疗对难治性肾病综合征患者细胞免疫功能及细胞因子的影响[J].中国医师杂志,2017,19(5):742-744.
[2]张颖.吗替麦考酚酯与环磷酰胺联合激素治疗成人难治性肾病综合征的疗效和安全性比较[J].现代中西医结合杂志,2017,26(6):596-598,602.
[3]李永珍,何庆南.原发性肾病综合征免疫发病机制研究进展[J].国际儿科学杂志,2016,43(1):51-55.
[4]周丽华,陈勋.多靶点治疗老年难治性肾病综合征的临床分析[J].山西医药杂志,2017,46(6):702-703.
[5]邓时素,欧三桃.甲泼尼龙联合他克莫司治疗老年原发性肾病综合征的临床观察[J].中国药房,2016,27(32):4528-4531.
[6]中国成人肾病综合征免疫抑制治疗专家组.中国成人肾病综合征免疫抑制治疗专家共识[J].中华肾脏病杂志,2014,30(6):467-474.
[7]史添立,罗贞,焦石,等.强化免疫抑制方案治疗难治性肾病综合征的临床观察[J].中国药房,2017,28(23):3237-3240.
[8]李小会,雷根平,潘冬辉.难治性肾病综合征的中西医研究进展[J].中国中西医结合肾病杂志,2013,14(1):87-89.
[9]郝静,袁伟杰.难治性肾病综合征的病因及治疗研究进展[J].中国中西医结合肾病杂志,2013,14(6):553-555.
[10]周福德.原发性肾病综合征的免疫抑制治疗进展[J].临床药物治疗杂志,2015,13(1):5-8.
[11]黄宇新,赵雄,胡仕畅,等.肾病综合征中西医结合治疗进展[J].辽宁中医药大学学报,2015,17(2):219-221.
[12]沈辛宜,高继宁.中药联合激素治疗肾病综合征临床研究[J].山西医药杂志,2016,45(1):69-70.
[13]梁玉梅,陈愔音,龚钰婷,等.糖皮质激素受体及免疫炎症介质在肾病综合征复发机制中的作用及研究进展[J].医学临床研究,2013,30(1):156-158.
[14]李小红,王函,李康慧.不同激素量联合环磷酰胺及雷公藤治疗中老年肾病综合征的疗效[J].中国老年学,2017,37(1):167-169.
[15]陈咏琦,朱艳,郝胜,等.急性肾损伤标志物在钙调神经蛋白抑制剂治疗难治性肾病综合征中的意义[J].中华实用儿科临床杂志,2017,32(17):1300-1304.
[16]林丽娟,陈兴强,吴琳虹,等.环孢素A与环磷酰胺联合激素治疗难治性肾病综合征的疗效比较[J].河北医科大学学报,2015,36(3):320-322.
[17]高丹,吴歌.他克莫司和来氟米特治疗难治性肾病综合征的疗效比较[J].现代药物与临床,2017,32(4):675-677.
[18]宋艳,成璐,贾淼鑫,等.肾病综合征患者他克莫司血药浓度监测的回顾性分析与评价[J].中国医院药学杂志,2017,37(7):654-658.
[19]童科珍,毛建华,吴波英,等.他克莫司和吗替麦考酚酯分别联合激素治疗肾病综合征患儿疗效比较[J].中华全科医学,2017,15(8):1337-1339.
[20]王曙,赖柳生,眭维国,等.肾移植术后CYP3A5基因多态性对他克莫司血药浓度的影响[J].解放军医药杂志,2015,27(8):9-11.
[21]张月丽,明英姿,周宏灏,等.他克莫司:药代动力学,药效动力学和药物基因组学[J].中国临床药理学与治疗学,2014,19(9):1042-1050.
[22]陈菊,周君,朱永俊.他克莫司与环磷酰胺治疗更年期狼疮性肾炎的效果及安全性比较[J].解放军医药杂志,2017,29(8):90-92.
[23]陈波,邱敏,荣冬靖.他克莫司联合糖皮质激素治疗成人难治性肾病综合征的临床效果评估[J].中国医学前沿杂志:电子版,2016,8(11):68-71.
[2]张颖.吗替麦考酚酯与环磷酰胺联合激素治疗成人难治性肾病综合征的疗效和安全性比较[J].现代中西医结合杂志,2017,26(6):596-598,602.
[3]李永珍,何庆南.原发性肾病综合征免疫发病机制研究进展[J].国际儿科学杂志,2016,43(1):51-55.
[4]周丽华,陈勋.多靶点治疗老年难治性肾病综合征的临床分析[J].山西医药杂志,2017,46(6):702-703.
[5]邓时素,欧三桃.甲泼尼龙联合他克莫司治疗老年原发性肾病综合征的临床观察[J].中国药房,2016,27(32):4528-4531.
[6]中国成人肾病综合征免疫抑制治疗专家组.中国成人肾病综合征免疫抑制治疗专家共识[J].中华肾脏病杂志,2014,30(6):467-474.
[7]史添立,罗贞,焦石,等.强化免疫抑制方案治疗难治性肾病综合征的临床观察[J].中国药房,2017,28(23):3237-3240.
[8]李小会,雷根平,潘冬辉.难治性肾病综合征的中西医研究进展[J].中国中西医结合肾病杂志,2013,14(1):87-89.
[9]郝静,袁伟杰.难治性肾病综合征的病因及治疗研究进展[J].中国中西医结合肾病杂志,2013,14(6):553-555.
[10]周福德.原发性肾病综合征的免疫抑制治疗进展[J].临床药物治疗杂志,2015,13(1):5-8.
[11]黄宇新,赵雄,胡仕畅,等.肾病综合征中西医结合治疗进展[J].辽宁中医药大学学报,2015,17(2):219-221.
[12]沈辛宜,高继宁.中药联合激素治疗肾病综合征临床研究[J].山西医药杂志,2016,45(1):69-70.
[13]梁玉梅,陈愔音,龚钰婷,等.糖皮质激素受体及免疫炎症介质在肾病综合征复发机制中的作用及研究进展[J].医学临床研究,2013,30(1):156-158.
[14]李小红,王函,李康慧.不同激素量联合环磷酰胺及雷公藤治疗中老年肾病综合征的疗效[J].中国老年学,2017,37(1):167-169.
[15]陈咏琦,朱艳,郝胜,等.急性肾损伤标志物在钙调神经蛋白抑制剂治疗难治性肾病综合征中的意义[J].中华实用儿科临床杂志,2017,32(17):1300-1304.
[16]林丽娟,陈兴强,吴琳虹,等.环孢素A与环磷酰胺联合激素治疗难治性肾病综合征的疗效比较[J].河北医科大学学报,2015,36(3):320-322.
[17]高丹,吴歌.他克莫司和来氟米特治疗难治性肾病综合征的疗效比较[J].现代药物与临床,2017,32(4):675-677.
[18]宋艳,成璐,贾淼鑫,等.肾病综合征患者他克莫司血药浓度监测的回顾性分析与评价[J].中国医院药学杂志,2017,37(7):654-658.
[19]童科珍,毛建华,吴波英,等.他克莫司和吗替麦考酚酯分别联合激素治疗肾病综合征患儿疗效比较[J].中华全科医学,2017,15(8):1337-1339.
[20]王曙,赖柳生,眭维国,等.肾移植术后CYP3A5基因多态性对他克莫司血药浓度的影响[J].解放军医药杂志,2015,27(8):9-11.
[21]张月丽,明英姿,周宏灏,等.他克莫司:药代动力学,药效动力学和药物基因组学[J].中国临床药理学与治疗学,2014,19(9):1042-1050.
[22]陈菊,周君,朱永俊.他克莫司与环磷酰胺治疗更年期狼疮性肾炎的效果及安全性比较[J].解放军医药杂志,2017,29(8):90-92.
[23]陈波,邱敏,荣冬靖.他克莫司联合糖皮质激素治疗成人难治性肾病综合征的临床效果评估[J].中国医学前沿杂志:电子版,2016,8(11):68-71.