他克莫司联合糖皮质激素治疗特发性膜性肾病的疗效及对肾功能损害相关指标水平的影响

Clinical effects of tacrolimus combined with glucocorticoids in the treatment of idiopathic membranous nephropathy and its effect on the levels of renal function damage related indicators

目的观察他克莫司联合糖皮质激素治疗特发性膜性肾病(IMN)的疗效及对肾功能损害相关指标水平的影响。方法前瞻性选取2019年10月至2023年3月解放军联勤保障部队第九〇八医院收治的112例IMN患者为研究对象,按照简单随机法将其分为对照组和观察组,每组各56例。对照组给予环磷酰胺联合糖皮质激素治疗,观察组给予他克莫司联合糖皮质激素治疗。两组均持续治疗6个月。统计两组的疗效,比较两组治疗前、治疗6个月后肾功能[24 h尿蛋白定量(24 h UTP)、血肌酐、肾小球滤过率(GFR)]、肾功能损害相关指标[抗M型磷脂酶A2受体(PLA2R)抗体、肾损伤分子-1(Kim-1)、尿免疫球蛋白4(IgG4)、尿单核细胞趋化蛋白1(MCP-1)]、血脂代谢指标[总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)]及营养指标(血白蛋白、总蛋白)的差异,观察两组不良反应发生情况。结果观察组总有效率为92.86%,高于对照组(78.57%),差异有统计学意义(P<0.05)。治疗6个月后,两组24 h UTP、血肌酐均较治疗前降低,GFR均较治疗前升高,观察组24 h UTP、血肌酐分别为(1.34±0.42)g、(69.16±6.44)μmol/L,均低于对照组[(2.82±0.61)g、(76.85±7.05)μmol/L],GFR为(88.87±8.05)mL/(min·1.73m 2),高于对照组[(79.98±7.41)mL/(min·1.73m 2)],差异均有统计学意义(P<0.05)。治疗6个月后,两组PLA2R抗体、Kim-1、尿IgG4、尿MCP-1水平均较治疗前降低,观察组PLA2R抗体、Kim-1、尿IgG4、尿MCP-1水平分别为(3.23±0.69)μg/mL、(3.51±0.62)ng/mL、(2.51±0.63)g/L、(0.15±0.02)ng/mL,均低于对照组[(4.85±1.03)μg/mL、(4.76±0.86)ng/mL、(6.45±0.87)g/L、(0.29±0.06)ng/mL],差异均有统计学意义(P<0.05)。治疗6个月后,两组总胆固醇、甘油三酯、LDL-C水平均较治疗前降低,观察组的总胆固醇、甘油三酯、LDL-C水平分别为(3.85±0.59)、(1.87±0.36)、(3.27±0.43)mmol/L,均低于对照组[(5.17±0.65)、(3.28±0.43)、(3.88±0.54)mmol/L],差异均有统计学意义(P<0.05)。治疗6个月后,两组血白蛋白、总蛋白均较治疗前升高,观察组血白蛋白、总蛋白水平分别为(32.14±4.83)、(61.15±6.08)g/L,均高于对照组[(26.85±4.14)、(52.74±5.64)g/L],差异均有统计学意义(P<0.05)。治疗期间,两组均未发生严重不良反应。结论他克莫司联合糖皮质激素治疗IMN可提高患者疗效,改善肾功能,降低肾功能损害相关指标水平,调节脂代谢,改善营养指标,值得临床推广应用。

Objective To observe the efficacy of tacrolimus combined with glucocorticoid in the treatment of idiopathic membranous nephropathy(IMN)and its effect on the levels of renal function damage related indicators.Methods A total of 112 patients with IMN admitted to 908th Hospital of PLA Joint Logistic Support Force from October 2019 to March 2023 were prospectively selected as the research objects and divided into the control group and the observation group according to the simple random method,with 56 cases in each group.The control group was treated with cyclophosphamide combined with glucocorticoid,and the observation group was treated with tacrolimus combined with glucocorticoid.Both groups were treated for 6 months.The efficacy of the two groups was statistically analyzed.The renal function[24 h urinary protein quantification(24 h UTP),serum creatinine,glomerular filtration rate(GFR)],renal impairment related indicators[anti-M-type phospholipase A2 receptor(PLA2R)antibody,kidney injury molecule-1(Kim-1),urinary immunoglobulin 4(IgG4),urinary monocyte chemoattractant protein 1(MCP-1)],blood lipid metabolism indicators[total cholesterol,triglyceride,low-density lipoprotein cholesterol(LDL-C)]and nutritional indicators(serum albumin,total protein)were compared between the two groups before treatment and 6 months after treatment.The adverse reactions of the two groups were observed.Results The total effective rate of the observation group was 92.86%,which was higher than that of the control group(78.57%),and the difference was statistically significant(P<0.05).After 6 months of treatment,24 h UTP and serum creatinine in the two groups were lower than those before treatment,and GFR was higher than that before treatment,the 24 h UTP and serum creatinine in the observation group were(1.34±0.42)g and(69.16±6.44)μmol/L,respectively,which were lower than those in the control group[(2.82±0.61)g,(76.85±7.05)μmol/L],and GFR was(88.87±8.05)mL/(min·1.73 m 2),which was higher than that of the control group[(79.98±7.41)mL/(min·1.73 m 2)],and the difference was statistically significant(P<0.05).After 6 months of treatment,the levels of PLA2R antibody,Kim-1,urinary IgG4 and urinary MCP-1 in the two groups were lower than those before treatment,the levels of PLA2R antibody,Kim-1,urinary IgG4 and urinary MCP-1 in the observation group were(3.23±0.69)μg/mL,(3.51±0.62)ng/mL,(2.51±0.63)g/L and(0.15±0.02)ng/mL,respectively,which were lower than those in the control group[(4.85±1.03)μg/mL,(4.76±0.86)ng/mL,(6.45±0.87)g/L,(0.29±0.06)ng/mL],the differences were statistically significant(P<0.05).After 6 months of treatment,the levels of total cholesterol,triglyceride and LDL-C in the two groups were lower than those before treatment,the levels of total cholesterol,triglyceride and LDL-C in the observation group were(3.85±0.59),(1.87±0.36)and(3.27±0.43)mmol/L,respectively,which were lower than those in the control group[(5.17±0.65),(3.28±0.43)and(3.88±0.54)mmol/L],the differences were statistically significant(P<0.05).After 6 months of treatment,the serum albumin and total protein of the two groups were higher than those before treatment,the serum albumin and total protein of the observation group were(32.14±4.83)and(61.15±6.08)g/L,respectively,which were higher than those of the control group[(26.85±4.14)and(52.74±5.64)g/L],the differences were statistically significant(P<0.05).No serious adverse reactions occurred in both groups during the treatment.Conclusion Tacrolimus combined with glucocorticoid in the treatment of IMN can improve the efficacy of patients,improve renal function,reduce the level of renal function damage related indicators,regulate lipid metabolism,and improve nutritional indicators,which is worthy of clinical application.