钠-葡萄糖协同转运蛋白2抑制剂治疗原发性膜性肾病的疗效及其对Th1/Th2的影响

Efficacy of sodium-glucose cotransporter 2 inhibitor therapy for idiopathic membranous nephropathy and its effect on Th1/Th2 ratio

目的探讨钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)治疗原发性膜性肾病的疗效及其对Th1/Th2的影响。方法采用单中心随机对照研究,选取2022年1月至2023年12月在贵阳市第一人民医院肾穿刺活检或经抗磷脂酶A2受体抗体检测确诊原发性膜性肾病的初治患者48例。随机分为两组:血管紧张素Ⅱ受体阻滞剂(ARB)联合SGLT2i组(治疗组,口服厄贝沙坦300 mg/d和达格列净10 mg/d)、ARB组(对照组,口服厄贝沙坦300 mg/d),每组24例。收集患者的基本信息,以及肾功能、血脂、血糖、T淋巴细胞亚群Th1和Th2等实验室指标基线数值,并于治疗4周、8周、12周时复查,比较分析SGLT2i的疗效及其对Th1/Th2的影响。结果治疗组原发性膜性肾病患者的临床疗效总有效率高于对照组(95.93%比70.83%,P<0.05)。治疗组患者治疗4周、8周、12周时的24 h尿蛋白水平均低于对照组[(2081.24±977.51)mg比(2577.25±1286.44)mg,(1776.50±676.24)mg比(2163.25±620.44)mg,(812.44±383.25)mg比(1681.21±477.58)mg,P均<0.001]。治疗组患者治疗8周、12周时的血清白蛋白水平亦均高于对照组[(37.53±3.87)g/L比(32.52±3.69)g/L、(38.12±4.13)g/L比(33.26±4.01)g/L,P均<0.001],而治疗组患者治疗12周的总胆固醇水平低于对照组[(5.12±0.84)mmol/L比(6.41±0.62)mmol/L,P<0.001];治疗组患者治疗8周、12周的甘油三酯亦均低于对照组[(1.62±0.81)mmol/L比(2.01±0.53)mmol/L、(1.50±0.91)mmol/L比(1.99±0.74)mmol/L,P均<0.001]。此外,治疗组患者治疗12周时的Th1/Th2比值高于对照组[(1.01±0.31)比(0.38±0.19),P<0.001]。结论SGLT2i可以降低原发性膜性肾病患者的蛋白尿水平,改善血脂代谢,提高Th1/Th2比值。

Objective To investigate the efficacy of sodium-glucose cotransporter 2 inhibitor(SGLT2i)for idiopathic membranous nephropathy and its effect on Th1/Th2 ratio.Method A singlecenter randomized controlled study was conducted by selecting 48 patients with idiopathic membranmembranic nephropathy who were diagnosed by renal biopsy or anti-phospholipase A2 receptor antibody detection and received initial formal treatment in Guiyang First People&apos;s Hospital from January 2022 to December 2023.The patients were randomly divided into two groups,a group of angiotensin II receptor blocker(ARB)combined with SGLT2i(treatment group,oral irbesartan 300 mg/d and dagliprazin 10 mg/d),and an ARB group(control group,oral irbesartan only 300 mg/d)with 24 patients in each.Demographic data,indicators of blood lipid,blood glucose,renal function,as well as T lymphocyte subsets Th1/Th2 ratio were collected,which was re-examined at 4 weeks,8 weeks,and 12 weeks after the treatment.The efficacy of therapy and its effect on Th1/Th2 ratio in the two groups were compared.Results The total effective rate of the treatment group was higher than that of the control group(95.93%vs 70.83%,P<0.05).After treating for 4 weeks,8 weeks,and 12 weeks,the treatment group showed lower levels of 24h urinary protein than the control group[(2081.24±977.51)mg vs(2577.25±1286.44)mg,(1776.50±676.24)mg vs.(2163.25±620.44)mg,(812.44±383.25)mg vs(1681.21±477.58)mg,P<0.001].Compared with the control group,the treatment group showed higher levels of serum albumin[(37.53±3.87)g/L vs(32.52±3.69)g/L,(38.12±4.13)g/L vs(33.26±4.01)g/L,P<0.001]after treating for 8 weeks and 12 weeks,lower level of total cholesterol after treating for 12 weeks[(5.12±0.84)mmol/L vs(6.41±0.62)mmol/L,P<0.001],and also lower levels of triglycerides after treating for 8 weeks and 12 weeks[(1.62±0.81)mmol/L vs(2.01±0.53)mmol/L,and(1.50±0.91)mmol/L vs(1.99±0.74)mmol/L,P<0.001].Besides,the Th1/Th2 ratio in the treatment group was higher than that in the control group after treating for 12 weeks[(1.01±0.31)vs(0.38±0.19),P<0.001].Conclusion SGLT2i could reduce proteinuria,improve lipid metabolism,and increase Th1/Th2 ratio in the patients with idiopathic membranous nephropathy.