阿法骨化醇对高血压肾损害患者肝肾功能、炎症因子及RAS活性的影响

Efficacy of alfacalcidol on liver and kidney function,inflammatory cytokines and RAS activity in hypertensive patients with renal impairment

目的探讨阿法骨化醇联合常规降压降脂药对高血压肾损害患者肝肾功能、血清炎症因子与肾素-血管紧张素系统(RAS)活性的影响。方法选择2017年12月-2020年12月在我院肾内科就诊的高血压肾损害患者200例,按随机数表法分为对照组和观察组,每组100例。2组患者均给予常规降压降脂治疗(共14周),观察组患者在治疗2周后联合给予口服阿法骨化醇治疗(每次0.25μg,每日1次,共12周)。观察2组患者治疗前后的肝功能指标[天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)]、肾功能指标[血钙、血磷、尿素氮(BUN)、胱抑素C(Cys-C)、血清肌酐(Scr)、尿微量白蛋白(mAlb)、β_(2)微球蛋白(β_(2)-MG)、尿N-乙酰β-D-氨基葡萄糖苷酶(NAG)、24 h尿蛋白水平]、炎症因子[血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、高敏C-反应蛋白(hs-CRP)]水平、RAS活性指标[血清肾素、血管紧张素Ⅰ(AngⅠ)、AngⅡ、醛固酮]水平,并记录治疗期间不良反应发生情况。结果2组患者在治疗前的各项检测指标水平比较,差异均无统计学意义(P>0.05)。治疗后,观察组患者的血钙水平较治疗前显著升高(P<0.05),但仍维持在临床正常水平;观察组患者的Cys-C、Scr、BUN、尿mAlb、β_(2)-MG、NAG、24 h尿蛋白水平、hs-CRP、IL-6、TNF-α、血清肾素、AngⅠ、AngⅡ和醛固酮水平较治疗前显著下降(P<0.05)。治疗后,观察组患者的血钙水平显著高于对照组(P<0.05);而Cys-C、Scr、BUN、尿m Alb、β_(2)-MG、NAG、24 h尿蛋白水平、hs-CRP、IL-6、TNF-α、血清肾素、AngⅠ、AngⅡ和醛固酮水平显著低于对照组(P<0.05)。2组患者用药期间不良反应发生率比较,差异无统计学意义(P>0.05)。结论在常规降压降脂药基础上联用阿法骨化醇能有效改善高血压肾损害患者肝肾功能,抑制其炎症反应和RAS活性,且安全性良好。

OBJECTIVE To explore the efficacy of alfacalcidol combined with conventional antihypertensive and lipid-lowering drugs on liver and kidney function,serum inflammatory cytokines and renin-angiotensin system(RAS)in hypertensive patients with renal impairment.METHODS A total of 200 hypertensive patients with renal impairment who were treated in the department of nephrology in our hospital from December 2017 to December 2020 were selected and randomly divided into control group and observation group,with 100 cases in each group.Both groups of patients were treated with conventional antihypertensive and lipid-lowering drugs for a total of 14 weeks,patients in the observation group were additionally treated with oral alfacalcidol after 2 weeks of treatment(0.25μg each time,once a day,for a total of 12 weeks).The levels of liver function indexes[aspartate aminotransferase(AST),alanine aminotransferase(ALT)],renal function indexes[blood calcium,blood phosphorus,blood urea nitrogen(BUN),cystatin C(Cys-C),serum creatinine(Scr),urine microalbumin(mAlb),β_(2)-microglobulin(β_(2)-MG),urinary N-acetylβ-D-glucosaminidase(NAG),24 h urinary protein],inflammatory factors[serum interleukin 6(IL-6),tumor necrosis factorα(TNF-α),hypersensitive C-reactive protein(hs-CRP)]and RAS activity indexes[renin,angiotensinⅠ(AngⅠ),AngⅡand aldosterone]were observed in 2 groups before and after treatment,and the occurrence of adverse drug reactions was recorded during treatment.RESULTS There was no statistical significance in the levels of detection indexes between 2 groups before treatment(P>0.05).After treatment,the level of blood calcium in the observation group was significantly higher than before treatment(P<0.05),but remained at clinically normal level.Compared with before treatment,the levels of Cys-C,Scr,BUN,urine mAlb,β_(2)-MG,NAG and 24 h urinary protein,hs-CRP,IL-6,TNF-α,renin,AngⅠ,AngⅡand aldosterone were significantly decreased in the observation group after treatment(P<0.05).After treatment,the level of blood calcium in observation group was significantly higher than control group(P<0.05).Additionally,the levels of Cys-C,Scr,BUN,urine mAlb,β_(2)-MG,NAG,24 h urinary protein,hs-CRP,IL-6,TNF-α,renin,AngⅠ,AngⅡand aldosterone were significantly lower than control group(P<0.05).There was no statistical significance in the incidence of adverse drug reactions between 2 groups during treatment(P>0.05).CONCLUSIONS Alfacalcidol combined with routine therapy of antihypertensive and lipid-lowering drugs could effectively improve liver and renal functions,inhibit inflammation and RAS activity in hypertensive patients with renal impairment,with a favorable safety.