摘要
目的评估非布司他降尿酸治疗对慢性肾脏病(CKD)3~5期伴高尿酸血症(HUA)患者氧化应激反应的影响。方法本研究为前瞻性队列研究。入选2015年6月至2018年6月于青岛大学附属医院肾内科门诊或住院的CKD 3~5期非透析患者为研究对象。根据血尿酸水平及降尿酸药物的不同,分为非布司他(A)组、别嘌呤醇(B)组和非高尿酸血症(C)组,检测各组患者基线及治疗后1个月、3个月的血尿酸、超敏C反应蛋白(hs-CRP)、丙二醛(MDA)、超氧化物歧化酶(SOD)以及内皮素-1(ET-1)等指标,比较各组降尿酸治疗前后血尿酸、炎性反应及氧化应激指标的变化。根据血尿酸是否达标,分别将基线和治疗3个月后患者分为尿酸达标组和尿酸未达标组,采用Spearman相关性分析血尿酸与炎性反应及氧化应激指标的相关性。结果A组与B组基线血尿酸、炎性反应及氧化应激等指标的差异无统计学意义(均P>0.05),A组和B组基线血尿酸和hs-CRP、MDA、ET-1水平显著高于C组,基线SOD水平显著低于C组,差异有统计学意义(均P<0.001)。治疗1个月和3个月后,A组血尿酸、hs-CRP、MDA和ET-1水平显著低于B组,SOD水平明显高于B组,两组间比较差异有统计学意义(P<0.001)。与基线值相比,治疗3个月后A组和B组血尿酸、hs-CRP、MDA和ET-1水平显著下降,A组下降幅度显著高于B组;SOD水平显著升高,A组比B组升高幅度更大,组间比较差异有统计学意义(均P<0.001)。在基线和治疗3个月后,未达标组血尿酸与hs-CRP、MDA和ET-1均呈正相关,与SOD呈负相关(| r|均大于0.50,P<0.001);达标组血尿酸与hs-CRP、MDA和SOD均呈正相关(| r|均大于0.70,P<0.001),尿酸与ET-1无相关性(P>0.05)。结论与别嘌呤醇相比,非布司他能更有效地降低尿酸并抑制CKD 3~5期伴高尿酸血症患者氧化应激反应,减少血管内皮损伤。血尿酸升高可能是促进CKD患者氧化应激反应和增加内皮损伤的重要因素之一。
Objective To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease (CKD) stages 3-5 patients with hyperuricemia (HUA). Methods The study was a prospective cohort study. The patients of CKD stages 3-5 with HUA between June 2015 and June 2018 in the Affiliated Hospital of Qingdao University were prospectively analyzed. The patients were assigned to febuxostat (A) group, allopurinol (B) group and non-hyperuricemia (C) group according to the level of serum uric acid and the choice of urate-lowering drugs. Serum uric acid, hypersensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA), superoxide dismutase (SOD) and endothelin-1 (ET-1) were measured at baseline, 1 month and 3 months after treatment and the changes of the values of inflammation and oxidative stress before or after treatment were compared. According to the level of serum uric acid, patients were divided into attainment group and nonattainment group, and the correlation between uric acid and oxidative stress was analyzed at baseline and 3 months after treatment respectively. Results There was no significant difference in baseline levels of serum uric acid, inflammation and oxidative stress between group A and group B (P>0.05). The levels of serum uric acid, hs-CRP, MDA and ET-1 of group A and group B were significantly higher than those of group C, but the level of SOD of group A and group B was significantly lower than that of group C at baseline (P<0.001). After treatment for 1 month and 3 months, the values of serum uric acid, hs-CRP, MDA and ET-1 in group A were significantly lower than those in group B, while the level of SOD in group A was significantly higher than that in group B (P<0.001). Compared with pre-treatment period, both the serum uric acid, hs-CRP, MDA and ET-1 levels of group A and group B were declined significantly while SOD had a significant rise after 3 months treatment (P<0.001). The changes of group A were significantly higher than those of group B (P<0.001). At baseline and 3 months after treatment, serum uric acid was positively related to hs-CRP, MDA and ET-1, but negatively related to SOD in nonattainment group (| r|>0.50, P<0.001);serum uric acid was positively related to hs-CRP, MDA and SOD (| r|>0.70, P<0.001), and there was no correlation between serum uric acid and ET-1 in attainment group (P>0.05). Conclusions Febuxostat performed better than allopurinol in lowering urate and inhibiting oxidative stress in CKD stages 3-5 patients with HUA, thus reducing vascular endothelial injury. Elevated serum uric acid may be one of the important factors that promote oxidative stress and increase endothelial damage in CKD patients.
作者
张小筱
车琳
张慧
王雁飞
王玲
郭丹丹
刘雪梅
Zhang Xiaoxiao;Che Lin;Zhang Hui;Wang Yanfei;Wang Ling;Guo Dandan;Liu Xuemei(Department of Nephrology,Affiliated Hospital of Qingdao University,Qingdao 266003,China)
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2019年第9期676-683,共8页
Chinese Journal of Nephrology
基金
青岛大学医学部"临床医学+X"工程科研项目(2018-21).
