不同剂量非布司他联合贝前列素钠对慢性肾病伴高尿酸血症患者肾功能及氧化应激的影响

Effects of different doses of febuxostat combined with beraprost sodium on renal function and oxidative stress in patients with chronic kidney disease accompanied by hyperuricemia

目的探讨不同剂量非布司他联合贝前列素钠对慢性肾脏病(CKD)伴高尿酸血症(HUA)患者肾功能及氧化应激的影响。方法CKD伴HUA患者225例,随机均分为高剂量组(非布司他80 mg/d)、中剂量组(非布司他40 mg/d)和低剂量组(非布司他20 mg/d),同时所有患者均给予联合贝前列素钠治疗;于治疗前和治疗后12周时采集空腹静脉血测定血肌酐(Ser)、血尿素氮(BUN)、超氧化物歧化酶(SOD)及丙二醛(MDA),同时留取晨尿检测24 h尿蛋白定量,并于治疗后4周、8周、12周时检测各组患者血尿酸达标率及治疗期间的不良反应发生率。结果治疗12周,3组Ser、BUN、24 h尿蛋白定量较治疗前下降,且高剂量组低于中剂量组和低剂量组,而中剂量组低于低剂量组,差异有统计学意义(P<0.05);治疗12周,3组患者SOD较治疗前升高,MDA较治疗前下降、且高剂量组SOD高于中剂量组和低剂量组、MDA低于中剂量组和低剂量组,而中剂量组SOD高于低剂量组,MDA低于低剂量组,差异有统计学意义(P<0.05);高剂量组治疗4周、8周、12周时血尿酸达标率高于中剂量组与低剂量组(P<0.05);高剂量组不良反应总发生率高于中剂量组和低剂量组,差异有统计学意义(P<0.05);中剂量组的不良反应发生率与低剂量组比较,差异无统计学意义(P>0.05)。结论80 mg/d非布司他联合贝前列素钠治疗CKD伴HUA患者,对患者肾功能和氧化应激指标具有较好的效果。

Objective To investigate the effect of different doses of febuxostat combined with beraprost sodium on renal function and oxidative stress in patients with chronic kidney disease(CKD)accompanied by hyperuricemia(HUA).Methods A total of 225 patients with CKD accompanied by HUA were randomly divided into high-dose group(febuxostat 80 mg/d),moderate-dose group(febuxostat 40 mg/d)and low-dose group(febuxostat 20 mg/d).All patients were treated with beraprost sodium.Before and at 12 weeks after treatment,fasting venous blood was collected to measure serum creatinine(Ser),blood urea nitrogen(BUN),superoxide dismutase(SOD),and malondialdehyde(MDA).At the same time,morning urine was taken to measure 24-hour urine protein content.At 4,8,and 12 weeks after treatment,the rate of the patients with blood uric acid levels in the normal range and the incidence of adverse reactions during treatment were measured.Results After 12 weeks of treatment,Ser,BUN,and 24 h urinary protein in 3 groups were significantly decreased when compared with before treatment,and they were high-dose group<moderate-dose<low-dose groups(P<0.05).After 12 weeks of treatment,SOD in 3 groups was significantly higher than before treatment,while MDA was significantly lower than before treatment.SOD level was high dose group>moderate dose>low dose group,while MDA level was high dose group<moderate dose<low dose group(P<0.05).The rate of the patients with blood uric acid levels in the normal range in high-dose group was higher than that in moderate-and low-dose groups at 4 weeks,8 weeks and 12 weeks after treatment(P<0.05).The total incidence of adverse reactions in high-dose group was higher than that in moderate-dose and low-dose groups(P<0.05).There was no significant difference in the incidence of adverse reactions between moderate-dose and low-dose groups(P>0.05).Conclusion Febuxostadat(80 mg/d)combined with beraprost sodium in treating CKD accompanied by HUA exhibits a good effect on renal function and oxidative stress index.