目的 探讨非布司他对慢性肾脏病3～5期合并高尿酸血症的肾脏保护作用及对氧化应激的影响.方法 采用非布司他治疗45例慢性肾脏病3～5(CKD3～5)期合并高尿酸血症患者,随访24周,根据血尿酸下降值将患者分为4组:A组(≤4 mg/dl)、B组(＞4 ～5 mg/dl)、C组(＞5～6 mg/dl)及D组(＞6 mg/dl),比较各组患者临床资料、肾小球滤过率(eGFR)、不良反应以及氧化应激指标的影响.结果 4组患者性别、年龄、体重指数、饮酒、痛风病史、痛风石、尿酸、高血压、糖尿病及心血管疾病等比较,差异无统计学意义(P＞0 05),治疗24周后4组eGFR均有不同程度降低,与A、B、C组比较,D组降幅最小.治疗前后D组与A、B、C组比较,差异有统计学意义(P＜0.05).D组血清丙二醛、晚期氧化蛋白产物降幅最大,血清超氧化物歧化酶活性上升幅度最大.4组患者急性痛风发作、肝功能、恶心及皮疹比较,差异无统计学意义(P＞0.05).结论 非布司他治疗肾功能受损的CKD3～5期合并高尿酸血症及痛风的透析前患者,安全有效,副作用小,可能通过其降低血尿酸水平,增强抗氧化作用,延缓eGFR的下降速度,保护肾功能.%Objectives To investigate the protective effect of Febuxostat on chronic kidney disease (CKD) complicated with hyperuricemia and its mechanism.Methods Stage 3-5 CKD patients with hyperuricemia who received Febuxostat for 24 weeks were divided into 4 groups according to the level of serum uric acid (sUA):group A (≤ 4 mg/dl),group B (＞4-5 mg/dl),group C (＞ 5-6 mg/dl) and group D (＞ 6 mg/dl).The clinical data,estimated glomerular filtration rate (eGFR),the incidences of adverse events and the indexes of oxidative stress were compared among the four groups.Results Forty-five patients were enrolled in the study.Univariate analysis revealed that gender,age,BMI,drinking,history of gout,gouty tophi,uric acid,hypertension,diabetes and cardiovascular diseases were not significantly different among the four groups (P ＞0.05).After 24 weeks of Febuxostat treatment,eGFR decreased in all four groups,the group D had the smallest decrease.Compared with the groups A,B and C,the group D had the the maximum decrease in serum malondialdehyde and advanced oxidative protein products and the maximum increase in serum superoxide dismutase activity (P＜ 0.05).There was no significant difference in acute gout attack,liver function,nausea or rash among the four groups (P ＞ 0.05).Conclusions Febuxostat is a safe,effective and low sideeffect drug for stage 3-5 CKD patients with hyperuricemia and gout.It decreases the level of sUA,enhances anti-oxidation,slows down the decreasing rate of eGFR and eventually protects renal function.
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