非布司他对慢性肾脏病3~5期合并高尿酸血症患者的肾脏保护作用及相关机制

Protective effect of Febuxostat on stage 3-5 chronic kidney disease complicated with hyperuricemia and its mechanism

摘要:

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。

Abstract:

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.