Department of Renal Medicine, St George Hospital.
Renal and Metabolic Division, the George Institute for Global Health, University of New South Wales Medicine, Sydney, New South Wales.
Curr Opin Nephrol Hypertens. 2021 May 1;30(3):346-352. doi: 10.1097/MNH.0000000000000699.
Several observational studies have shown that hyperuricemia is associated with chronic kidney disease (CKD) progression and is a potential therapeutic target in people with CKD. This review discusses the results of three recently published placebo-controlled randomized trials evaluating the effect of urate-lowering treatment on the progression of CKD with at least 2 years of follow-up.
The Febuxostat versus Placebo Randomized Controlled Trial Regarding Reduced Renal Function in Patients with Hyperuricemia Complicated by Chronic Kidney Disease Stage 3 trial evaluated the effect of febuxostat in 443 patients with stage 3 CKD (mean estimated glomerular filtration rate [eGFR] 45 mL/min/1.73 m2) and asymptomatic hyperuricemia (mean serum urate 7.8 mg/dL). The Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase and Preventing Early Renal Loss in Diabetes trials respectively evaluated the effect of allopurinol in 369 adults with stage 3 or 4 CKD (mean eGFR 31.7 mL/min/1.73 m2, mean serum urate 8.2 mg/dL) with high progression risk and 530 patients with type 1 diabetes and diabetic kidney disease (mean eGFR 74.7 mL/min/1.73 m2, mean serum urate 6.1 mg/dL). Despite the large and sustained reductions in serum urate levels in all 3 trials, urate-lowering treatment with febuxostat or allopurinol did not result in clinically meaningful improvement in kidney outcomes.
The results of large and well-designed placebo-controlled trials do not support the use of urate-lowering therapy to slow the progression of CKD.
几项观察性研究表明，高尿酸血症与慢性肾脏病（CKD）进展有关，是 CKD 患者的潜在治疗靶点。本综述讨论了最近发表的三项安慰剂对照随机临床试验的结果，这些试验评估了降尿酸治疗对至少 2 年随访的 CKD 进展的影响。
高尿酸血症合并慢性肾脏病 3 期患者中尿酸降低对肾功能的影响——非布司他与安慰剂随机对照试验评估了 443 例 3 期 CKD（平均估计肾小球滤过率[eGFR]45ml/min/1.73m2）和无症状高尿酸血症（平均血清尿酸 7.8mg/dL）患者中使用非布司他的效果。抑制黄嘌呤氧化酶延缓肾脏病进展和预防糖尿病早期肾脏丢失的临床试验分别评估了别嘌醇在 369 例 3 期或 4 期 CKD（平均 eGFR 31.7ml/min/1.73m2，平均血清尿酸 8.2mg/dL）和高进展风险的患者和 530 例 1 型糖尿病和糖尿病肾病患者（平均 eGFR 74.7ml/min/1.73m2，平均血清尿酸 6.1mg/dL）中的效果。尽管所有 3 项试验中的血清尿酸水平均大幅且持续降低，但非布司他或别嘌醇的降尿酸治疗并未导致肾脏结局的临床显著改善。
大型和精心设计的安慰剂对照试验的结果不支持使用降尿酸疗法来减缓 CKD 的进展。
