Allopurinol Does Not Reduce CKD Progression

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Urate-lowering therapy does not reduce the risk of progression in patients with chronic kidney disease (CKD), reports The New England Journal of Medicine.

The “Controlled Trial of Slowing of Kidney Disease Progression from the Inhibition of Xanthine Oxidase” (CKD-FIX) enrolled adults with stage 3 or 4 CKD (urinary albumin:creatinine ratio of 265 or higher or estimated glomerular filtration rate [eGFR] at least 3.0 mL/min/1.73 m2) and no history of gout. Patients were assigned to allopurinol, 100 to 300 mg/d, or placebo. The main outcome of interest was change in eGFR from baseline to 104 weeks.

Planned sample size was 620, but enrollment was stopped after 369 patients due to slow recruitment. On analysis of 363 patients, mean change in eGFR was −3.33 mL/min/1.73 m2/y in the allopurinol group and −3.23 mL/min/1.73 m2/y in the placebo group. Rates of serious adverse events were 46% and 44%, respectively.

Secondary outcomes were also similar, including a composite of 40% decrease in eGFR, end stage kidney disease, or death from any cause. After dose escalation, mean serum rate level was 5.3 mg/dL in the allopurinol group and 8.2 mg/dL in the placebo group.

High serum urate levels are a risk factor for progression of chronic kidney disease (CKD), but it is unclear whether there is any causal association. Evidence on the use of urate-lowering medications to slow the progression of CKD is limited.

The CKD-FIX results find no benefit of allopurinol in slowing CKD progression in high-risk patients. The lack of effect is despite a sustained 35% reduction of serum urate levels with allopurinol, compared to placebo [Badver SV, et al. Effects of allopurinol on the progression of chronic kidney disease. N Engl J Med 2020; 382:2504−2513].

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