Effects of Allopurinol on the Progression of Chronic Kidney Disease

In RCT stopped early due to slow recruitment after 369 of 620 intended patients with CKD and high risk of progression were randomised, urate-lowering treatment with allopurinol did not slow decline in eGFR vs. placebo (change eGFR −3.33 vs.−3.23ml/min/1.73m2/yr, respectively).

SPS commentary:

This is one of two studies in New England Journal Medicine addressing the use of urate-lowering therapy for the prevention of kidney disease progression. In the Preventing Early Renal Loss in Diabetes (PERL) trial in patients with type 1 diabetes mellitus and CKD stages 1 to 3, allopurinol did not slow the rate of GFR decline after 3 years, compared to placebo.


According to an editorial, the potential role of uric acid in the progression of kidney disease has been argued about for decades and epidemiologic studies consistently implicate serum uric acid as a risk factor for CKD; though in one study, statistical correction for the effects of hypertension or cardiovascular disease caused the apparent interaction to fade. It suggests that the challenge in interpreting such evaluations is that if serum uric acid contributes to CKD progression in part by the exacerbation of hypertension or cardiovascular disease, then correcting for those contributions may substantially attenuate the association and obscure a mechanistic link. It notes that observational studies, have also found the association between elevated serum uric acid and progression of CKD is strongest in younger patients, those with less severe CKD, and those without proteinuria. It adds that intention-to-treat analyses, as in the current studies, provide guidance about the real-world efficacy of clinical interventions, but generalisations must be made with caution as these trials did not address urate-lowering therapy, either pharmacologic or dietary, in younger patients or in those with earlier stages of CKD; more high-quality RCTs are needed.


New England Journal of Medicine

Resource links:


PERL study