Time to soften stance against allopurinol and renal function?

Overcautious use of allopurinol due to misplaced fears it is detrimental to kidney function may be contributing to poor management of gout, research suggests.

Contrary to current guidelines on use of the urate-lowering therapy, the use of higher doses (300mg per day) of allopurinol was not associated with renal function deterioration and was in fact partly protective, results from UK cohort study have shown.

A review of records from the UK general practice database for 4760 newly-diagnosed gout patients starting allopurinol found that doses of 300mg per day were associated with a lower risk of developing renal function deterioration compared to a matched control group of people not using allopurinol.

The study, which focused on people with normal or near-normal  renal function at baseline, found that allopurinol use at 300mg a day or higher was associated with a 13% reduction in risk of developing chronic kidney disease stage 3 or higher during 12 years of follow up.

In contrast, starting allopurinol at doses lower than 300mg a day had no association with developing CKD.

Writing in JAMA Internal Medicine, the study investigators said  clinicians were cautious about using allopurinol, because gout often had chronic kidney disease as a co-morbidity and there were concerns about allopurinol hypersensitivity (AHS).

These fears had led to guideline recommendations to start with lower doses of allopurinol, despite there being little evidence to show that allopurinol is detrimental for renal function and some emerging evidence that it may be beneficial for renal dysfunction.

The study authors said their findings added to a growing evidence that decline in kidney function among gout patients has many potential causes, and may be worsened by hyperuricaemia.

Urate lowering-therapy may therefore have indirect protective effects on renal function by  preventing hyperuricaemia and also by preventing gout flares that make renally-harmful NSAID use more likely, they said.

“Because allopurinol did not appear to be associated with renal function decline, clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout,” they concluded.

An accompanying commentary noted that the guidelines that recommend lower doses of allopurinol are based on evidence from two small observational studies, one of which had a high proportion of patients who are at high risk of allopurinol hypersensitity.

“Clinicians already recognise that in many patients with gout higher doses of allopurinol can be prescribed without concerns about progression of CKD,” they added.

“The important message from this new study … is that allopurinol is unlikely to contribute to progression of CKD; indeed, it might even be protective, presumably by reducing the risk of urate nephropathy,” wrote Jonathan Zipursky and David Juurlink.

Some Australian treatment recommendations for gout still include cautionary advice to start with low doses of allopurinol (50–100 mg per day) and titrate up.

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