Gout Drug May Protect Against Chronic Kidney Disease

Allopurinol (multiple brands), used to manage gout, may protect against chronic kidney disease (CKD), according to results of a study published onlineOctober 8 in JAMA Internal Medicine.

Only one third of patients with gout in the United States take urate-lowering medication. One factor that may contribute to the low rate is the high prevalence of comorbid CKD of stage 3 or higher and concern that the drugs could hasten kidney failure. CKD affects 20% of people with gout, compared with 5% of those who do not have gout.

The American College of Rheumatology has suggested that patients with advanced kidney disease and gout begin treatment with allopurinol at lower starting doses than other patients.

The precaution against use of the drug is largely due to concern about the possibility of allopurinol hypersensitivity syndrome affecting renal function.

In the current study, Ana Beatriz Vargas-Santos, MD, from the State University of Rio de Janeiro, in Brazil, and colleagues investigated whether allopurinol, at a dosage at or above 300 mg/day, is detrimental to renal function in patients with gout.

The team assessed the association of allopurinol use in gout with the risk of developing CKD of stage 3 or higher within a few years among a propensity score–matched prospective cohort composed of 4760 patients newly diagnosed with gout who were taking at least 300 mg/day of allopurinol and the same number of gout patients who were not taking the drug. The patients had been diagnosed from 2000 through 2014. The mean age of the patients was 57 years, and they had normal or near-normal kidney function at baseline.

Using data from the Health Improvement Network, an electronic health records database from general practitioners in the United Kingdom, the researchers found that 579 patients (12.2%) taking allopurinol developed CKD of stage 3 or higher within 5 years, compared with 623 patients (13.1%) in the group that did not receive the drug.

In an adjusted analysis, patients taking allopurinol had a 13% reduced risk of developing CKD of stage 3 or higher compared with those not taking the drug (propensity score-matched hazard ratio, .87; 95% confidence interval, 0.77 - 0.97).

The authors note that at the time of analysis, 70% of each group had stage 2 CKD, and the remainder had stage 1 disease.

They conclude that initiating allopurinol at a dosage of at least 300 mg/day to treat gout was not only safe but possibly protective against the development of CKD.

"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 write.

"Ultimately, we hope these results will be disseminated to PCPs [primary care physicians] and internists taking care of patients with gout (since the bulk of patients with gout are managed in primary care) so that allopurinol is not held or stopped when a patient experiences a creatinine bump," said corresponding author and rheumatologist Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at the Boston University School of Medicine and School of Public Health, in a news release,

In an invited commentary, Jonathan Zipursky, MD, and David N. Juurlink, MD, PhD, both from the University of Toronto, Canada, applaud the use of "real-world" observational studies to investigate the current practice of starting patients with gout and CKD on a lower dose of allopurinol. They note that the recommendation initially came from studies in which there was an overrepresentation of patients of Chinese ethnicity. Such patients are at higher risk for allopurinol hypersensitivity.

"The important message from this new study, however, 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," the commentators conclude.

A limitation of the study is a surveillance bias arising from more frequent and extended monitoring of patients who were taking the drug compared to those who were not taking it; this possibly resulted in more rigorous examination of renal function.

Dr Vargas-Santos has received speaker's fees and support for international medical events from Grünenthal. The other investigators and the writers of the commentary have disclosed no relevant financial relationships.

JAMA Int Med. Published online October 8, 2018
Shutterstock photo

Nessy Sipling