Uric acid-lowering therapy is associated with a higher risk for new-onset chronic kidney disease (CKD) among patients with baseline serum uric acid levels of 8 mg/d or less, a new study finds. The therapy did not change the risk among individuals with higher baseline serum uric acid levels.

Among 269,651 patients (94% male) with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2 and no albuminuria treated at US Veterans Affairs health care facilities from 2004 to 2019, a total of 29,501 patients (10.9%) started uric acid-lowering therapy. The vast majority (99.7%) received allopurinol. Of the full cohort, 21.7% eventually experienced an eGFR decline to less than 60 mL/min/1.73 m2, 25.5% new-onset albuminuria, and 0.2% end-stage kidney disease (ESKD).

After propensity-score matching, use vs nonuse of uric acid-lowering therapy was associated with a significant 15% higher risk of eGFR decline to less than 60 mL/min/1.73 m2 and a significant 5% higher risk of albuminuria in the overall cohort, Csaba P. Kovesdy, MD, of Memphis VA Medical Center in Tennessee, and colleagues reported in JAMA Network Open. Allopurinol use did not decrease the risk for ESKD.

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Among individuals with baseline serum uric acid levels of 8 mg/dL or less, uric acid-lowering therapy was significantly associated with 24% and 7% increased risks for an eGFR less than 60 mL/min/1.73 m2 and albuminuria, respectively. The investigators did not find these associations among those with higher baseline serum uric acid levels.

“These results do not support a direct benefit of urate lowering on the development of new-onset CKD, and support the results of recent large randomized clinical trials that found no benefit of allopurinol in delaying progression of established CKD,” Dr Kovesdy and his colleagues wrote.

The investigators noted that allopurinol may induce acute interstitial nephritis and lead to acute kidney injury, a major contributor to chronic kidney disease.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Hassan W, Shrestha P, Sumida K, et al. Association of uric acid-lowering therapy with incident chronic kidney disease. JAMA Netw Open. Published online June 1, 2022. doi:10.1001/jamanetworkopen.2022.15878