Uric acid-lowering therapy associated with higher risk of new-onset CKD: JAMA

USA: In patients with kidney function within the reference range, uric acid-lowering therapy may increase the risk of new-onset chronic kidney disease (CKD), suggests study data published in the JAMA Network Open. The study findings disapprove of starting uric acid-lowering therapy as a means to prevent the development of CKD.

Globally, approximately 850 million people are affected by kidney diseases. Various efforts are made to identify treatable risk factors of CKD, due to its high incidence and prevalence rate. Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels lead to the progression of CKD. Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the association of uric acid–lowering therapies with the development of new-onset CKD in patients with estimated glomerular filtration rate (eGFR) within the reference range and no albuminuria is unclear.

Waleed Hassan, North Mississippi Medical Center, USA, and his colleagues examined the association of initiating uric acid-lowering therapy with the incidence of CKD by conducting a cohort study of 269 651 patients with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m2 and no albuminuria, treated at US Department of Veterans Affairs health care facilities (2004 – 2019).

Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. The main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease.

The study data showed that

• Initiating uric acid-lowering therapy increased the risk of developing an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 and albuminuria in patients compared to those that did not begin therapy

• Uric acid-lowering therapy was not associated with the risk of end-stage kidney disease.

• Uric acid levels less than or equal to 8 mg/dL were associated with an increased incidence of eGFR less than 60 mL/min/1.73m2, whereas levels above 8 mg/dL were not.

The authors conclude that uric acid–lowering therapy is not associated with beneficial kidney outcomes, but it elevates the risk of new-onset CKD in patients with baseline serum uric acid levels of 8 mg/dL or lower.

The causal effect of uric acid–lowering therapies, especially allopurinol, in patients with no preexisting CKD needs to be assessed in adequately designed randomized clinical trials. The lack of such trials and the preponderance of existing evidence opposes the administration of uric acid–lowering therapies to prevent the development of CKD, the authors wrote.

Reference: 

Hassan W, Shrestha P, Sumida K, et al. Association of Uric Acid–Lowering Therapy With Incident Chronic Kidney Disease. JAMA Netw Open. 2022;5(6):e2215878. doi:10.1001/jamanetworkopen.2022.15878