Key points What is the association of uric acid-lowering therapy with the development of new-onset chronic kidney disease (CKD)? Findings In this cohort study of 269,651 patients with an estimated glomerular filtration rate of at least 60 ml/min/1.73 m2 and no albuminuria, there was no beneficial association between the initiation of uric acid-lowering therapy and the incidence of CKD. Uric acid-lowering therapy was associated with a significantly increased risk of new-onset CKD. Meaning These findings do not support the initiation of uric acid-lowering therapy as a means to prevent the development of CKD. |
Importance
Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with an increased risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). .
Treatment of hyperuricemia in patients with pre-existing CKD has not been shown to improve renal outcomes, but associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within the reference range and without albuminuria is unclear.
Aim
To examine the association of initiating uric acid-lowering therapy with the incidence of CKD.
Design, scope and participants
This cohort study included patients with eGFR of 60 ml/min/1.73 m2 or greater and without albuminuria treated at US Department of Veterans Affairs healthcare facilities, used to minimize confounding. The data was analyzed from 2020 to 2022.
Exposure
Recently started uric acid reducing therapy.
Main results and measures
The main outcomes were incidences of eGFR less than 60 ml/min/1.73 m2, new-onset albuminuria, and end-stage renal disease.
Results
A total of 269,651 patients were evaluated (mean [SD] age, 57.4 [12.5] years; 252,171 [94%] men). Of these, 29,501 patients (10.9%) initiated treatment to reduce uric acid and 240,150 patients (89.1%) did not.
Baseline characteristics, including serum uric acid level, were similar between treated and untreated patients after propensity score weighting.
In the overall cohort, uric acid-lowering treatment was associated with an increased risk of incident eGFR less than 60 mL/min/1.73 m2 (weighted hazard ratio [SHR], 1.15 [95% CI]. 1.10-1.20; P < .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P < .001]), but was not associated with disease risk end-stage renal disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87).
In subgroup analyses, the association of uric acid-lowering therapy with worse renal outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less .
Conclusions and relevance
These findings suggest that in patients with renal function within the reference range , uric acid-lowering therapy was not associated with beneficial renal outcomes and may be associated with potential harm in patients with less elevated serum uric acid levels.
Discussion
This cohort study found that uric acid-lowering therapy was not associated with beneficial renal outcomes, including the incidence of eGFR less than 60 ml/min/1.73 m2, albuminuria, or ESKD.
Uric acid-lowering therapy was associated with an increased risk of new-onset CKD, including the development of eGFR less than 60 mL/min/1.73 m2 and new-onset albuminuria, in patients with baseline serum uric acid levels. 8 mg/dL or less.
The causal effect of uric acid-lowering therapies, and especially allopurinol, in patients without pre-existing CKD should be examined in adequately powered randomized clinical trials. In the absence of such trials, the preponderance of existing evidence does not support the administration of uric acid-lowering therapies as a means to prevent the development of CKD.
