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Association of Uric Acid-Lowering Therapy With Incident Chronic Kidney Disease
Waleed Hassan1,2, Prabin Shrestha2, Keiichi Sumida2
1Department of Medicine, North Mississippi Medical Center, Tupelo.
Insights
Uric acid-lowering therapy did not improve kidney outcomes in patients with normal kidney function and may increase risks for those with lower uric acid levels. This highlights potential harms of these treatments in specific patient groups.
Area of Science:
- Nephrology
- Pharmacology
- Public Health
Background:
- Elevated serum uric acid is linked to hypertension, cardiovascular disease, mortality, and chronic kidney disease (CKD) progression.
- The impact of uric acid-lowering therapies on new-onset kidney disease in patients with normal estimated glomerular filtration rate (eGFR) and no albuminuria remains unclear.
Purpose of the Study:
- To investigate the association between initiating uric acid-lowering therapy and the incidence of CKD in patients with preserved kidney function.
Main Methods:
- A cohort study of 269,651 US Department of Veterans Affairs patients with eGFR ≥ 60 mL/min/1.73 m² and no albuminuria from 2004-2019.
- Clinical trial emulation with propensity score weighting was used to minimize confounding.
- Outcomes included new-onset eGFR < 60 mL/min/1.73 m², new-onset albuminuria, and end-stage kidney disease.
Main Results:
- Uric acid-lowering therapy was associated with a higher risk of developing eGFR < 60 mL/min/1.73 m² (SHR, 1.15) and new-onset albuminuria (SHR, 1.05).
- No association was found with end-stage kidney disease risk (SHR, 0.96).
- Harmful associations were primarily observed in patients with baseline serum uric acid levels of 8 mg/dL or less.
Conclusions:
- In patients with normal kidney function, uric acid-lowering therapy is not linked to improved kidney outcomes.
- These therapies may pose potential harm, particularly in individuals with less severely elevated serum uric acid levels.
Importance:
Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear.
Objective:
To examine the association of initiating uric acid-lowering therapy with the incidence of CKD.
Design, Setting, And Participants:
This cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022.
Exposure:
Newly started uric acid-lowering therapy.
Main Outcomes And Measures:
The main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease.
Results:
A total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). 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. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard 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 the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney 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 kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.
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