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. 2022 Jun 1;5(6):e2215878.
doi: 10.1001/jamanetworkopen.2022.15878.

Association of Uric Acid-Lowering Therapy With Incident Chronic Kidney Disease

Waleed Hassan  1   2 , Prabin Shrestha  2 , Keiichi Sumida  2 , Fridtjof Thomas  3 , Patrick L Sweeney  4 , Praveen K Potukuchi  2 , Connie M Rhee  5 , Elani Streja  5   6 , Kamyar Kalantar-Zadeh  5 , Csaba P Kovesdy  2   7
Affiliations

Association of Uric Acid-Lowering Therapy With Incident Chronic Kidney Disease

Waleed Hassan et al. JAMA Netw Open. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Thomas reported receiving grants from Relypsa-Vifor Pharma outside the submitted work. Dr Kalantar-Zadeh reported serving as a dialysis medical director for from DaVita and Fresenius and personal fees from Abbott, AbbVie, ACI Clinical (Cara Therapeutics), Akebia, Alexion, Amgen, Ardelyx, American Society of Nephrology, AstraZeneca, Aveo, BBraun, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, GlaxoSmithKline, Haymarket Media, Hofstra Medical School, International Federation of Kidney Foundations, International Society of Hemodialysis, International Society of Renal Nutrition & Metabolism, Japanese Society of Dialysis Therapy, Hospira, Kabi, Keryx, Kissei, Novartis, Novo Nordisk, OPKO, National Institutes of Health, National Kidney Foundations, Pfizer, Regulus, Relypsa, Resverlogix, Dr Schaer, Sandoz, Sanofi, Shire, Department of Veterans Affairs (VA), Takeda, Vifor, UpToDate, and ZS-Pharma outside the submitted work. Dr Kovesdy reported receiving personal fees from Abbott, Amgen, Akebia, AstraZeneca, Bayer, CSL Behring, Cara Therapeutics, Boehringer Ingelheim, Tricida, Vifor, and Rockwell outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Cohort Creation
eGFR, estimated glomerular filtration rate; ULT, uric acid–lowering therapy.
Figure 2.
Figure 2.. Hazard of Incident Estimated Glomerular Filtration Rate (eGFR) Less Than 60 mL/min/1.73 m2 and Albuminuria Associated With Uric Acid–Lowering Therapy in Propensity Score–Weighted Analyses
To convert uric acid to millimoles per liter, multiply by 0.0595. RAAS indicates renin angiotensin aldosterone system; NSAID, nonsteroidal anti-inflammatory drugs.
See this image and copyright information in PMC

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