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. 2025 Mar;38(2):597-607.
doi: 10.1007/s40620-024-02179-0. Epub 2025 Jan 8.

Association between urate-lowering therapy and kidney failure in patients with chronic kidney disease

Agathe Mouheb  1   2 , Oriane Lambert  3 , Natalia Alencar de Pinho  3 , Christian Jacquelinet  4 , Maurice Laville  5 , Christian Combe  6   7 , Denis Fouque  5   8 , Luc Frimat  9   10 , Ziad A Massy  3   11   12 , Solène M Laville  1   2 , Sophie Liabeuf  13   14 ; Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group
Collaborators, Affiliations

Association between urate-lowering therapy and kidney failure in patients with chronic kidney disease

Agathe Mouheb et al. J Nephrol. 2025 Mar.

Abstract

Background: Hyperuricemia is a hallmark of gout and a suspected risk factor for the progression of chronic kidney disease (CKD). However, the impact of urate-lowering therapy on CKD progression is subject to debate. The objective of the present study was to describe the prevalence of inappropriate urate-lowering therapy prescriptions and evaluate the association between urate-lowering therapy prescription and the progression of kidney disease in patients with CKD.

Methods: CKD-REIN is a French, nationwide, prospective cohort of 3,033 nephrology outpatients with CKD (eGFR < 60 mL/min/1.73 m2). Prescriptions of urate-lowering therapy drugs (allopurinol or febuxostat) were recorded prospectively. The appropriateness of each prescription was evaluated according to the patient's kidney function at baseline and during follow-up. Propensity score-matched, cause-specific Cox proportional hazards regression models were used to assess the association between incident urate-lowering therapy use and CKD progression (defined as the initiation of kidney replacement therapy (KRT) but also in other ways).

Results: At baseline, 987 of the 3009 patients included in this study (median age: 69; men: 66%) were receiving urate-lowering therapy; 396 of these 987 patients were receiving an inappropriate prescription with regard to their kidney function. During a 5-year follow-up period, 70% of the 396 urate-lowering therapy prescriptions remained inappropriate. In the propensity score-matched cohort (n = 674), 136 patients started KRT. Compared with non- urate-lowering therapy use, urate-lowering therapy use was not significantly associated with a slowing in CKD progression, regardless of the definition used (HRKRT 0.89, 95% CI 0.67-1.20).

Conclusions: Our real-world data emphasized the lack of reassessment of urate-lowering therapy prescriptions in patients with CKD. Urate-lowering therapy was not associated with a slowing of CKD progression.

Keywords: Chronic kidney disease; Disease progression; Drug use; Inappropriate prescribing; Pharmacoepidemiology; Urate-lowering therapy.

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Conflict of interest statement

Declarations. Conflict of interest: A.M., S.M.L., S.L., O.L., M.L. have nothing to declare. Z.A.M. reports having received grants for CKD-REIN and other research projects from Amgen, Baxter, Fresenius Medical Care, GlaxoSmithKline, Merck Sharp and Dohme-Chibret, Sanofi-Genzyme, Lilly, Otsuka, AstraZeneca, Vifor and the French government, as well as fees and grants to charities from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. N.A.P. declares financial support from pharmaceutical companies who are members of the CKD-REIN public–private partnership: Fresenius Medical Care, GlaxoSmithKline, Vifor France, and Boehringer Ingelheim; all grants were made to Paris Saclay University. D.F. has received grants and lecture fees from Astellas, GlaxoSmithKline, Dr Schar, Theradial, and AstraZeneca. Ethical approval: The study protocol was approved by the institutional review board at the French National Institute of Health and medical research (INSERM; reference: IRB00003888). Statement of human and animal rights: This article does not contain any studies with animals. Informed consent to participate: Patients provided informed consent to participate.

References

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