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

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 (HR_KRT 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.