#1135 Evaluation of the adequacy of urate lowering therapy prescriptions in patients with chronic kidney disease: results from the CKD-REIN cohort
Authors: Mouheb Agathe , Lambert Oriane , de Pinho Natalia Alencar , Jacquelinet Christian , Laville Maurice , Combe Christian , Fouque Denis , Frimat Luc , Stengel Benedicte , Massy Ziad , Laville Solene M , Liabeuf Sophie 
Published: May 2024

Abstract

Background and Aims
Urate Lowering Therapy (ULT) is frequently prescribed to patients with chronic kidney disease (CKD). However, these prescriptions are often inadequate when considering kidney function. Studies evaluating the appropriateness of ULT in the CKD population are predominantly cross-sectional. Yet, the evolution and reassessment of prescriptions remain unexplored in this context. This study aims to assess the prevalence of inappropriate ULT prescriptions (whether contraindications or inappropriately high doses) with regard to kidney function in patients with CKD.

Method
We used 5-year longitudinal data from the CKD-REIN cohort, a nationwide sample of 3033 nephrology outpatients with moderate-to-advanced CKD. Prescriptions for colchicine, used in the treatment of acute gout attacks, and ULT, such as allopurinol and febuxostat, were prospectively recorded. An inappropriate prescription was defined as the reported prescription of either a contraindicated drug, an indicated drug at an inappropriately high dose level, or a non-recommended prescription relative to the patient's eGFR, as estimated with de-indexed CKD-EPI equation and according to the European (or French if not available) summary of product characteristics. For patients initiating ULT during follow-up, uric acid levels were compared six months before and after the initiation of ULT.

Results
At baseline, 987 (33%) out of the 3033 included patients (mean ± standard deviation age 67 ± 13 years, 65% men) were prescribed ULT, with 781 (26%) receiving allopurinol and 206 (7%) receiving febuxostat. Compared to patients without a prescription for ULT, those with a ULT prescription were more frequently male, older, had lower kidney function, higher cardiovascular comorbidities, and were more commonly prescribed diuretics and inhibitors of the renin-angiotensin system. Moreover, their uric acid levels were lower (patients with ULT prescription 377.0 ± 110.4 µmol/L versus without ULT prescription 456.5 ± 116.4 µmol/L, p &lt; 0.001). Notably, 316 (40%) allopurinol prescriptions were prescribed at inappropriately high dosages, while 77 (37%) febuxostat prescriptions were not recommended (resulting in a total of 393 (40%) inappropriate ULT prescriptions at baseline). Of the 54 colchicine prescriptions, one-third (n = 18) were contraindicated according to kidney function and nine were prescribed “on-demand” for crisis anticipation.
During a median follow-up of 5.0 [1st-3rd quartile, 4.0–5.1] years, 253 patients were newly prescribed allopurinol and 176 were newly prescribed febuxostat, 54 (21%) out of 253 new allopurinol prescriptions were at inappropriately high dosages, and 68 (39%) out of the 176 new febuxostat prescriptions were not recommended based on the patient's kidney function (Figure). The majority of initially inappropriate ULT prescriptions (n = 393) remained so during follow-up (274 (70%)). Among the 179 patients initiating ULT during follow-up and with available data on uric acid levels, there was a significant decrease in uric acid levels after ULT initiation compared to before initiation (before: 494.5 ± 146.2 µmol/L versus after 408.5 ± 130.9 µmol/L, p &lt; 0.001). A total of 197 patients had initiated colchicine during follow-up, with 61 (31%) receiving contraindicated prescriptions, and 18 (9%) having “on-demand” prescriptions.

Conclusion
Our findings emphasize the lack of reassessment of ULT prescriptions during the follow-up of patients with CKD. Colchicine prescriptions in case of severe kidney impairment persist despite contraindications. Further evaluation is required to understand the association between ULT prescriptions and the progression of kidney disease.