Kidney Week

Abstract: SA-PO650

Effect of Allopurinol and Febuxostat on Plasma and Urine 2,8-Dihydroxyadenine: A Clinical Trial

Session Information

• Genetic Kidney Diseases: Models, Mechanisms, and Therapies
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Runolfsdottir, Hrafnhildur L., Landspitali, Reykjavik, Capital, Iceland

Hrafnhildur L. Runolfsdottir, MD, PhD

• Thorsteinsdottir, Unnur A., Haskoli Islands, Reykjavik, Iceland

Unnur A. Thorsteinsdottir, MS

• Agustsdottir, Inger M., Landspitali, Reykjavik, Capital, Iceland

Inger M. Agustsdottir, RN

• Thorsteinsdottir, Margret, Haskoli Islands, Reykjavik, Iceland

Margret Thorsteinsdottir, PharmD

• Palsson, Runolfur, Landspitali, Reykjavik, Iceland

Runolfur Palsson, MD, FASN

• Edvardsson, Vidar O., Landspitali, Reykjavik, Iceland

Vidar O. Edvardsson, MD

Background

In patients with adenine phosphoribosyltransferase (APRT) deficiency, treatment with allopurinol or febuxostat reduces urinary 2,8-dihydroxyadenine (DHA) excretion, preventing stone formation and progression of chronic kidney disease. The aim of this study was to determine the effects of allopurinol 400 and 800 mg/day and febuxostat 40 and 80 mg/day on plasma and urinary DHA levels in patients with APRT deficiency.

Methods

Patients with estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m² listed in the APRT Deficiency Registry of the Rare Kidney Stone Consortium were enrolled in a 168-day clinical trial. Following a 4-week washout period, patients were randomized to a single daily dose of allopurinol 400 mg or febuxostat 40 mg for 28 days, after which the dose was elevated to 800 mg of allopurinol and 80 mg of febuxostat. A second washout period was then followed by cross-over to the alternative study drug. Plasma and urine levels of DHA were measured using an ultra-performance liquid chromatography-tandem mass spectrometry assay, and the urinary excretion expressed as DHA/creatinine ratio.

Results

Seven patients completed the study. Their median (range) age was 57.7 (37.3-65.1) years; 3 were female. The median urinary DHA/creatinine ratio was 7.5 (4.3-14.0) ng/mmol off treatment, 2.1 (1.0-4.9) and 0.79 (0.2-2.2) on 400 and 800 mg of allopurinol, respectively, and 0.6 (0.3-1.0) and 0.6 (0.2-5.4) on 40 and 80 mg of febuxostat, respectively. The median plasma DHA concentration was 289 (216-432) ng/mL during both washout periods and 50 (32-95) ng/mL on 400 mg of allopurinol in 4 patients, while the other 3 patients had concentrations below the level of quantification (BLQ). On allopurinol 800 mg/day, the plasma DHA concentration was BLQ in all but 2 patients, and BLQ in all but 1patient on both doses of febuxostat.

Conclusion

Urinary DHA excretion and plasma concentration was lower in patients on allopurinol 800 mg/day compared to 400 mg/day. There was no apparent difference in DHA plasma concentration or urinary DHA excretion between the two prescribed febuxostat doses. Febuxostat was more efficacious than allopurinol in the prescribed doses.

Funding

• Government Support – Non-U.S.