Vidar O Edvardsson1, Hrafnhildur L Runolfsdottir2, Unnur A Thorsteinsdottir3, Inger M Sch Agustsdottir4, G Steinunn Oddsdottir5, Finnur Eiriksson6, David S Goldfarb7, Margret Thorsteinsdottir8, Runolfur Palsson9. 1. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Children's Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: vidare@lsh.is. 2. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 3. Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 4. Children's Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 5. Department of Clinical Biochemistry, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 6. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; ArcticMass, Reykjavik, Iceland. 7. Nephrology Section, New York University Langone Medical Center, New York, NY, USA. 8. Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Reykjavik, Iceland; ArcticMass, Reykjavik, Iceland. 9. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Division of Nephrology, Internal Medicine Services, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: runolfur@landspitali.is.
Abstract
INTRODUCTION: Adenine phosphoribosyltransferase (APRT) deficiency is a rare, but significant, cause of kidney stones and progressive chronic kidney disease. The optimal treatment has not been established. The purpose of this pilot study was to compare the effect of the xanthine oxidoreductase inhibitors allopurinol and febuxostat on urinary 2,8-dihydroxyadenine (DHA) excretion in APRT deficiency patients. MATERIALS AND METHODS: Patients listed in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, currently receiving allopurinol therapy, were invited to participate. The trial endpoint was the 24-h urinary DHA excretion following treatment with allopurinol (400mg/day) and febuxostat (80mg/day). Urinary DHA was measured using a novel ultra-performance liquid chromatography - electrospray tandem mass spectrometry assay. RESULTS: Eight of the 10 patients invited completed the study. The median (range) 24-h urinary DHA excretion was 116 (75-289) mg at baseline, and 45 (13-112) mg after 14days of allopurinol therapy (P=0.036). At the end of the febuxostat treatment period, 4 patients had urinary DHA below detectable limits (<20ng/mL) compared with none of the participants following allopurinol treatment (P=0.036). The other 4 participants had a median 24-h urinary DHA excretion of 13.2 (10.0-13.4) mg at the completion of febuxostat therapy (P=0.036). CONCLUSION: Urinary DHA excretion in APRT deficiency patients decreased with conventional doses of both allopurinol and febuxostat. Febuxostat was, however, significantly more efficacious than allopurinol in reducing DHA excretion in the prescribed doses. This finding, which may translate into improved outcomes of patients with APRT deficiency, should be confirmed in a larger sample.
INTRODUCTION:Adenine phosphoribosyltransferase (APRT) deficiency is a rare, but significant, cause of kidney stones and progressive chronic kidney disease. The optimal treatment has not been established. The purpose of this pilot study was to compare the effect of the xanthine oxidoreductase inhibitors allopurinol and febuxostat on urinary 2,8-dihydroxyadenine (DHA) excretion in APRT deficiencypatients. MATERIALS AND METHODS:Patients listed in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, currently receiving allopurinol therapy, were invited to participate. The trial endpoint was the 24-h urinary DHA excretion following treatment with allopurinol (400mg/day) and febuxostat (80mg/day). Urinary DHA was measured using a novel ultra-performance liquid chromatography - electrospray tandem mass spectrometry assay. RESULTS: Eight of the 10 patients invited completed the study. The median (range) 24-h urinary DHA excretion was 116 (75-289) mg at baseline, and 45 (13-112) mg after 14days of allopurinol therapy (P=0.036). At the end of the febuxostat treatment period, 4 patients had urinary DHA below detectable limits (<20ng/mL) compared with none of the participants following allopurinol treatment (P=0.036). The other 4 participants had a median 24-h urinary DHA excretion of 13.2 (10.0-13.4) mg at the completion of febuxostat therapy (P=0.036). CONCLUSION: Urinary DHA excretion in APRT deficiencypatients decreased with conventional doses of both allopurinol and febuxostat. Febuxostat was, however, significantly more efficacious than allopurinol in reducing DHA excretion in the prescribed doses. This finding, which may translate into improved outcomes of patients with APRT deficiency, should be confirmed in a larger sample.
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