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Comparative Study
. 2018 Feb:48:75-79.
doi: 10.1016/j.ejim.2017.10.007. Epub 2017 Dec 12.

Comparison of the effect of allopurinol and febuxostat on urinary 2,8-dihydroxyadenine excretion in patients with Adenine phosphoribosyltransferase deficiency (APRTd): A clinical trial

Vidar O Edvardsson  1 , Hrafnhildur L Runolfsdottir  2 , Unnur A Thorsteinsdottir  3 , Inger M Sch Agustsdottir  4 , G Steinunn Oddsdottir  5 , Finnur Eiriksson  6 , David S Goldfarb  7 , Margret Thorsteinsdottir  8 , Runolfur Palsson  9
Affiliations
Comparative Study

Comparison of the effect of allopurinol and febuxostat on urinary 2,8-dihydroxyadenine excretion in patients with Adenine phosphoribosyltransferase deficiency (APRTd): A clinical trial

Vidar O Edvardsson et al. Eur J Intern Med. 2018 Feb.

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.

Keywords: Chronic kidney disease; Crystal nephropathy; Kidney stones; Nephrolithiasis; Xanthine oxidoreductase inhibitors.

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Conflict of interest statement

Conflict of Interests

The results presented in this paper have not been published previously in whole or part, except in abstract form. None of the authors declared financial or other conflicting interests.

References

    1. Edvardsson V, Palsson R, Olafsson I, Hjaltadottir G, Laxdal T. Clinical features and genotype of adenine phosphoribosyltransferase deficiency in iceland. Am J Kidney Dis. 2001;38:473–80. - PubMed
    1. Edvardsson VO, Goldfarb DS, Lieske JC, Beara-Lasic L, Anglani F, Milliner DS, et al. Hereditary causes of kidney stones and chronic kidney disease. Pediatr Nephrol. 2013;28:1923–42. - PMC - PubMed
    1. Sahota A, Tischfield J, Kamatani N, Simmonds H. Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadenine lithiasis. In: Scriver CRBA, Sly WS, Valle D, Vogelstein B, Childs B, editors. The Metabolic and Molecular Bases of Inherited Disease. 8. New York, NY: McGraw-Hill; 2001. pp. 2571–84.
    1. Runolfsdottir HL, Palsson R, Agustsdottir IM, Indridason OS, Edvardsson VO. Kidney Disease in Adenine Phosphoribosyltransferase Deficiency. Am J Kidney Dis. 2016;67:431–8. - PMC - PubMed
    1. Zaidan M, Palsson R, Merieau E, Cornec-Le Gall E, Garstka A, Maggiore U, et al. Recurrent 2,8-dihydroxyadenine nephropathy: a rare but preventable cause of renal allograft failure. Am J Transplant. 2014;14:2623–32. - PMC - PubMed

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