Febuxostat for the Prevention of Recurrent 2,8-dihydroxyadenine Nephropathy due to Adenine Phosphoribosyltransferase Deficiency Following Kidney Transplantation

Abstract

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that results in irreversible renal damage due to 2,8-dihydroxyadenine (DHA) nephropathy. A 28-year-old man underwent living-related kidney transplantation for chronic kidney disease of unknown etiology. Numerous spherical brownish crystals observed in his urinary sediment on postoperative day 3 and were observed within the tubular lumen of renal allograft biopsy specimens on postoperative day 7. After a genetic diagnosis, febuxostat treatment was started on postoperative day 7, with the dosage gradually increased to 80 mg/day until complete the disappearance of 2,8-DHA crystals. Febuxostat prevented secondary 2,8-DHA nephropathy after kidney transplantation.

Nephrolithiasis and Nephrocalcinosis in Childhood—Risk Factor-Related Current and Future Treatment Options

“…Allopurinol also can be used in 2,8-Dihydroxyadeninuria, as well as hyperhydration and dietary restriction of adenine and purine. If allopurinol is not applicable, e.g., due to allergic reactions, single cases with successive treatment with febuxostat have been reported ( 66 ) and clinical experience supports these reports.…”

Adenine Phosphoribosyltransferase Deficiency: A Potentially Reversible Cause of CKD

“…The dosing of allopurinol is not straightforward. High doses of allopurinol 2 , 4 , 8 , S1 (up to 600 mg) and febuxostat (80 mg) 6 have been required to achieve effective inhibition of DHA crystalluria. Icelandic nephrologists at Landspitali Hospital (who also run the Rare Stone Group Consortium APRT registry) also have used a combination of high-dose 800 mg allopurinol and 80 mg febuxostat in some cases.…”

“…Reducing DHA production by xanthine oxidase inhibition is the cornerstone of pharmacological therapy for APRT deficiency. Allopurinol is the most used drug in this instance, whereas the addition or switch to febuxostat has been used in several cases 2, 6. Supportive therapy includes low purine diet and high fluid intake.…”

A deficiência de adenina fosforibosiltransferase leva à disfunção do aloenxerto renal em receptores de transplante renal: uma revisão sistemática

“…A triagem final com base no texto na íntegra envolveu os 33 artigos restantes, dos quais 13 foram excluídos devido a desfechos indesejados, dados incompletos e duplicação. Os 20 estudos contendo 30 amostras foram considerados para revisão final e análise qualitativa 1,2,7,8,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] . A visão geral detalhada de todos os 20 estudos elegíveis é fornecida como Arquivo Suplementar.…”