title: Recurrent 2,8-dihydroxyadenine nephropathy: a rare but preventable cause of renal allograft failure.
abstract: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8-dihydroxyadenine (2,8-DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8-DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5-312) weeks following the transplant procedure. Patients had delayed graft function (n=2), acute-on-chronic (n=5) or acute (n=1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8-DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8-DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n=7), remained stable (n=1) or worsened (n=1). At last follow-up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8-DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.
authors.affiliation: Department of Nephrology-Transplantation, Necker Hospital, APHP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France; Département Biologie cellulaire, INSERM U1151, Institut Necker Enfants Malades, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Zaidan
authors.forename: R
authors.initials: R
authors.lastname: Palsson
authors.forename: E
authors.initials: E
authors.lastname: Merieau
authors.forename: E
authors.initials: E
authors.lastname: Cornec-Le Gall
authors.forename: A
authors.initials: A
authors.lastname: Garstka
authors.forename: U
authors.initials: U
authors.lastname: Maggiore
authors.forename: P
authors.initials: P
authors.lastname: Deteix
authors.forename: M
authors.initials: M
authors.lastname: Battista
authors.forename: E-R
authors.initials: ER
authors.lastname: Gagné
authors.forename: I
authors.initials: I
authors.lastname: Ceballos-Picot
authors.forename: J-P
authors.initials: JP
authors.lastname: Duong Van Huyen
authors.forename: C
authors.initials: C
authors.lastname: Legendre
authors.forename: M
authors.initials: M
authors.lastname: Daudon
authors.forename: V O
authors.initials: VO
authors.lastname: Edvardsson
authors.forename: B
authors.initials: B
authors.lastname: Knebelmann
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency*; D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008661:Metabolism, Inborn Errors / Q000209:etiology* / Q000503:physiopathology; D008875:Middle Aged; D012008:Recurrence; D052878:Urolithiasis / Q000209:etiology* / Q000503:physiopathology
chemical_list: D000228:Adenine Phosphoribosyltransferase
keywords: Clinical research/practice; kidney (allograft) function/dysfunction; kidney disease; kidney transplantation/nephrology