title: Crystalline nephropathy due to 2,8-dihydroxyadeninuria: an under-recognized cause of irreversible renal failure.
abstract: BACKGROUND
  2,8-dihydroxyadeninuria (DHA) disease (also called 2,8 dihydroxyadeninuria) is a rare autosomal recessive disorder caused by complete adenine phosphoribosyltransferase deficiency and typically manifests as recurrent nephrolithiasis. Only rare cases of DHA nephrolithiasis have been reported from the USA. Herein, we report three American patients who developed DHA crystalline nephropathy leading to end-stage renal disease (ESRD) with recurrence in the allograft.
  
  
  METHODS
  Three cases of DHA crystalline nephropathy were identified from the Renal Pathology Laboratory of Mayo Clinic. Detailed clinical and pathologic descriptions are provided.
  
  
  RESULTS
  All three patients were Caucasian adults with no history of obstructive nephropathy. Two patients had no history of nephrolithiasis and one had a single episode of stones 36 years prior to presentation. All patients presented with severe renal failure with a mean serum creatinine of 7.5 mg/dl. Renal biopsies revealed numerous tubular and interstitial brown DHA crystals, tubular degenerative changes and moderate to marked tubulointerstitial scarring. Two patients were initially misdiagnosed, one as primary hyperoxaluria and the other as chronic interstitial nephritis. All three patients progressed to ESRD, within 1 month following renal biopsy in two and after 9 months in one. All three patients underwent renal transplantation with early disease recurrence in three allografts in two patients.
  
  
  CONCLUSIONS
  DHA disease is an under-recognized condition that can lead to irreversible renal failure and frequently recurs in the transplant. It should be included in the differential diagnosis of crystalline nephropathy, even in the absence of history of nephrolithiasis.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. nasr.samih@mayo.edu
authors.forename: Samih H
authors.initials: SH
authors.lastname: Nasr
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Cornell
authors.forename: Dawn S
authors.initials: DS
authors.lastname: Milliner
authors.forename: Mark
authors.initials: M
authors.lastname: Boelkins
authors.forename: John
authors.initials: J
authors.lastname: Broviac
authors.forename: Mary E
authors.initials: ME
authors.lastname: Fidler
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000652:urine; D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics; D000328:Adult; D000493:Allopurinol / Q000627:therapeutic use; D003460:Crystallization; D003937:Diagnosis, Differential; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000175:diagnosis; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy / Q000652:urine*; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D014481:United States; D014545:Urinary Calculi / Q000737:chemistry / Q000175:diagnosis
chemical_list: C002993:2,8-dihydroxyadenine; D000493:Allopurinol; D000228:Adenine Phosphoribosyltransferase; D000225:Adenine