Urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency, carriers and healthy control subjects.
Chronic kidney disease
Crystalluria
Diagnosis of APRT deficiency
First-morning void urine samples
Kidney stones
Timed urine collections
UPLC-MS/MS assay
Journal
Molecular genetics and metabolism
ISSN: 1096-7206
Titre abrégé: Mol Genet Metab
Pays: United States
ID NLM: 9805456
Informations de publication
Date de publication:
Historique:
received:
25
03
2019
accepted:
25
05
2019
pubmed:
6
8
2019
medline:
1
5
2020
entrez:
6
8
2019
Statut:
ppublish
Résumé
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay. Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (r The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (r High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency.
Sections du résumé
BACKGROUND
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay.
METHODS
Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (r
RESULTS
The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (r
CONCLUSIONS
High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency.
Identifiants
pubmed: 31378568
pii: S1096-7192(19)30238-0
doi: 10.1016/j.ymgme.2019.05.015
pmc: PMC6864267
mid: NIHMS1536431
pii:
doi:
Substances chimiques
2,8-dihydroxyadenine
30377-37-8
Adenine Phosphoribosyltransferase
EC 2.4.2.7
Adenine
JAC85A2161
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
144-150Subventions
Organisme : NIDDK NIH HHS
ID : U54 DK083908
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
Adv Exp Med Biol. 1977;76B:304-11
pubmed: 857624
J Chromatogr A. 2000 Oct 13;894(1-2):157-64
pubmed: 11100858
Clin Chim Acta. 1996 Feb 9;245(1):85-92
pubmed: 8646818
Proc Natl Acad Sci U S A. 1985 May;82(9):2731-5
pubmed: 3921964
Clin Chem. 2005 Sep;51(9):1577-86
pubmed: 16020501
Heart Vessels. 2019 Jan;34(1):1-8
pubmed: 29936631
Diabetes Care. 2006 Apr;29(4):924-5
pubmed: 16567839
Am J Kidney Dis. 2016 Mar;67(3):431-8
pubmed: 26724837
Clin Chem. 1999 Dec;45(12):2086-93
pubmed: 10585670
J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Nov 15;1036-1037:170-177
pubmed: 27770717
Nephrol Dial Transplant. 1997;12 Suppl 2:6-9
pubmed: 9269691
Am J Kidney Dis. 2001 Sep;38(3):473-80
pubmed: 11532677
Nephrology (Carlton). 2018 Jan;23(1):5-11
pubmed: 29030945
Eur J Intern Med. 2018 Feb;48:75-79
pubmed: 29241594
Ann Intern Med. 2009 May 5;150(9):604-12
pubmed: 19414839
Gene. 1986;43(3):287-93
pubmed: 3527873
Clin Chem. 1987 Nov;33(11):2052-6
pubmed: 3677379
Clin Chem. 2006 Jun;52(6):1127-37
pubmed: 16613999
J Am Soc Nephrol. 2009 Mar;20(3):629-37
pubmed: 19158356
J Am Soc Nephrol. 2010 Apr;21(4):679-88
pubmed: 20150536