Abstract: SA-PO649
Clinical Utility of a Novel Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) Plasma 2,8-Dihydroxyadenine Assay in Patients with Adenine Phosphoribosyltransferase (APRT) Deficiency
Session Information
- Genetic Kidney Diseases: Models, Mechanisms, and Therapies
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Thorsteinsdottir, Unnur A., Heilbrigdisvisindasvid - Haskoli Island, Reykjavik, Iceland
- Runolfsdottir, Hrafnhildur L., Landspitali, Reykjavik, Capital, Iceland
- Eiriksson, Finnur Freyr, Heilbrigdisvisindasvid - Haskoli Island, Reykjavik, Iceland
- Edvardsson, Vidar O., Landspitali, Reykjavik, Iceland
- Thorsteinsdottir, Margret, Heilbrigdisvisindasvid - Haskoli Island, Reykjavik, Iceland
- Palsson, Runolfur, Landspitali, Reykjavik, Iceland
Background
Treatment with a xanthine oxidoreductase inhibitor (XORi), allopurinol or febuxostat, reduces urinary 2,8-dihydroxyadenine (DHA) excretion and slows CKD progression in adenine phosphoribosyltransferase deficiency (APRTd). We have developed and validated an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) plasma assay for the simultaneous quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in human plasma. The aims of the current study were to assess the clinical applicability of the assay.
Methods
DHA, allopurinol, oxypurinol and febuxostat were quantified in 82 bio-banked plasma samples using the novel assay. Clinical patient data were obtained from our APRT Deficiency Patient Registry. Plasma DHA concentration was correlated with age, sex, XORi treatment status and estimated glomerular filtration rate (eGFR).
Results
The average plasma concentration was 323 ng/mL for DHA and 292 ng/mL for adenine in untreated (n=28) APRTd patients. When treated with allopurinol 400 mg/day (n= 29) or febuxostat 80 mg/day (n=25), the average concentration of DHA was 61 ng/mL and below the limit of quantification, respectively, and of adenine 818 and 1264 ng/mL, respectively. DHA was not detected in plasma samples from controls (n=9). The average plasma concentration of allopurinol, oxypurinol and febuxostat in patients receiving XORi therapy was 1695 ng/mL, 11612 ng/mL and 313 ng/mL, respectively. There was a moderate negative correlation between the plasma DHA concentration and eGFR in untreated patients. No significant correlation was found between age and sex and the DHA plasma concentration.
Conclusion
The UPLC-MS/MS plasma assay for quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in human plasma can be used for therapeutic monitoring in APRTd. Measurement of plasma DHA will also be a useful test for the diagnosis of APRTd.
Funding
- Government Support – Non-U.S.