Kidney Week

Abstract: TH-PO718

Quantification of Urinary 2,8-Dihydroxyadenine Excretion in Patients with APRT Deficiency

Session Information

• Genetic Diseases of the Kidneys: Non-Cystic - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

• 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

• Runolfsdottir, Hrafnhildur L., Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland

Hrafnhildur L. Runolfsdottir,

• Palsson, Runolfur, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland

Runolfur Palsson,

• Thorsteinsdottir, Unnur A., University of Iceland, Reykjavik, Iceland

Unnur A. Thorsteinsdottir,

• Indridason, Olafur S., Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland

Olafur S. Indridason,

• Agustsdottir, Inger M., Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland

Inger M. Agustsdottir,

• Thorsteinsdottir, Margret, University of Iceland, Reykjavik, Iceland

Margret Thorsteinsdottir,

• Edvardsson, Vidar O., Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland

Vidar O. Edvardsson,

Group or Team Name

• The Rare Kidney Stone Consortium

Background

Adenine phosphoribosyltransferase deficiency (APRTd) is a rare disorder that results in renal excretion of 2,8-dihydroxyadenine (DHA) in large amounts, leading to kidney stones and chronic kidney disease. We have recently developed a high-throughput ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for quantification of urinary DHA. The purpose of this study was to assess 24-h urinary DHA excretion in APRTd patients, heterozygotes and healthy subjects, and the effect of varied purine intake in patients.

Methods

Nineteen patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, 4 heterozygotes and 10 healthy volunteers not taking medications affecting the metabolism or excretion of purines, participated in the study. The effect of varied dietary purine intake was assessed in 4 patients not receiving drug treatment. Urinary DHA excretion was measured in 24-h urine specimens and single void urine samples, expressed as mg/24 h and DHA/Cr ratio (mg/mmol), respectively. Associations were examined using Spearman‘s correlation coefficient.

Results

The median (range) urinary DHA excretion in 28 samples from 19 patients with APRTd was 138.1 (63.8-291.5) mg/24 h. No DHA was detected in any 24-h urine samples from 4 heterozygotes and 10 healthy individuals. The DHA/Cr ratio in 42 random void urine samples from 19 patients was 13.1 (3.8-37.2) mg/mmol. No correlation was found between urinary DHA excretion and kidney function (r=0.04, p=0.816). The correlation between the first morning void urine DHA/Cr and the 24-h urinary DHA excretion in samples obtained in the same 24-h period was high (r=0.84, p<0.001). The urine DHA excretion was 128.6 (107.2-160.1), 135.8 (114.4-188.4) and 133.5 (102.6-159.6) mg/24 h on self-selected, purine enriched and purine restricted diets, respectively.

Conclusion

Patients with APRTd excrete large amounts of DHA in their urine, while DHA is undetectable in both heterozygotes and healthy subjects. Timed urine samples can be replaced with DHA/Cr ratio in first morning void urine specimens for monitoring of DHA excretion. Short-term changes in purine intake do not seem to affect DHA excretion.

Funding

• NIDDK Support