Renal function, sex and age influence purines and pyrimidines in urine and could lead to diagnostic misinterpretation

Cathrin Lytomt Salvador; Per Trygge Kjelland Flemmen; Camilla Tøndel; Yngve Thomas Bliksrud; Ellen Fun Fong Tsui; Atle Brun; Anna Bjerre; Lars Mørkrid

doi:10.1016/j.ymgme.2023.107649

Renal function, sex and age influence purines and pyrimidines in urine and could lead to diagnostic misinterpretation

Mol Genet Metab. 2023 Nov;140(3):107649. doi: 10.1016/j.ymgme.2023.107649. Epub 2023 Jul 5.

Authors

Cathrin Lytomt Salvador¹, Per Trygge Kjelland Flemmen², Camilla Tøndel³, Yngve Thomas Bliksrud², Ellen Fun Fong Tsui², Atle Brun⁴, Anna Bjerre⁵, Lars Mørkrid⁶

Affiliations

¹ Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. Electronic address: catsal@ous-hf.no.
² Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
³ Department of Pediatrics, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
⁴ Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
⁵ Department of Pediatrics, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁶ Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

PMID: 37517327
DOI: 10.1016/j.ymgme.2023.107649

Abstract

Glomerular filtration rate (GFR) is commonly used in clinical practice for the diagnosis and follow-up of chronic kidney disease. Screening for inborn errors of metabolism (IEM) is based on analysis of biomarkers in urine, reported by their ratio to urinary creatinine (crn). Impaired renal function may complicate the interpretation of several biomarkers used for screening of IEM. Our goal was to investigate the influence of kidney function, in terms of measured GFR (mGFR) on purines and pyrimidines in urine, in addition to the relationship to sex, age, pH and ketosis. Children (n = 96) with chronic kidney disease (CKD), in different CKD stages, were included. Urine samples were obtained prior to the injection of iohexol. Serum samples at 7 time-points were used to calculate mGFR based on iohexol plasma clearance. The association with sex, age, ketosis and pH was examined in samples of the laboratory production from 2015 to 2021 (n = 8192). Age was a highly significant covariate for all markers. GFR correlated positively to several purines and pyrimidines; the ratios hypoxanthine/crn, xanthine/crn and urate/crn (p = 2.0 × 10^-14, < 3 × 10^-15 and 7.2 × 10^-4, respectively), and the ratios orotic acid/crn, uracil/crn, and carbamyl-β-alanine/crn (p = 0.03, 1.4 × 10^-6 and 0.003, respectively). The values of urate/crn, xanthine/crn, uracil/crn, and carbamyl-β-alanine/crn were higher in females above 16 years of age. Ketosis and pH influenced some markers. In conclusion, decreased renal function interferes with the excretion of urinary purines and pyrimidines, and this could change decision limits substantially, e.g. result in false negative results in Lesch-Nyhan syndrome. SYNOPSIS: GFR influences purines and pyrimidines in urine. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.

Keywords: Children; Chronic renal insufficiency; Glomerular filtration rate; Lesch-Nyhan; Purines; Pyrimidines; Urate.

Publication types

Clinical Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Biomarkers
Child
Creatinine / metabolism
Female
Humans
Iohexol / metabolism
Ketosis*
Kidney / metabolism
Male
Purines
Pyrimidines
Renal Insufficiency, Chronic* / diagnosis
Uracil
Uric Acid
beta-Alanine

Substances

beta-Alanine
Biomarkers
Creatinine
Iohexol
Purines
Pyrimidines
Uracil
Uric Acid

Associated data

ClinicalTrials.gov/NCT01092260