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, < 3 × 10 and 7.2 × 10, respectively), and the ratios orotic acid/crn, uracil/crn, and carbamyl-β-alanine/crn (p = 0.03, 1.4 × 10 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.

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http://dx.doi.org/10.1016/j.ymgme.2023.107649DOI Listing

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