Impact of renal impairment, hepatic function, and circadian rhythm on pre-treatment plasma uracil levels.

AIM: To determine the five-year incidence of hyperuracilemia (plasma uracil (P-uracil) ≥ 16 ng/mL) and its association with renal and hepatic function. Furthermore, to characterize circadian variation in P-uracil. METHODS: All adult patients (≥18 years) in the Central Denmark Region with a P-uracil measurement performed at the Department of Clinical Biochemistry, Aarhus University Hospital, between September 2021 and December 2025 were included. Measurements of estimated glomerular filtration rate (eGFR), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin were also extracted. Circadian variation was assessed from sampling time using hourly medians and interquartile ranges (IQRs). RESULTS: The median P-uracil of 3728 patients was 8.0 ng/mL (IQR 7.24 to 11.40 ng/mL). A subcohort of 3361 patients with concurrent measurements of eGFR and liver function tests was included in multivariate analyses, where male sex (+6.72%, p < 0.001) and ALP (+3.16% per times the upper normal limit of the reference interval, p < 0.001) were positively, and eGFR (--0.61% per eGFR point, p < 0.001) inversely, associated with P-uracil; logistic regression confirmed these associations (odds ratio of 1.71, 1.25, and 0.96, respectively). No circadian variation in P-uracil was visually apparent. CONCLUSION: This study demonstrated a consistent and independent association between impaired renal function and elevated P-uracil. Associations with liver function tests were less consistent, with only ALP showing an independent relationship in multivariable analyses. No evidence of clinically relevant circadian rhythm in P-uracil was observed.