Urinary protein to creatinine ratio during the first month of life in very preterm infants-a prospective cohort study (PROTIPREMA)

Pediatr Nephrol. 2023 Mar;38(3):721-727. doi: 10.1007/s00467-022-05653-8. Epub 2022 Jun 27.


Background: Preterm infants have physiological proteinuria and values of urine protein to creatinine ratio (UPr/Cr) are higher compared to full-term infants during the first week of life. Few investigations explored the changes of proteinuria in very preterm infants (VPI, ≤ 31 weeks of gestation) older than a week, and it is unclear whether high and persistent proteinuria is associated with kidney injury in this population. This study aimed to (1) observe the changes of UPr/Cr during the first month of life in VPI and (2) describe clinical and biological variables associated with the changes of UPr/Cr.

Methods: Spot urine samples for UPr/Cr were collected on the first day of life (DOL1) and then on DOL2-3, DOL5-6, second week of life (WOL2), WOL3, and WOL4 in VPI cared for in a third-level NICU. We tested the relationship of UPr/Cr with perinatal variables and diseases.

Results: A total of 1140 urine samples were obtained for 190 infants. UPr/Cr values (mg/mmol) (median with interquartile) at DOL1, DOL2, DOL3, WOL2, WOL3, and WOL4 were, respectively, 191 (114-399), 226 (152-319), 225 (156-350), 282 (200-488), 308 (188-576), and 325 (175-664). At the multivariate analysis, lower gestational age (GA) and increasing postnatal age were the only variables significantly associated with higher UPr/Cr values (p < 0.001). There was wide intra- and interindividual variability in UPr/Cr, especially in infants with higher GA and clinical stability.

Conclusions: In VPI, UPr/Cr is higher at lower GA and increases with advancing postnatal age. High persistent proteinuria is not associated with clinical and biological variables reflecting kidney injury during the first month of life. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: AKI; Congenital nephron deficit; Creatinine; Extremely low birth weight; Hyperfiltration; IUGR; Proteinuria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / urine
  • Creatinine / urine
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Infant, Premature, Diseases*
  • Prospective Studies
  • Proteinuria / urine


  • Creatinine
  • Biomarkers