M SUTHERLAND1, A SHAH2,3, I HANCHAPOLA3, C HUANG3, R SCHITTENHELM3, M BLACK1
1Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia, 2Monash Bioinformatics Platform, Monash University, Clayton, Australia, 3Monash Biomedical Proteomics Facility, Monash University, Clayton, Australia
Aim: To determine the impact of gestational age on the urinary proteome of preterm infants, and identify candidate biomarkers of renal dysfunction/injury.
Background: Preterm infants (born <37 weeks gestation) are highly susceptible to acute kidney injury (AKI). Serum creatinine and urine output, currently used in the diagnosis of AKI in infants, are both late-onset and non-specific markers that can also be influenced by renal functional maturity. As yet, no AKI diagnostic criteria have been developed specifically for preterm infants. Early diagnosis, enabling immediate intervention, is key to mitigating the adverse impact of neonatal AKI on long-term renal health. Therefore, there is a critical need to identify specific AKI biomarkers (independent of renal maturity) that can be assessed non-invasively in this vulnerable population.
Methods: Spot urine samples were collected from 30 preterm infants (born 24-35 weeks gestation) at postnatal day 7. Global protein quantification was performed using nano-LC-ESI DIA mass spectrometry. Linear regression models were used to determine the associations between individual protein levels, gestational age, and measures of renal function (eg. serum creatinine, fractional excretion of sodium (FENa), and pathological proteinuria (≥ 500mg/L)).
Results: A total of 1,255 urinary proteins were quantified across the samples. Of these, 283 (23%) were significantly correlated with gestational age at birth, including some known indicators of glomerular (neprilysin, podocalyxin) and tubular (cystatin C, cubilin) injury. After correcting for gestational age, proteins most strongly correlated with renal function parameters (p<0.0001) included PPGB (serum creatinine: r²=0.598), CSTN1 (FENa: r²=0.744), and AATC (proteinuria: r²=0.677).
Conclusions: Gestational age at birth significantly impacts the early postnatal urinary proteome of preterm infants. Longitudinal studies are now required to assess the utility of candidate biomarkers.
Dr. Megan Sutherland is a NHMRC CJ Martin Early Career Research Fellow at the Biomedicine Discovery Institute, Department of Developmental Biology, Monash University. Her research is focused on understanding the impact of preterm birth on renal development and function.