Abstract: SA-PO075

AKI Biomarkers and Cystic Fibrosis (CF): Does Having CF or Being a Girl Make a Difference?

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Quinlan, Cathy, The Royal Children's Hospital, Melbourne, New South Wales, Australia
  • Munro, Courtney B, Murdoch Childrens Research Institute, Melbourne, Victoria, New South Wales, Australia
Background

Novel urinary biomarkers are useful for prediction of acute kidney injury (AKI). Cystic fibrosis (CF) is a life limiting disease, caused by a gene defect in Cystic Fibrosis Transmembrane Regulator (CFTR), that predisposes the individual to recurrent respiratory infections which are often treated with nephrotoxic antibiotics. CFTR is highly expressed in the kidney, yet its effects in the human kidney in CF have not been closely examined. Previous studies have demonstrated renal glomerular hyperfiltration in children with CF. We set out to determine if novel urinary biomarkers could be used in children with CF, by determining reference levels in a paediatric CF population, and if this differed to healthy age-matched controls.

Methods

Urine was collected and analysed for kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL) and fibroblast growth factor-23 (FGF-23) using ELISA and normalised to urinary creatinine (UCr). Analysis of biomarkers by cohort (CF vs. healthy controls), age and sex was performed.

Results

Urine was collected on 448 occasions (CF n=229; healthy controls n=219) from children aged 1 to 6-years, median 4-years. Median values were: KIM-1 205.44 pg/mL (Interquartile range (IQR) 107.11 to 427.93), NGAL 1.03 ng/mL (IQR 0.01 to 3.65), FGF-23 45.25 pg/mL (IQR 17.05 to 96.21) and UCr 4.21 mmol/L (IQR 2.56 to 6.26). KIM-1, NGAL and UCr were higher in healthy controls than in CF (p=0.0000), suggesting a concentrating defect. FGF-23 was higher in CF (p=0.0101) which may reflect inflammation and infection. In healthy controls KIM-1 and UCr increased with age (p=0.0000), whereas NGAL decreased with age (p=0.0141). In CF, only UCr increased with age (p=0.0166). In healthy controls there were significant sex differences with KIM-1 and UCr higher for boys (p=0.0002 and p=0.0006), whereas NGAL was approximately 5 times higher for girls (p=0.0003). Sex differences were not observed in CF.

Conclusion

This is the first reference range study for urinary KIM-1, NGAL and FGF-23 in young children with CF and highlights significant differences in AKI biomarkers in CF, and for age and sex in healthy children. This information is essential for interpreting AKI biomarkers in the context of CF. Further research is required as to the role of CFTR in the kidney and why children with CF express not only lower biomarker levels, but the absence of sex differences.

Funding

  • Private Foundation Support