Early biomarkers of renal injury and protective effect of erythropoietin on kidneys of asphyxiated newborn rats

• Published in: Pediatric research Vol. 76; no. 1; pp. 11 - 16
• Main Authors: Stojanović, Vesna D., Vučković, Nada M., Barišić, Nenad A., Srdić, Biljana, Doronjski, Aleksandra D., Peco Antić, Amira E.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2014
• Subjects: 692/53; 692/699/1585/4; 692/699/1785; 692/700/1720/3186; Animals; Animals, Newborn; Asphyxia Neonatorum - drug therapy; Asphyxia Neonatorum - metabolism; Asphyxia Neonatorum - prevention & control; basic-science-investigation; Biomarkers - metabolism; Cell Adhesion Molecules - metabolism; Cystatin C - metabolism; Darbepoetin alfa; Erythropoietin - analogs & derivatives; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Female; Hypoxia; Kidney - drug effects; Kidney - pathology; Male; Medicine & Public Health; Pediatric Surgery; Pediatrics; Rats; Rats, Wistar; Time Factors; Treatment Outcome
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/pr.2014.50

Background:
The aims of this study were to determine which of the two biomarkers of renal injury, kidney injury molecule-1 or cystatin C, is more sensitive and to evaluate whether erythropoietin protects kidneys injured by perinatal asphyxia.
Methods:
Animals were split into three groups designated as follows: AE, pups that survived perinatal asphyxia and subsequently received 2.5 μg (0.1 ml) of darbepoetin-α (i.p.); A, the pups that survived perinatal asphyxia and received 0.1 ml of 0.9% NaCl; and C, control group. The pups were killed at different ages of life (6 h, 24 h, 48 h, 7 d, and 14 d of age; 10 rats in each subgroup). Immunohistopathological evaluation of kidneys was performed.
Results:
At 48 h and on days 7 and 14, absolute injury scores were significantly lower in group AE as measured by both biomarkers. Cystatin C expression was the most intensive 6 h after the hypoxic event (average value of absolute injury score was 2.82) and declined over time. Expression of kidney injury molecule-1 was less intensive, with the average value of absolute injury score being 2.02 at 6 h and 2.105 at 24 h; the peak value (2.155) was recorded 48 h after the hypoxic event.
Conclusion:
Erythropoietin has a protective effect on hypoxic kidneys. Cystatin C is more sensitive as an early biomarker of acute kidney injury in comparison with kidney injury molecule-1.