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


CONCLUSIONS
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.
1] Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia [2] Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia.
Vesna D
VD
Stojanović
1] Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia [2] Clinical Centre of Vojvodina, Centre for Pathology and Histology, Novi Sad, Serbia.
Nada M
NM
Vučković
1] Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia [2] Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia.
Nenad A
NA
Barišić
Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Biljana
B
Srdić
1] Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia [2] Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia.
Aleksandra D
AD
Doronjski
1] Department of Nephrology, University Children's Hospital, Belgrade, Serbia [2] Medical School, University of Belgrade, Belgrade, Serbia.
Amira E
AE
Peco Antić
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D055316:Cystatin C / Q000378:metabolism*; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000860:Hypoxia; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D055316:Cystatin C; D000068256:Darbepoetin alfa; D004921:Erythropoietin; C110936:Havcr1 protein, rat