Summary:
Objective: The study of histological changes of the kidneys and the application
of metabolomics in an experimental model of neonatal normocapnic hypoxia and
reoxygenation in newborn piglets.
Materials and Methods: In this experimental model, normocapnic hypoxemia was
induced in 40 male, newborn Landrace/Large-White piglets. When bradycardia (HR
< 60) or severe hypotension (MAP < 15 mmHg) occurred, reoxygenation was
initiated. Animals were allocated in 4 groups according to the oxygen
concentration they were resuscitated with: group 1, 2, 3, 4 received 18%, 21%,
40%, 100% O2, respectively. In addition, 4 piglets who did not suffered hypoxia
were studied and served as control group. Upon histological examination,
hematoxylin, eosin and PAS - stained renal sections were observed at the
optical microscope. Moreover, metabolomic analysis of urine by NMR spectroscopy
occurred.
Results: In the kidneys of the control group were observed tubule - glomerular
nodules as evidence of active glomerulogenesis. Kidneys suffered hypoxia showed
tubular casts (95%), tubular dilatation (87.5%), tubular vacuolization (70%),
eosinophilia (52.5%), fragmentation of the brush border (50%), sloughing (50%),
edema (32.5%) and apoptosis (15%). In metabolomics urinalysis were significant
differences in metabolomic profiles between animals with and without asystole
as well as those who died and those who did not have asystole and recovered
quickly. Furthermore, significant changes occurred in metabolomic urinary
profile of piglets who resuscitated with different oxygen concentrations.
Conclusions: Hypoxia appears to cause early histological changes in the
kidneys, especially in renal tubules. The vacuolation of proximal and distal
tubules and dilatation of distal tubules were the main histological changes
after hypoxia - reoxygenation. Instead, tubular casts seem not to be a specific
finding of kidney damage. Also, the outcome of resuscitation depented on the
initial metabolic profile of piglets. Therefore, the discovery of new
biomarkers of acute kidney injury and the study of the metabolic profile before
hypoxia lead to timely and individualized diagnosis and intervention and as a
result better prognosis.
Keywords:
Kidneys, Injury, Metabolomics, Hypoxia, Reoxygenation
