Nephron loss detected by MRI following neonatal acute kidney injury in rabbits.
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ABSTRACT:
SUBMITTER: Charlton JR
PROVIDER: S-EPMC7255918 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Nephron loss detected by MRI following neonatal acute kidney injury in rabbits.
Charlton Jennifer R JR Baldelomar Edwin J EJ deRonde Kimberly A KA Cathro Helen P HP Charlton Nathan P NP Criswell Stacey J SJ Hyatt Dylan M DM Nam Sejin S Pearl Valeria V Bennett Kevin M KM
Pediatric research 20191205 7
<h4>Background</h4>Acute kidney injury affects nearly 30% of preterm neonates in the intensive care unit. We aimed to determine whether nephrotoxin-induced AKI disrupted renal development assessed by imaging (CFE-MRI).<h4>Methods</h4>Neonatal New Zealand rabbits received indomethacin and gentamicin (AKI) or saline (control) for four days followed by cationic ferritin (CF) at six weeks. Ex vivo images were acquired using a gradient echo pulse sequence on 7 T MRI. Glomerular number (N<sub>glom</su ...[more]
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Project description:BackgroundClinical studies suggest that female sex plays a protective role in the development and progression of kidney disease. Recent experimental studies indicate that in male rats early nephron loss under ongoing nephrogenesis is accompanied by severe long-term sequelae. In humans, nephron formation occurs mainly in the third trimester, ceasing with 36 weeks of gestation. Due to perinatal complications, preterm infants delivered during this vulnerable period may undergo acute nephron loss. In rats nephrogenesis persists until postnatal day 10, reflecting the situation of human preterms with persisting nephrogenesis. In our animal model of neonatal uninephrectomy, female and male rats were uninephrectomized at day 1 of life. Hypothesizing sex-dependent differences, long-term renal outcome was assessed after 1 year.ResultsIn both sexes, neonatal uninephrectomy was not followed by arterial hypertension at 1 year of age. Compensatory weight gain and glomerular hypertrophy of the remaining kidney occurred in uninephrectomized female and male animals. Selected markers of interstitial inflammation and fibrosis were regulated sex-dependently. The expression of monocyte chemoattractant protein-1 was increased in females, while tubulointerstitial infiltration by M1 macrophages was significantly higher in males after neonatal uninephrectomy. Neonatally uninephrectomized male rats had more glomerulosclerosis and podocyte damage compared to females, which was assessed by a semiquantitative score and desmin staining. RT-PCR revealed that after neonatal uninephrectomy in the remaining contralateral kidney of female rats the expression of candidate genes of renal development and function, i.e., wt-1, nephrin, synaptopodin, gdnf, and itga8 was higher than in males.ConclusionsBased on these observations we conclude that female sex is protective in the long-term response of the kidney to acute nephron loss under active nephrogenesis.
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Project description:Acute kidney injury (AKI) is an important risk factor for chronic kidney disease (CKD), but the underlying mechanisms of failed tubule repair and AKI-CKD transition are incompletely understood. In this study, we aimed for dynamic tracking of tubule injury and remodeling to understand if focal injury upon AKI may spread over time. Here, we present a model of AKI, in which we rendered only half of the kidney ischemic. Using serial intravital 2-photon microscopy and genetic identification of cycling cells, we tracked dynamic tissue remodeling in post- and non-ischemic kidney regions simultaneously and over 3 weeks. Spatial and temporal analysis of cycling cells relative to initial necrotic cell death demonstrated pronounced injury propagation and expansion into non-necrotic tissue regions, which predicted tubule atrophy with epithelial VCAM1 expression. In summary, our longitudinal analyses of tubule injury, remodeling, and fate provide important insights into AKI pathology.
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2021-06-09 | GSE176395 | GEO
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