Abstract
Background
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).
Methods
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 (Nglom) and apparent glomerular volume (aVglom) were determined. CF toxicity was assessed at two and 28 days in healthy rabbits.
Results
Nglom was lower in the AKI group as compared to controls (74,034 vs 198,722, p < 0.01). aVglom was not different (AKI: 7.3 × 10−4 vs control: 6.2 × 10−4 mm3, p = 0.69). AKI kidneys had a band of glomeruli distributed radially in the cortex that were undetectable by MRI. Following CF injection, there was no difference in body or organ weights except for the liver, and transient changes in serum iron, platelets and white blood cell count.
Conclusions
Brief nephrotoxin exposure during nephrogenesis results in fewer glomeruli and glomerular maldevelopment in a unique pattern detectable by MRI. Whole kidney evaluation by CFE-MRI may provide an important tool to understand the development of CKD following AKI.
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Acknowledgements
We thank Molecular Imaging Core (Rene “Jack” Roy), Advanced Microscopy Core, and ACUC (Sanford Feldman, Gina Wimer, and Jeremy Gatesman). This work was supported by The Hartwell Foundation and NIH/NIDDK: R01DK110622 and R01DK111861. This work used the Bruker ClinScan 7 T MRI in the Molecular Imaging Core, which was purchased with support from NIH grant 1S10RR019911-01 and is supported by the University of Virginia School of Medicine.
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J.R.C. and K.M.B.: designed the study and drafted and revised the paper; J.R.C., E.J.B., K.d., S.C., D.H., S.N., V.P.: carried out experiments; J.R.C., E.J.B., H.C., N.P.C., K.M.B.: analyzed the data; and all authors approved the final version of the manuscript.
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J.R.C. and K.M.B. are co-owners of Sindri Technologies, LLC.
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Charlton, J.R., Baldelomar, E.J., deRonde, K.A. et al. Nephron loss detected by MRI following neonatal acute kidney injury in rabbits. Pediatr Res 87, 1185–1192 (2020). https://doi.org/10.1038/s41390-019-0684-1
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DOI: https://doi.org/10.1038/s41390-019-0684-1
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