Nephron loss detected by MRI following neonatal acute kidney injury in rabbits

BACKGROUND: Acute kidney injury affects nearly 30% of preterm neonates in the intensive care unit. We aimed to determine if 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 7T MRI. Glomerular number (N(glom)) and apparent glomerular volume (aV(glom)) were determined. CF toxicity was assessed at 2 and 28 days in healthy rabbits. RESULTS: N(glom) was lower in the AKI group as compared to controls (74,034 vs 198,722, p<0.01). aV(glom) was not different (AKI:7.3 ×10(−4) vs. control: 6.2 ×10(−4) mm(3), 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.