Acute kidney injury: arterial spin labeling to monitor renal perfusion impairment in mice-comparison with histopathologic results and renal function

Purpose: To determine if arterial spin-labeling (ASL) magnetic resonance (MR) imaging can show serial changes in renal perfusion in mice with ischemia-induced acute kidney injury (AKI) and to compare imaging results with those of renal histologic examination and inulin and para-aminohippuric acid (PAH) clearance.

Materials and methods: In this animal care committee-approved study, AKI was induced in C57Bl/6 mice (n = 26) by clamping the right renal pedicle for 35 minutes for moderate (n = 16) or 45 minutes (n = 11) for severe AKI. Renal perfusion was measured in 10 animals with moderate and seven animals with severe AKI before and at five time points 1-28 days after surgery by using ASL with a 7-T MR imaging unit. Kidney volume loss and histologic evidence of acute tubular injury were assessed. Inulin and PAH clearance was determined in four animals with moderate and six animals with severe AKI to evaluate renal function and plasma flow for statistical analysis. Repeated measures analysis of variance, unpaired t tests, and correlation analysis were used.

Results: Renal perfusion values at day 7 were significantly reduced after moderate (56% ± 8; P < .01) and severe (33% ± 6; P < .001) AKI compared with presurgery values. Renal perfusion had returned to baseline levels at day 21 after moderate (96% ± 14) and remained compromised until day 28 after severe (46 % ± 9; P < .05) AKI. At day 28, for moderate versus severe AKI, kidney volume (84% ± 6 vs 60% ± 5; P < .05), degree of tubular injury (5.6% ± 1.8 vs 15.8% ± 2.4; P < .01), and inulin and para-aminohippuric acid clearance (47.5 µL/min ± 5.6 vs 7.3 µL/min ± 2.7; P < .001 and 100.8 µL/min ± 24.3 vs 4.8 µL/min ± 1.0; P < .001, respectively) were significantly different. Relative renal perfusion at days 7-28 significantly correlated with kidney volume loss (P < .01) and tubular injury (P < .05) 4 weeks after AKI.

Conclusion: ASL allows evaluation of renal perfusion impairment associated with kidney volume loss and histologic changes after AKI in mice and may serve as a noninvasive biomarker for AKI.