Role of functional magnetic resonance imaging in evaluating renal hypoxic injury in mice with lupus nephritis

Abstract

Objective To investigate the utility of diffusion weighted imaging (DWI) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in the assessment of renal hypoxia in an experimental model of mice with lupus nephritis (LN). Methods MRL/lpr mice (n=13) were studied and C57BL/6 mice (n=10) served as controls. Urinary albumin to creatinine ratio (ACR), serum creatinine (Scr), anti-ds-DNA antibody, and complement C3 levels were measured. The mice underwent coronal echo-planar DWI and BOLD MRI of the kidneys when they were 14-16 weeks old. Hypoxyprobe was administered intraperitoneally to the mice 1 hour before they were sacrificed. The distribution of HypoxyprobeTM-1, hypoxia-inducible factor 1α (HIF-1α) and heme oxygenase-1 (HO-1) in renal tissues was detected by immunohistochemical analysis and Western blotting. Results Urinary ACR, Scr and anti-ds-DNA antibody levels in MRL/lpr mice were significantly higher than that in C57BL/6 mice. It was found that HypoxyprobeTM-1, HIF-1α and HO-1 distributed widely in the renal tissue of MRL/lpr mice, and closely associated with the renal tubulointerstitial lesion. The mean apparent diffusion coefficient (ADC) value of kidneys in MRL/lpr mice was (1.52±0.27) ×10-3 mm2/s, and the mean R2* values of the renal cortex and medulla were (30.95±4.59)/s and (23.43±3.06)/s respectively, all significantly lower than that in C57BL/6 mice (P=0.037, P=0.030 and P=0.043, respectively). The ADC of medulla was negatively correlated with urinary albumin to creatinine ratio (r=-0.364, P=0.032; r=-0.329, P=0.050), the ADC of cortex was negatively correlated with the level of serum creatinine (r=-0.814, P=0.014; r=-0.755, P=0.031) when b value was 500 s/mm2 and 800 s/mm2, and the mean R2* value was negatively correlated with the degree of tubulointerstitial lesions and the expression of hypoxia parameters (all P<0.05). Conclusions Renal hypoxia may play an important role in renal tubulointerstitial lesion. Functional MRI may be used to monitor renal function changes, pathological injuries and renal hypoxia in LN. Key words: Magnetic resonance imaging; Lupus nephritis; Anoxia; Renal tubulointerstitial lesion