Evaluation of intra-renal oxygenation in db/db mice by BOLD MRI

Diabetes promotes chronic renal hypoxia, which is a pathway leading to end stage renal disease (ESRD) [J Am Soc Nephrol 17: 17–25, 2006]. Among the many techniques available to evaluate intra-renal oxygenation, blood oxygen level-dependent (BOLD) MR imaging is currently the only non-invasive method that can be readily used in vivo in both animal models and humans [Nephron Clin Pract 2006; 103: c58-65]. BOLD MRI studies in streptozotocin (STZ)-induced rat model of Type I diabetes have shown increased levels of medullary hypoxia at very early time points following STZ administration [Invest Radiol 2007; 42: 157-162; J Magn Reson Imaging 2003; 17: 104-13]. A commonly used mouse model to investigate diabetic kidney disease is the db/db mouse [Am J Physiol Renal Physiol 2003; 284: F1138-44]. These transgenic mice are homozygous for the db gene and show signs of diabetes as early as 4-6 weeks of age [Am J Pathol 1972; 66: 193-224]. Their littermates (db/m), on the other hand, are completely normal. These mice have a mutation in the LepR gene, which leads to obesity and diabetes [Am J Physiol Regul Integr Comp Physiol 2000; 278: R320-330]. The progression of diabetes in mice mirrors that in humans [Am J Physiol Renal Physiol 2003; 284: F1138-1144; Am J Pathol 2005; 167: 327-336]. In this study, we used BOLD MRI technique to evaluate renal medullary oxygenation levels in db/db mice compared to their littermates db/m mice. Based on our previous findings in the Type I diabetes rat model, we hypothesized that db/db mice will show enhanced medullary hypoxia compared to their control db/m mice.