Quantitative Blood Oxygenation Level Dependent Magnetic Resonance Imaging for Estimating Intra-renal Oxygen Availability Demonstrates Kidneys Are Hypoxemic in Human CKD

Introduction: Kidney blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) has shown great promise in evaluating relative oxygen availability. This method is quite efficacious in eval-uating acute responses to physiological and pharmacologic maneuvers. Its outcome parameter, R2* is defined as the apparent spin-spin relaxation rate measured in the presence of magnetic susceptibility differences and it is measured using gradient echo MRI. Although associations between R2* and renal function decline have been described, it remains uncertain to what extent R2* is a true reflection of tissue oxygenation. This is primarily because of not taking into account the confounding factors, especially fractional blood volume (fBV) in tissue.Methods: This case-control study included 7 healthy controls and 6 patients with diabetes and chronic kidney disease (CKD). Using data before and after administration of ferumoxytol, a blood pool MRI contrast media, the fBVs in kidney cortex and medulla were measured.Results: This pilot study independently measured fBV in kidney cortex (0.23 +/- 0.03 vs. 0.17 +/- 0.03) and medulla (0.36 +/- 0.08 vs. 0.25 +/- 0.03) in a small number of healthy controls (n = 7) versus CKD (n = 6). These were then combined with BOLD MRI measurements to estimate oxygen saturation of hemoglobin (StO2) (0.87 +/- 0.03 vs. 0.72 +/- 0.10 in cortex; 0.82 +/- 0.05 vs. 0.72 +/- 0.06 in medulla) and partial pressure of oxygen in blood (bloodPO2) (55.4 +/- 6.5 vs. 38.4 +/- 7.6 mm Hg in cortex; 48.4 +/- 6.2 vs. 38.1 +/- 4.5 mm Hg in medulla) in control versus CKD. The results for the first time demonstrate that cortex is normoxemic in controls and moderately hypoxemic in CKD. In the medulla, it is mildly hypoxemic in controls and moderately hypoxemic in CKD. Whereas fBV, StO2, and bloodPO2 were strongly associated with estimated glomerular filtration rate (eGFR), R2* was not.Conclusion: Our results support the feasibility of quantitatively assessing oxygen availability using noninvasive quantitative BOLD MRI that could be translated to the clinic.