MRI-Based Renal Oximetry in Early Diabetic Kidney Disease

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PROJECT SUMMARY Chronic kidney disease (CKD), affecting 15% of US adults, is characterized by a progressive loss of kidney function. The leading cause of CKD is type-2 diabetes mellitus, and up to 40% of type-2 diabetic patients go on to develop CKD. Current measures of kidney function are limited in that they estimate glomerular filtration rate (eGFR), require multiple blood and urine samples over several hours, or detect disease after irreversible damage has already occurred. Thus, there is a need for a better biomarker that can detect kidney dysfunction earlier. Renal metabolic rate of oxygen (MRO2) is a suitable metric that directly represents kidney function. In animal models MRO2 has been found to increase during the early stages of diabetic kidney disease. Magnetic resonance imaging (MRI) oximetric techniques can noninvasively quantify MRO2. A widely used method for quantifying MRO2 of the brain measures blood water transverse relaxation time T2 in a draining vein and converting the result via a calibration curve to venous oxygen saturation (SvO2), in addition to a separate scan to acquire blood flow velocity, which are the key physiological parameters needed to quantify MRO2 via Fick’s principle. The proposed research introduces a new T2-based oximetry method that overcomes the limitations of prior T2-based methods by simultaneously measuring SvO2 and blood flow velocity in a single 18-second breath-hold period. The novel interleaving strategy underlying the proposed technique enables quantification of MRO2 in a single pass. The hypothesis of the proposed research is that renal MRO2 will serve as a direct, quantitative marker of early kidney disease before progression to irreversible organ dysfunction. To test this hypothesis, the following specific aims will be pursued: (1) Optimize the T2-based oximetry pulse sequence and quantify cerebral MRO2 to test its performance against well-established MRI oximetry methods. Initial studies will be performed in the brain because of minimal physiologic motion and availability of data for comparison. (2): Transfer the method to the abdomen and quantify renal MRO2 in healthy human subjects and evaluate the method’s precision. (3): Perform a pilot study to assess renal MRO2 as a marker of early-stage diabetic kidney disease through quantification of renal MRO2, eGFR, and microalbuminuria in prediabetic and type-2 diabetic patients in comparison to healthy reference subjects. The method is projected to yield insights into renal metabolism during the early stages of kidney disease and may eventually provide a means for monitoring patients with diabetic kidney disease during treatment.