Noninvasive Quantification of Renal Oxygen Utilization in Early Kidney Disease

点击翻译按钮获取中文摘要

Project Summary/Abstract (30 lines): Chronic kidney disease (CKD) is characterized by a progressive loss of kidney function and is a major risk factor for adverse cardiovascular outcomes. It is estimated that CKD affects 15% of US adults. Current measures of kidney function rely on equations to calculate an estimated glomerular filtration rate (eGFR), require multiple blood and urine samples, or detect dysfunction after irreversible damage may already have occurred. These limitations highlight an unmet need for a better biomarker that can detect kidney dysfunction earlier. Renal metabolic rate of oxygen (MRO2) is a suitable metric because it directly represents renal function and workload. Moreover, renal MRO2 has been found to increase during the early stages of diabetic kidney disease. MRO2 can be quantified with magnetic resonance imaging oximetry, including susceptometry-based oximetry (SBO) or T2- based oximetry (T2O). However, SBO is not appropriate for kidney imaging because of restrictions on vessel orientation and lack of adjacent tissue for reference phase measurement. T2O is the preferred option, but current T2-based methods only measure venous oxygen saturation (SvO2) and require a separate measurement of blood flow velocity to quantify MRO2. The proposed research introduces a noninvasive T2-based oximetry method to quantify whole-organ renal MRO2 by simultaneously measuring SvO2 and blood flow velocity in an interleaved manner, thereby overcoming the limitations of other T2-based methods. The central hypothesis of the proposed research is that renal MRO2 has the potential to serve as a direct, quantitative marker of kidney function and enable earlier detection of diabetic CKD. To fulfill this objective and test the central hypothesis, the following specific aims will be pursued: (1A) Develop the MRI oximetry pulse sequence and test in phantoms to assess accuracy of measured parameters. (1B) Implement the pulse sequence to quantify SvO2 in the superior sagittal sinus of the brain and whole-brain cerebral MRO2. Initial studies will quantify whole-brain MRO2 because of minimal physiologic and voluntary motion, and availability of established data to compare with. (2A) Design and implement the pulse sequence for kidney imaging to quantify renal MRO2, and test the performance of the method with an oral diuretic. (2B) Quantify renal MRO2 and calculate eGFR in prediabetic and diabetic patients to evaluate the hypothesis that renal MRO2 can serve as an early marker of kidney dysfunction. The proposed research to quantify renal MRO2 introduces a method to noninvasively quantify renal MRO2 with potential applications as an accurate marker of early-stage kidney disease and for monitoring response to intervention.