Chronic kidney disease (CKD) is increasing in the U.S., particularly in older individuals. More than eightmillion people in the US have reduced kidney function. Even minor degrees of CKD attributed to hyper-tension and diabetes predict major cardiovascular risks, including death from myocardial infarction. Bothconditions are characterized by small vessel disease within the kidney. Atherosclerosis of the larger renalvessels can accelerate hypertension, is superimposed upon small vessel disease and produces renal injury. Renovascular disease both activates oxidative pathways and produces fibrosis. The regulation of thesepathways in human disease is poorly understood. BOLD (Blood Oxygen Level Dependent) magneticresonance (MR) provides a direct, non-invasive measure of deoxygenated hemoglobin. Experimental studiesindicate that BOLD MR levels relate directly to regional oxygen tension within kidney cortex and medulla.Our preliminary results indicate that deoxyhemoglobin changes measured by BOLD MR during blockade ofsodium reabsorption are related to levels of irreversible kidney dysfunction in atherosclerotic renovasculardisease. The overall hypothesis to be examined in these studies is that deoxygenated hemoglobin signals(the basis for BOLD magnetic resonance methodology), which reflect regional kidney ischemia, predictactivation of oxidative and fibrogenic pathways in kidneys with atherosclerotic vascular disease. We proposeto utilize these methods as a means of elucidating the pathogenesis and guiding therapy in humanatherosclerotic renovascular disease.
Our specific aims will examine the role of age, ethnicity and large-vessel renovascular disease underconditions that modify kidney oxygen consumption to examine their role in regulating injury pathways:
Aim No. 1 will examine the role of small vessel changes related to age and ethnicity to determine medullary andcortical changes in BOLD MR induced by furosemide and their relationship to regional blood flow (measuredby multi-detector CT), oxidative pathways and fibrogenic biomarkers.
Aim No. 2 will examine serial changesin medullary and cortical BOLD MR induced by furosemide in stenotic and non-stenotic kidneys afterchanging levels of oxygen consumption with endovascular revascularization.
Aim No. 3 will examine serialchanges in regional BOLD MR in stenotic and non-stenotic kidneys during systemic blood pressure reductionusing antihypertensive therapy without renalrevascularization. These projects will provide a critical extension into humans from the other studies of our program projectrelated to mechanisms of renovascular hypertension and injury (Romero), microvascular injury and repair(Lerman) and pathways of cell signaling in renal fibrogenic responses (Grande).
Showing the most recent 10 out of 128 publications