ROCHESTER, Minn. -- The National Heart, Lung and Blood Institute has awarded Mayo Clinic an $11 million, five-year grant for research designed to find new and improved ways to diagnose and treat kidney disease caused by atherosclerosis, the clogging, narrowing and hardening of arteries, specifically, one or both renal arteries. This is a condition that affects nearly 7 percent of people 65 years old and older.
Also called renal vascular disease, this particular condition is most commonly associated with hypertension and accounts for 5 percent to 10 percent of all hypertension cases (called secondary hypertension).
Kidney function is often used as a measure and indicator of coronary heart disease, which shares common risk factors with renal vascular disease: hypertension, diabetes and high blood cholesterol. A patient with renal vascular disease is at greater risk of morbidity or mortality associated with coronary heart disease, researchers say.
Why and how renal vascular disease occurs will be explored by an interdisciplinary group of Mayo Clinic researchers led by J. Carlos Romero, M.D., a specialist in physiology and biomedical engineering, who has conducted research in this area for more than two decades. There will be four studies which will involve specialists in physiology and biomedical engineering, nephrology and hypertension, cardiovascular diseases, renal pathophysiology, transplantation biology, radiology and vascular interventional radiology.
“We will show how the disease is complicated by atherosclerosis, and we will attempt to determine the best way to apply our findings to humans,” says Dr. Romero, adding that the study reaffirms Mayo Clinic’s commitment to translational research, the clinical application of scientific medical research.
Researchers will apply basic science research findings to patients to assess the effectiveness of treatments that include renal angioplasties, high blood pressure medication and a procedure that involves regenerating damaged cells.
Patients diagnosed with renal vascular disease often have a narrowed artery or an obstruction in one or both renal arteries. Medication used to control high blood pressure is sometimes prescribed. Or, to restore blood flow to the kidneys, doctors might perform an angioplasty in which a stent is placed in the artery. Unfortunately, few patients actually improve after the procedure, yet about $350 million is spent annually in the United States on angioplasties of renal arteries — a procedure which is becoming more common, says Lilach Lerman , M.D ., Ph.D., the research program’s co-director.
For other patients, she says, their condition does not improve or it even deteriorates after the procedure. One Mayo Clinic study showed that of 304 renal angioplasties performed, kidney function improved in 27 percent of patients after the procedure, it failed to improve in 53 percent of patients and in 21 percent of cases, kidney function deteriorated after the procedure.
Because of the aging population in the United States, it is critical to support research that will enable physicians to predict the onset of renal vascular disease, diagnose it early and evaluate how it affects the kidneys, Dr. Lerman says.
“There is a very pressing need to find the mechanisms involved in impairing renal function. We will investigate renal vascular disease using sensitive imaging tools to elucidate its underlying mechanisms and in doing so, we hope the discoveries we make will lead to the early prediction, detection and evaluation of this disease,” she says.
“Understanding these processes will indicate to us what treatment should be developed and used in the early stages of the disease to prevent renal deterioration,” Dr. Romero says.
A key part of this grant is to develop and employ novel imaging tools to study renal vascular disease. New medical imaging technologies, such as a 64-slice multi-detector CT scan, will be used to assess kidney function. This new technology produces three-dimensional images with high spatial and temporal resolution in a way that can provide more insight into the anatomy and physiology of kidneys than ever before possible.
“Normally it is very difficult to provide quantitative measures of each kidney function, but the multi-detector CT scan can provide this very important data on the status of renal function,” Dr. Lerman says.
In addition, researchers will apply a new technique of blood oxygen level-dependent MRI (BOLD MRI). This imaging technology will be used to measure the level of deoxyhemoglobin in the kidneys (a form of hemoglobin without oxygen) to determine how hard the kidneys are working. The harder the kidneys work, the more oxygen they use.
The new research projects include:
- “Markers of Renal Damage in Renovascular Hypertension,” with Dr. Romero as the project lead. This study, which will be in animal models, will focus on the role and effect of kidney damage in response to renal angioplasty or other medical treatment. This study will have an impact on the diagnosis, follow up and treatment of patients with renal vascular hypertension.
- “Renal Microvascular Damage and Repair in Atherosclerotic Renovascular Disease,” with Dr. Lerman as the project lead. This study will test the hypothesis that atherosclerosis contributes to irreversible kidney damage by amplifying oxidative stress, which instigates endothelial and epithelial cell injury, impairs cellular repair and aggravates kidney damage while impairing its recovery.
- “Signaling Pathways in Renovascular Hypertension,” with Joseph Grande , M.D ., Ph.D ., as the project lead. This study, which will be conducted in mice models, will focus on the correlation between the structural changes of cells and cellular signaling as possibilities for new drug targets for renal hypertension.
- “Tissue Oxygenation in Human Renovascular Disease,” with Stephen Textor, M.D ., as the project lead. This study will combine the knowledge and information gained in the first three studies for application to patient care.
Project co-investigators include Amir Lerman , M.D .; Karl Nath , M.D .; Jeffrey Platt , M.D .; James Glockner , M.D .; Michael McKusick , M.D .; Erik Ritman , M.D ., Ph.D .; and Sanjay Misra , M.D .
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