Patients with chronic kidney disease have a 20 to 30-fold higher risk of cardiovascular mortality than the general population, and are at higher risk for vascular problems. In addition, although patients with CKD represent only a small fraction of Medicare patients, the financial burden amounts to nearly one-fourth of annual expenditures. The costs for treating patients with chronic and end stage renal disease rose to $32 billion last year, indicating a critical need for more research.
Researchers at New York Medical College are exploring new treatments and diagnostic strategies for kidney disease. Chronic and end stage kidney disease, dialysis, links to diabetes and cancer, as well as transplant issues, are among the vital areas under scrutiny.
Among the studies currently underway:
Led by nephrologist Michael S. Goligorsky, M.D., Ph.D., who heads the New York Medical College/Westchester Artificial Kidney Foundation Renal Institute (The Renal Institute), research teams are working to characterize the mechanisms of endothelial dysfunction as an early warning system of atherosclerotic, diabetic, and hypertensive vascular damage. Endothelial nitric oxide synthase represents the main parameter affected early during development of endothelial dysfunction, providing an opportunity to diagnose these conditions at a stage when symptoms are still absent.
Dr. Goligorsky studies integrins in acute renal failure, seeking the molecular pathology responsible for dislodgement of epithelial cells and the resultant tubular obstruction and renal dysfunction. Another study focuses on vascular permeability in diabetic nephropathy, and a third project explores the biology of nitric oxide (NO) in renal injury.
John Quilley, Ph.D., associate professor of pharmacology, is examining the role of oxidative stress in the form of peroxynitrite (ONOO) in contributing to diabetic kidney disease.
Dr. Goligorsky is joined by Michael Klein, M.D., Renee Garrick, M.D., and Stephen Adler, M.D., faculty members in the Department of Medicine, to study endothelial dysfunction and cardiac complications in patients with kidney disease.
Vera Delaney, M.D., Ph.D., associate professor of medicine, works with Dr. Goligorsky in studying urine proteomes to define biomarkers of kidney transplant rejection.
Julian Stewart, M.D., Ph.D., professor of pediatrics, collaborates with Dr. Goligorsky in a study of the detection of endothelial dysfunction in renal failure. These investigators also work together to develop non-invasive methods for the detection of nitric oxide in tissue, utilizing a laser Doppler system.
Research Topics in Kidney Disease
Homocysteine and asymmetric dimethylarginine, both metabolites accumulating in patients with end-stage renal disease and believed to be responsible for the increased frequency of atherosclerotic coronary artery disease, interfere with the activity of endothelial nitric oxide synthase. DNA microarray analysis revealed a panoply of genes turned on or off by these metabolites. Studies are underway that will characterize all these abnormalities on the cellular and subcellular level.
Since endothelial nitric oxide synthase (eNOS) is localized to caveolae, which can regulate its activity, recent studies have established the role of caveolar scaffolding protein, caveolin-1, in the modulation of nitric oxide synthase function. These studies are currently expanded to examine the role played by caveolin-1 and eNOS in chronic kidney disease.
These two studies have branched out into the areas of diabetic vascular complications and pathogenesis of atherosclerotic vascular lesions, especially in patients with renal failure.
Researchers have established a novel mechanism of endothelial cell senescence in diabetes—premature senescence—and have identified certain drugs that can prevent and reverse senescent phenotype. Recent data demonstrate that endothelial progenitor cells become functionally incompetent under these conditions.
In parallel with these investigations, a clinical study into the early diagnosis of endothelial dysfunction in the dialysis patients, as assessed with laser Doppler flowmetry, are in progress.
Yet another clinical study of urine samples obtained from kidney transplant recipients uses proteomics to identify diagnostic markers of kidney rejection after transplant.
NYMC-WAKF Renal Research Institute
Purpose: To engage in biomedical research and to produce scholarly programs and publications in the field of nephrology and kidney functions, ailments, conditions, and treatments.
Objectives: To facilitate translational laboratory-to-clinic research into early preclinical markers of endothelial dysfunction; to serve as a platform for educational activities including a renal fellowship training program, lecture series, and summer training for high school students; to serve as a site for annual international sabbatical professorship; and to provide summer training program for medical students.
Current research: Includes seeking mechanistic characterization of physiological functions of the kidney; establishing pathophysiologic mechanisms of cardiovascular complications in patients with, and in animal models of, renal disease; and characterizing proteomic profile of different renal diseases such as renal transplant rejection.