The primary research focus of Dr. Misra's lab is to identify the biological mechanisms of hemodialysis access graft failure so that novel therapies can be developed to improve outcomes for patients with end-stage renal disease. Our lab also studies acute kidney injury caused by radiocontrast agents.
It's estimated that there are about 600,000 people with end-stage renal disease (ESRD) in the United States. Because of the shortage of kidneys available for renal transplantation, the vast majority of patients with ESRD require hemodialysis as the major mode of renal replacement therapy.
The hemodialysis access graft, known as an arteriovenous fistula (AVF), is the lifeline of patients on dialysis because its optimal function is needed to purify the blood and maintain electrolyte balance. These grafts are not durable, however, and only about 62% of the grafts are functioning at one year and only 25% are functioning at two years. Health care costs related to hemodialysis access dysfunction are estimated at $1 billion annually, posing an enormous medical and financial burden for many patients.
Our current research projects on arteriovenous fistula grafts and kidney injury include:
IEX-1 protein. Our lab has previously shown that expression of the IEX-1 protein is increased in venous stenoses isolated from failed arteriovenous fistula grafts. To test if decreasing IEX-1 expression decreases venous stenosis formation, we used a porcine AVF model treated with calcitriol, a drug shown to decrease IEX-1 protein expression, at the moment of graft creation.
Oxygen nanoscaffold. Because of altered blood flow and sheer stress at the graft, it's common for AVFs to develop hypoxia. Hypoxic conditions can lead to a monocyte-macrophage response and graft failure. To test if we can prevent hypoxia within the graft, we created an oxygen-loaded scaffold to support the graft. This scaffold slowly elutes oxygen. We applied the scaffold to a murine AVF model to test if the scaffold prevents hypoxia at the graft.
Gender differences in AVF patency and treatment. It has been assumed that AVF failure rates and efficacy of treatments shouldn't differ by gender. However, preliminary data from our lab suggest that there are significant gender differences in the biological mechanisms of graft failure. We're now investigating protein expression levels in murine AVF models to examine differences in protein expression rates by gender.
Terazosin. Our lab is also investigating acute kidney injury caused by radiocontrast agents in patients with preexisting renal injury or diabetes, or both. Terazosin, when administered with radiocontrast agents, is thought to protect against contrast-induced nephropathy. Our research team is studying the potential protective effects of terazosin in a chronic kidney disease murine model.