Lab Overview

Alkesh Jani, MD is the Renal Section Chief at the Rocky Mountain Regional VAMC and a Professor of Medicine in the Division of Nephrology and Hypertension at the University of Colorado. Our current areas of research include studying the underlying causes of delayed graft function of solid organ transplants, cold ischemic injury, renal function during hibernation, cell death pathways in VCA transplants and vaccine responses in patient with chronic kidney disease and ESRD.

Kidney transplantation is the gold standard treatment of ESRD. Delayed graft function refers to failure of a kidney transplant to work in the first 1-2 weeks post-transplant and is most commonly due to tubular epithelial cell apoptosis and ATN. Deceased donor kidneys are subjected to a period of cold storage, referred to as Cold Ischemia (CI), prior to transplant. Several studies have identified prolonged CI time (CIT) as a risk factor for the development of DGF. We have recently identified novel pathways of cellular death in donor kidneys subjected to cold ischemia followed by kidney transplantation. Using a cocktail of cell death inhibitors we have demonstrated improved graft function and histology Inhibition. Our overall goal is to develop a new preservation solution for solid organ and composite vascular transplants that incorporates inhibitors of cell death and permits enhanced organ preservation.

We are also studying the ability of hibernating mammals to tolerate prolonged cold ischemia and significant reductions in heart and respiratory rate. We believe understanding of the mechanisms by which hibernating mammals are protected may have important implications for transplant medicine and organ preservation.

Another area of research for our lab is understanding impaired responses to vaccines in patients with CKD and ESRD. The incidence of pneumonia amongst dialysis patients is increasing and leads to a mortality rate that is 14-16 fold greater than pneumonia in the general population. Our preliminary data suggests that antibody production and duration in response to older version polysaccharide pneumococcal vaccines is reduced in CKD and ESRD, but the response to newer generation protein conjugate vaccines is unknown. Furthermore, the cause of decreased antibody production and duration in response to pneumococcal vaccines is unknown. We are studying whether CKD and ESRD affect the ability of the newer generation protein conjugate vaccines to elicit functional capsule-specific antibodies in the systemic (blood) and respiratory mucosa (nasal) and the effects on TFH and cellular and molecular B cell biology that underlie the rigor and quality of responses in each compartment.