Intensive Insulin Therapy in Deceased Donors

Every year in the US, there is a shortage of many thousands of kidneys needed for
transplant. Furthermore, kidneys that are available and are transplanted often exhibit
delayed or slow graft function (DGF and SGF, respectively), which lowers quality of life for
patients and their families and requires significant additional medical care. These needs
result in significant but preventable human suffering and health care spending. To address
these needs, the investigators' project will test the use of intensive insulin therapy (IIT)
in donors after neurological determination of death (DNDDs) as an intervention that will
decrease acute kidney injury and improve renal function at the time of organ recovery. This
should translate into a decreased incidence of DGF and SFG in recipients receiving organs
from the IIT group. The investigators also expect to find a trend toward an increase in the
number of organs available for transplant due to better organ protection in the DNDD. Taken
together, these data can provide the requisite justification for a larger study that can be
powered to evaluate the effect of IIT on increasing the number of kidneys available for
transplantation.

There is evidence that brain death often leads to hyperglycemia that may negatively impacts
the organs of DNDDs. These observations led us to conduct a retrospective study, in which
the investigators found that hyperglycemia in DNDDs is indeed associated with decreased
terminal renal function. Because it has been reported that intensive insulin therapy (ITT)
is renoprotective in the ICU more than conventional insulin therapy (CIT), the investigators
propose to evaluate the use of IIT on DNDDs to: (1) improve organ function, (2) reduce DGF
in recipients, and (3) possibly increase the number of kidney available for transplant.

Methods: This is a prospective observational study to document the impact of IIT on acute
kidney injury in DNDDS and on allograft function in recipients. DNDDs will be divided into
two groups: CIT and IIT. In the first study, the investigators will evaluate the effect of
ITT on biochemical parameters in blood samples that predict kidney health and function in
DNDDs. All methods used in this proposal are well documented in the literature and
established in the applicant's laboratory. In the investigators' second study, they will
compare the effects of ITT in DNDDs on graft function in allograft recipients in terms of
number of patients showing either DGF or SGF. Additionally, there is currently no
established set of advanced biochemical criteria in DNDDs for predicting kidney function in
recipients. The investigators will correlate the evaluated biochemical markers of kidney
function and health in order to possibly develop more refined methods of predicting
transplant success. Such a set of criteria would be useful for designing studies to
systematically test additional interventions in DNDDs to further improve organ function
before recovery and further increase the number of available organs.

Taken together, the results of this study may lead to new therapies that significantly
improve patient outcomes while significantly reducing disease associated costs. These
results can also set the stage for a follow on study for increasing the number of kidneys
available for transplant.