The Effect of Therapeutic Hypothermia on Deceased Donor Renal Graft Outcomes - a Randomized Controlled Trial From the Region 5 Donor Management Goals Workgroup

The number of kidneys available for transplantation in the U.S. (~15,000/yr) does not meet
demand (~80,000/yr). This discrepancy will likely worsen given the increasing U.S.
prevalence of chronic kidney disease and is compounded by sizable organ attrition once
organs have entered the donation process (25-30% attrition in Region 5). Furthermore,
worsening renal function in donation after neurologic determination of death (DNDD) organ
donors (an increasingly important source of allografts) is one of the strongest predictors
of delayed graft function (DGF) and slow graft function (SGF) in the recipient. Both DGF
and SGF are associated with decreased long-term organ survival and are of major concern to
the transplant community.

To alleviate the aforementioned supply-demand imbalance, there are two major unmet needs
that must be urgently addressed. First, active medical interventions that are tested
prospectively to protect the organ during the donation process hold sizable potential, but
remain exceedingly rare. Second, compliance with pre-defined donor management protocols to
restore and stabilize deceased organ donor physiologic functions remains low across
different donation service areas, despite evidence that these protocols may improve organ
yield.

The goal of this proposal, therefore, is to demonstrate that (1) therapeutic hypothermia as
an active medical intervention for the DNDD donor and (2) compliance with donor management
protocols can substantially improve allograft function and survival.

The investigators will accomplish this goal by extending an existing research infrastructure
(HRSA, R380T10586) across several donor service areas. As such, the investigators will
bring together a research network and use the power of this network to properly test a
simple medical intervention, therapeutic hypothermia for renal protection, in a prospective
randomized single blinded trial. Therapeutic hypothermia is an established cytoprotective
intervention that has been demonstrated to be highly protective of organs in select
critically ill patients. By combining two of the largest donation service areas in the
nation (CTDN, Northern California and OneLegacy, Southern California), the investigators
will have access to approximately 10% of all organ donors in the nation. This proposal aims
to randomize 500 DNDD organ donors, the biggest cohort enrolled in a prospective randomized
trial.

The investigators will further leverage this network to track trial specific donor
management protocols variables goals and drive tighter compliance with already established
donor management protocols across all donor service areas in Region 5. This will allow the
investigators to compile a large historical control cohort that will facilitate answering
additional research questions with great detail. All organ procurement areas in Region 5
have confirmed their willingness to participate in this effort and contribute relevant organ
donor data via a shared web-portal. Through this active participation, a secondary gain
will be improved reporting of donor data and compliance with already accepted donor
management goals.

Test of feasibility will be improvement in various kidney function metrics that are commonly
used to evaluate organ health during the donation process. Ultimately, the investigators
believe this multi-pronged approach may lead to 800 to 1000 additional kidneys that are
successfully transplanted nationwide each year.

Inclusion Criteria:

- > 18 years of age, deceased organ donor

Exclusion Criteria:

- < 18 years of age, not a deceased organ donor