Renal Protection in the Organ Donor

Medical Suitability

Because of the shortage of donated organs and advances in transplantation medicine, the criteria for donor suitability are constantly broadening. As with other therapies, a decision about whether to accept an organ for transplantation must be individualized based on risk and benefit analysis in the particular recipient.

Absolute contraindications to kidney donation are few but include metastatic or incurable malignant disease (or a history of malignancy that poses a high risk for subsequent transmission) and transmissible spongiform encephalopathy such as Creutzfeldt-Jacob disease (CJD). Although HIV generally is considered an absolute contraindication, there has been some recent experience with kidney donation from HIV-infected deceased donors to HIV-infected recipients with favorable outcomes. Patients with a history of malignancy and a long cancer-free interval represent a small risk of transmission and should be considered as potential donors. Treated bacterial infection, including bacterial meningitis, also should not be considered a contraindication. Organs from potential donors infected with (or with evidence of past infection with) hepatitis B virus (HBV) may be transplanted into recipients infected with the same virus, or indeed HBV-immune recipients with careful consideration of posttransplantation passive immunoprophylaxis and antiviral therapy. Although hepatitis C–infected donors have been considered for donation only generally to hepatitis C–infected kidney recipients, the recent availability of direct-acting antivirals may alter this. Patients with negative testing for HIV and hepatitis C but with a history of intravenous drug use or other risk factors for contracting these blood-borne viruses should be referred to the donor agency for careful exploration of the risk to potential recipients.

Medical comorbidities in the donor that potentially affect recipient graft function, including hypertension, acute kidney injury, and vascular disease, as well as age, previously were incorporated into an expanded criteria donor (ECD) stratification in the United States for offer to preconsented potential recipients. More recently, a new kidney allocation system has been developed, using 10 donor factors (those listed above in addition to diabetes mellitus, proposed DCD pathway, and others) to calculate a Kidney Donor Risk Index (KDRI), which is a prediction of graft function on a continuous scale. As well as providing improved survival matching of donor graft and recipient, an outcome of this system and others such as the Eurotransplant Senior Program initiative is to maximize access to transplantation through use of organs that otherwise may not be able to be matched to a recipient. Whatever local system is in place, neither donor age nor any of these comorbidities universally precludes kidney donation, and a survival benefit for ECD kidney transplantation has been demonstrated when compared with “standard therapy” of waiting for a non-ECD kidney.

Brain Death and Physiologic Sequelae

Brain death is associated with progressive physiologic instability that ultimately can affect kidney graft function after transplantation ( Fig. 132.1 ). Timely confirmation of brain death, referral to the organ donor agency, and procurement of organs minimize the loss of donors and maximize the number of organs suitable for transplantation. Reported loss of potential donors through failed physiologic support ranges from 5% to 25%. Those who medically manage the potential donor and oversee the logistics of organ donation should work to minimize this loss through ensuring timely procurement and provision of excellent supportive treatment.

Brain death may develop as a result of progressive brain swelling in the hours or days after a severe brain injury (e.g., trauma, cerebral hemorrhage, cerebral infarction, anoxic injury). Because the brain is contained within a rigid skull that limits its expansion, progressive edema and/or hemorrhage results in rising intracranial pressure and inadequate cerebral perfusion pressure. A cycle of cerebral infarction, edema, and further increase in intracranial pressure occurs with eventual loss of blood flow to the entire brain, including the brainstem. Brain death has implications on maintaining homeostasis with potential effects on kidney graft function as described below. Moreover, acute neurologic injury and acute kidney injury may coexist not only because of shared risk factors but also through kidney-brain crosstalk (e.g., mediated by cytokine secretion, inflammation, or oxidative damage ).

Management of the Brain-Dead Potential Organ Donor

Intensivist-led management of brain-dead organ donors has been shown to be associated with retrieval of more organs for transplantation. The approach to management for the potential organ donor after brain death is similar to that for other critically ill patients with the aim of achieving and maintaining physiologic homeostasis. Meeting predefined donor management goals is associated with a reduction in delayed graft function, and consensus guidelines recommend consideration of the usual spectrum of invasive and noninvasive monitoring strategies. As a minimum this will require arterial pressure (and generally central venous pressure) monitoring, although there is no evidence to guide selection of an optimum monitoring tool. Earlier protocols and guidelines advocated the use of a pulmonary artery catheter (PAC). A more recent retrospective study of PAC use in donors at a single center showed a decline in use over time and no association with increased retrieval of kidneys for transplantation, albeit an association with increased heart procurement. A protocolized fluid and vasopressor management algorithm using minimally invasive hemodynamic monitoring (pulse-pressure-variation) has been evaluated in a multicenter randomized trial with no increase in the number of organs transplanted per donor.

An awareness of the specific perturbations that may occur in brain death and timely institution of appropriate supportive treatment is essential.