Improving Outcomes in DCD Renal Transplantation

1. Improving Outcomes in DCD Renal Transplantation Reference: Hoogland ERP, Snoeijs MGJ, van Heurn LWE. DCD kidney transplantation: Results and measures to improve outcome. Curr Opin Organ Transplant. 2010;15:177–182.

2. In end-stage renal disease (ESRD), renal transplantation is the treatment of choice; however, shortage of organ donors creates a major set back. • The liberal use of kidneys from donors after cardiac death (DCD) holds the potential to increase the number of organ donors by 2.5–4 times, which is sufficient to reduce or even eliminate the waiting lists for kidney transplantation. • Unlike the donation after brain death (DBD), organs from DCD donors inevitably sustain a period of warm ischemia from circulatory arrest until initiation of organ preservation, which causes ischemic acute kidney injury, which results in an increased incidence of delayed graft function (DGF) and primary nonfunction (PNF) as compared with kidney transplantation from conventional brain-dead donors. • These early complications associated with DCD kidney transplantation are the reason for the disinclination of using these kidneys for transplantation.

3. At the first international workshop on DCD donation in Maastricht, 1995, four categories were discussed and accepted to categorize DCD kidneys according to their period of warm ischemia (see Table 1). • The longest warm ischemia time occurs in category I donors, whereas categories III and IV have potentially the shortest time. • Categories I and II represent ‘uncontrolled’ donors, as these donors are dead on arrival or undergo unsuccessful resuscitation, respectively. ‘Controlled’ donors of the categories III and IV are from the intensive care unit when withdrawal of medical treatment is planned or cardiac arrest in brain-dead patients occurs.

4. Outcomes of Kidney Transplantationfrom DCD • Results from comparative studies involving DCD and DBD kidney transplantation have shown a relatively high incidence of PNF in DCD kidneys, which has been attributed to the ischemic injury suffered before organ recovery. • The incidence of PNF could be as high as 15–25%, based on the threshold to discard or to accept DCD kidneys for transplantation. • A method to improve the results of DCD kidney transplantation without changing the selection criteria is by better recipient management. • Careful fluid management of the recipient with intraoperative systolic blood pressure above 110 mmHg and central venous pressure above 6 cm H2O reduces the probability of PNF 3–10 times. • Recently (2009), the Leicester group reported that the results of functioning DCD kidneys were similar to DBD kidneys after a follow-up period ranging from 5 to 15 years for mainly uncontrolled (Maastricht category II) kidneys, despite higher rates of DGF. • This is in confirmation of the results that reveal the long-term outcome (follow-up up to 25 years) of viable DCD kidneys that was equivalent to grafts recovered from brain-dead donors.

5. Standard Preservation Techniques forDCD Renal Transplantation • In several centers, in situ preservation (ISP) is the method of choice for uncontrolled, Maastricht categories I and II, DCD donors. • It is an indispensable technique that can provide the opportunity to meet legal and logistical requirements for organ recovery without excessive warm ischemia times, besides the transplantation procedures can be initiated prior to consent for organ donation depending on the legal opportunities. • In Maastricht category III donors, withdrawal of life support usually takes place in the ICU. • The patient after cardiac arrest and the obligatory no-touch period, is transported to the operating room, after which rapid laparotomy is performed with direct cannulation of the aorta. • The warm ischemia time with this technique can be limited to 20 min. • In order to keep the transportation time to a minimum, a short distance between the ICU and the operating room has to be maintained.

6. New Developments in Donor Management Before and During Organ Preservation • Cardiopulmonary resuscitation (CPR) can be used while preservation measures are taken in category II donors to reduce ischemic damage to the kidney of a potential donor, while maintaining an adequate circulation after cardiac arrest and a no-touch period of 5 min. • Data indicate that despite CPR, donor kidneys suffer extensive warm ischemic injury. • In order to improve CPR by performing consistent rates and depths of chest compressions, a variety of automated chest compression devices have been studied. • Their reports describe improved hemodynamic effects and better coronary perfusion with increased peak aortic pressure over manual CPR.

7. New Developments in Donor Management Before and During Organ Preservation • Chest compression devices, such as the AutoPulse (ZOLL Circulation, Sunnyvale, California) (see Fig. 2), are used to preserve DCD donor organs from cardiac arrest until in situ cooling using a double-balloon triple-lumen (DBTL) catheter. • Moreover, extracorporeal membrane oxygenation (ECMO) has the potential to improve organ quality by providing normal tissue perfusion after cardiac death. • Since its introduction in the early 1970, it has become a standard therapy to provide temporary circulatory support and systemic oxygenation for patients with reversible cardiac or respiratory failure that cannot be supported with conventional mechanical ventilation.

8. Fig. 2: Chest compression device: AutoPulse

9. Results of in-situ Preservation andDirect Cannulation of the Aorta • In controlled DCD donors, rapid laparotomy and direct cannulation of the aorta has lead to a significantly superior graft survival compared to DCD donor kidneys that are preserved in situ. • These donors have shorter warm ischemia times and lower rates of discard. • Therefore, rapid laparotomy and direct aortic cannulation is considered preferable above in situ perfusion using DBTL catheters as the method for initiation of organ preservation in controlled DCD donors.

10. Preservation and Assessment of Kidneys after Recovery • After successful organ recovery from DCD, kidneys are stored either on melting ice or on a pulsatile cold perfusion machine, which may provide a useful platform to assess the kidney function by several viability tests; Subsequent to the assessment of acute ischemic injury, kidneys from old donors can have chronic degenerative changes. • The only proven predictor for graft function and survival among several selection criteria is histological assessment of degenerative changes in pretransplant kidney biopsies in donors aged ≥60 years. • Preimplantation histological kidney damage is associated with premature graft loss in older donors compared to donor age, kidney function, kidney weight and perfusion parameters. • As a result, histological assessment of renal biopsies is a clinically useful tool to select kidneys from donors with satisfactory outcome, which is a better approach than setting arbitrary age limits for kidney donation.

11. Conclusion • The risk of DGF and PNF with DCD kidneys can be reduced primarily by organ preservation using rapid laparotomy and direct aortic cannulation for controlled DCD donors and thereafter by reducing the warm ischemia time using automated chest compression devices and ECMO. In order to improve the treatment of waitlisted dialysis patients, expansion of the donor pool by using more uncontrolled donors supported with ECMO is of paramount importance. • Improving the quality of DCD kidneys with continued and novel methods can expand the utilization of this large pool of donor kidneys to its full potential.