International Journal of Stem Cell Research and Transplantation (IJST)    IJST-2328-3548-01-001e

Renal Transplantation from Donation After Circulatory Death Donors: Evolution of Strategies

Shrestha BM

Division of Renal Transplantation, Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield, UK.

*Corresponding Author

Badri Man Shrestha MD FRCS FACS,
Division of Renal Transplantation, Sheffield Kidney Institute,
Herries Road, Sheffield, S5 7AU, UK.
Tel: +44 114 2434343
Fax: +44 114 2714604

Received: August 26, 2016; Published: September 02, 2016

Citation: Shrestha BM (2016) Renal Transplantation from Donation After Circulatory Death Donors: Evolution of Strategies. Int J Stem Cell Res Transplant. 04(2e), 1-3.

Copyright: Shrestha BM© 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

Donation after circulatory death (DCD) donors are admitted in the intensive care units, who either do not fulfil the brain-stem death criteria or in whom the withdrawal of treatment is planned because of futility of further treatment. The initial renal function and log-term outcomes of DCD renal transplantation (RT) have been a subject of concern in the transplant community because of associated deleterious effects of existing co-morbidities in the donor, elderly age and prolonged warm and cold ischaemia times [1, 2]. However, based on the enhanced understanding of the pathophysiology of DCD and experience gained over the past two decades, DCD RT has become a routine and proven a useful source of organs for transplantation. The editorial summarises the evolution of the strategies adopted to improve the outcomes of DCD RT worldwide over the past two decades.

Formerly known as non-heart beating or asystolic donors, DCD donation was introduced and succeeded in a regular basis in Maastricht by Kootstra et al., in 1989 [3]. Donors are classified as uncontrolled donors (brought in dead, unsuccessful resuscitation or cardiac arrest in hospital patient) or controlled donors (awaiting cardiac arrest or cardiac arrest after brain-stem death) [4-6]. In recent years, marked increase in DCD donation rate (per million population) has occurred in the United Kingdom (12.0), United States of America (6.3), Belgium (6.1), Spain (5.3) and Argentina (3.1) [7].

The process of organ donation for DCD has been standardised based upon the understanding of the impact of cardiorespiratory arrest on organ dysfunction and subsequent immunological events. The time allowed after withdrawal to total circulatory arrest (time-to-death; TTD) for DCD has been accepted as 2 hours, which, in one study, showed similar incidence of delayed graft function (DGF) (50.2% vs 50%), 5 year graft survival (74.1% vs 83.9%; p=0.9) and patients survival (88.8% vs. 83.9%; p=0.66) when compared with TTD of 0-1 hour [8]. The haemodynamic measurements, systolic blood pressure (SBP) and oxygen saturation of the donor during the withdrawal period has a significant influence and is predictive of DGF and graft survival. In a study including 1050 kidneys from 566 donors, the SBP was predictive of DGF (OR 1.42) and the slope of oxygen saturation during the first 10 minutes after extubation was associated with 5-year graft survival of 70.0% for donors above the median versus 61.4% for those below the median failure (below median; hazard ratio 1.30) [9].

During the retrieval surgery, use of double-balloon triple lumen catheter facilitates in situ perfusion of the organs with cold preservative solution, which has significant impact on the incidence of primary non-function (PNF) [10]. A study from UK on the effects of the type of preservation fluids such as Marshall’s (hyperosmolar citrate) and University of Wisconsin solution on the incidence of DGF, PNF, biopsy-proven acute rejection (BPAR), renal function and graft survival at one year were not significantly different. Use of Marshall’s solution was associated with significant cost-saving [11].

From the Dutch Organ Transplantation Registry, the outcomes in uncontrolled (Maastricht categories I and II) and controlled (Maastricht category III) DCD RT were examined, which showed significantly high incidence of PNF in uncontrolled DCD group (19.6% vs 96%; p≤0.001); DGF rate and estimated glomerular function rate (eGFR) after 1 and 5-year were comparable between the two groups when censored for PNF [12]. Because of high incidence of PNF, majority of transplant centres are reluctant to utilise kidneys from uncontrolled DCD donors.

The outcomes and cost-effectiveness of types of immunosuppressive agents have been evaluated in DCD RTs. In a study from the UK, induction with basiliximab and anti-thymocyte globulin (ATG) showed a significant lower rate of DGF, BPAR, infections requiring re-admission and a remarkable cost savings in the ATGinduced group [13]. The patient survival, graft survival, BPAR, eGFR did not differ between DCD RT recipients treated with alemtuzumab versus basiliximab or ATG. There was a trend towards reduced graft - and patient survival and increased incidence of cytomegalovirus and BK-virus infections in the alemtuzumabtreated group [14]. The phase III BENEFIT-EXT study assessed belatacept, versus cyclosporine in extended criteria deceased donor RTs and showed better renal function (4-7 mls/min higher mean eGFR in the belatacept group), but the BPAR, graft and patient survivals and infections were similar. The incidence of PTLD was high in the belatacept group [15].

Delayed graft function is an established complication after DCD kidney transplants, which prolongs hospital stay and impacts graft outcomes [16]. The impact of DGF on graft outcomes was examined by a paired door kidney analysis of data from Australia and New Zealand Dialysis and Transplant Registry (ANZDTR). Of the 74 pairs of DCD kidneys followed for a median of 1.9 years, 14% recipients with DGF had experienced overall graft loss compared to 4% in those without DGF (p=0.04; HR 4.31). The adjusted HR for BPAR and all-cause mortality at 3 years in recipients who have experienced DGF were 0.98 (95% CI 0.96, 1.01) and 1.70 (95% CI 0.36, 7.93), respectively, compared to recipients without DGF. Strategies aimed to reduce the risk of DGF could potentially improve graft survival in DCD kidney transplants [17].

Prolonged cold ischaemia time (CIT) is a known risk factor for DGF and has important implication for organ allocation policies. Analysis of data from ANZDTR, 24.6% experienced DGF and 33.9% experienced allograft loss over a median follow-up of 5.3 years. Recipients with total ischaemia time >/-14 hours experienced an increased risk of DGF, particularly with older DCD grafts. There was on average, a 9% increase in the overall risk of graft loss per hour increase in the total ischaemic time [p = 0.02] in recipients with older DCD grafts [18]. Logistic factors influencing the CIT was assessed prospectively in the UK by Shrestha et al., on 1763 RTs and identified DCD donors, transport time, cross-matching, recipient factors, virtual cross-match and availability of operating time as the determinants of CIT, which were modifiable [19].

The anticipation of compromised outcomes of DCD RT does lead to reduced acceptance of DCD donors by transplant centres, particularly when additional features of extended criteria donors (ECD) are present. Evaluation of data from Scientific Registry of Transplant Recipients on ECD/DCD donors showed higher kidney donor risk index among discarded versus transplanted kidneys (1.82 vs. 1.67; p=0.001). The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive [20].

A report from the UK showed 49% incidence of DGF in DCD RT, which is similar to previous reports. There was no difference in the 3-year patient (91.4 vs. 92.2%) and graft (88.2 vs. 90.0%) survival between DCD and DBD kidneys. The incidence of PNF was higher for the DCD than for DBD kidneys (4% vs. 3%; p=0.04). By far, kidneys from donors > 60 years had more than twice the risk of graft failure within 3 years of RT compared with those transplanted with kidneys from donors < 40 years (HR 2.35, p<0.0001) [21].

Since Kootstra et al., introduced machine preservation of DCD kidneys [22], the optimum method of preservation of DCD kidney using static cold storage (CS) or hypothermic machine perfusion (MP) was assessed in an international randomised controlled trial from Europe, which did not show significant difference in the incidence of DGF between the two methods of storage [23]. Follow-up of the recipients from the same study did not show significant difference in the three-year graft survival between the two methods of storage [24]. A multicentre randomised trial conducted in the UK for DCD kidneys, showed no difference in the incidence of DGF (58% vs. 56%), renal function at 3 and 12 months, graft and patient survival; thus concluding MP offered no advantage over CS and the latter was cheaper and more straightforward [25]. A systematic review suggested that hypothermic MP reduces DGF compared with static cold storage. There was no difference in PNF, BPAR, long-term renal function or patient survival [26].

There are a few isolated case reports on the efficacy of ex vivo normothermic perfusion, where kidneys, declined by several centres previously on the ground of inadequate in situ perfusion, were perfused with oxygenated packed red cells for 60 minutes ex vivo and transplanted with successful outcomes, which needs further investigation [27]. Dual kidney transplantation from adult DCD and other extended criteria donors, which otherwise might be discarded, have shown excellent medium-term outcomes and achieved reduction in waiting time particularly in older recipient population [28].

Organ shortage remains the biggest challenge in organ transplantation. To address this, special attention needs to be paid to encourage utilisation of DCD donors, modify the risk factors those influence the short-and long-term outcomes and step forward in development and optimisation of uncontrolled DCD donor programmes [29]. It is prerequisite to develop and adopt best practice guidelines for DCD in every transplant programme, which should include the decision to withdraw or limit life-sustaining in a controlled DCD setting or cessation of cardiopulmonary support in an uncontrolled DCD donation, which should be based on the patient’s best interest [30].


  1. McDonald S, Clayton P (2013) DCD ECD kidneys-can you make a silk purse from a sow's ear? Am J Transplant 13(2): 249-50.
  2. Shrestha BM (2009) Strategies for reducing the renal transplant waiting list: a review. Exp Clin Transplant 7(3): 173-9.
  3. Vromen MA, Leunissen KM, Persijn GG, Kootstra G (1988) Short- and long-term results with adult non-heart-beating donor kidneys. Transplant Proc 20(5): 743-5.
  4. Thuong M, Ruiz A, Evrard P (2016) New classification of donation after circulatory death donors definitions and terminology. Transpl Int 29(7): 749-59.
  5. Kootstra G, Daemen JH, Oomen AP (1995) Categories of non-heart-beating donors. Transplant Proc 27(5): 2893-4.
  6. van Heurn LW, Talbot D, Nicholson ML (2016) Recommendations for donation after circulatory death kidney transplantation in Europe. Transpl Int 29(7): 780-9.
  7. Matesnaz R ( 2015) International data on organ donation and transplantation 2014. Newsletter Transpant.
  8. Scalea JR, Redfield RR, Arpali E (2016) Does DCD donor time-to-death affect recipient outcomes? Implications of time-to-death at a high-volume center in the United States. Am J Transplant.
  9. Allen MB, Billig E, Reese PP (2016) Donor Hemodynamics as a Predictor of Outcomes After Kidney Transplantation From Donors After Cardiac Death. Am J Transplant 16(1): 181-93.
  10. Gok MA, Bhatti AA, Asher J (2005) The effect of inadequate in situ perfusion in the non heart-beating donor. Transpl Int 18 (10): 1142-6.
  11. O'Callaghan JM, Knight SR, Morgan RD, Morris PJ (2016) A National Registry Analysis of Kidney Allografts Preserved With Marshall's Solution in the United Kingdom. Transplantation.
  12. Peters-Sengers H, Homan van der Heide JJ, Heemskerk MB (2016) Similar 5-Year Estimated Glomerular Filtration Rate Between Kidney Transplants From Uncontrolled and Controlled Donors After Circulatory Death-A Dutch Cohort Study. Transplantation.
  13. Popat R, Syed A, Puliatti C, Cacciola R (2014) Outcome and cost analysis of induction immunosuppression with IL2Mab or ATG in DCD kidney transplants. Transplantation 97(11): 1161-5.
  14. Schadde E, D'Alessandro AM, Knechtle SJ (2008) Alemtuzumab induction and triple maintenance immunotherapy in kidney transplantation from donors after cardiac death. Transpl Int 21 (7): 625-36.
  15. Durrbach A, Pestana JM, Pearson T (2010) A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant 10 (3): 547-57.
  16. Shrestha BM, Haylor JL (2007) Factors influencing long-term outcomes following renal transplantation: a review. JNMA J Nepal Med Assoc 46(167):136-42.
  17. Lim WH, McDonald SP, Russ GR. (2016) Association between delayed graft function and graft loss in donation after cardiac death kidney transplants - a paired kidney registry analysis. Transplantation.
  18. Wong G, Teixeira-Pinto A, Chapman JR (2016) The impact of total ischaemic time, donor age and the pathway of donor death on graft outcomes after deceased donor kidney transplantation. Transplantation.
  19. Shrestha S, Bradbury L, Boal M. (2016) Logistical Factors Influencing Cold Ischemia Times in Deceased Donor Kidney Transplants. Transplantation 100(2): 422-8.
  20. Singh SK, Kim SJ (2016) Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory Death. Clin J Am Soc Nephrol 11(2): 317-23.
  21. Summers DM, Watson CJ, Pettigrew GJ (2015) Kidney donation after circulatory death (DCD): state of the art. Kidney Int 88(2): 241-9.
  22. Daemen JH, de Wit RJ, Bronkhorst MW (1996) Short-term outcome of kidney transplants from non-heart-beating donors after preservation by machine perfusion. Transpl Int 9 Suppl 1: S76-80.
  23. Moers C, Smits JM, Maathuis MH (2009) Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 360(1): 7-19.
  24. Moers C, Pirenne J, Paul A, Ploeg RJ (2012) Machine Preservation Trial Study G. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 366(8): 770-1.
  25. Watson CJ, Wells AC, Roberts RJ (2010) Cold machine perfusion versus static cold storage of kidneys donated after cardiac death: a UK multicenter randomized controlled trial. Am J Transplant 10(9): 1991-9.
  26. O'Callaghan JM, Morgan RD, Knight SR, Morris PJ (2013) Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes. Br J Surg 100(8): 991-1001.
  27. Hosgood SA, Saeb-Parsy K, Hamed MO, Nicholson ML (2016) Successful Transplantation of Human Kidneys Deemed Untransplantable but Resuscitated by Ex Vivo Normothermic Machine Perfusion. Am J Transplant.
  28. Stratta RJ, Farney AC, Orlando G (2016) Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool. Clin Transplant 30 (4): 380-92.
  29. Dominguez-Gil B, Duranteau J, Mateos A. (2016) Uncontrolled donation after circulatory death: European practices and recommendations for the development and optimization of an effective programme. Transpl Int 29(8):842-59.
  30. Haase B, Bos M, Boffa C (2016) Ethical, legal, and societal issues and recommendations for controlled and uncontrolled DCD. Transpl Int 29(7): 771-9.

         Indexed in


       Total Visitors

SciDoc Counter

Get in Touch

SciDoc Publishers
16192 Coastal Highway
Lewes, Delaware 19958
Tel :+1-(302)-703-1005
Fax :+1-(302)-351-7355

Creative Commons License
SciDoc Publishers is licensed under a Creative Commons Attribution 4.0 International License.