Hypothermic Machine Perfusion as a National Standard Preservation Method for Deceased Donor Kidneys.

BACKGROUND: Recently, continuous nonoxygenated hypothermic machine perfusion (HMP) has been implemented as standard preservation method for deceased donor kidneys in the Netherlands. This study was designed to assess the effect of the implementation of HMP on early outcomes after transplantation. METHODS: Kidneys donated in the Netherlands in 2016 and 2017 were intended to be preserved by HMP. A historical cohort (2010-2014) preserved by static cold storage was chosen as the control group. Primary outcome was delayed graft function (DGF). Additional analyses were performed on safety, graft function, and survival up until 2 y after transplantation. RESULTS: Data were collected on 2493 kidneys. Analyses showed significantly more donation after circulatory death, preemptive transplantation, and retransplants in the project cohort. Of the 681 kidneys that were transplanted during the project, 81% were preserved by HMP. No kidneys were discarded due to HMP-related complications. DGF occurred in 38.2% of the project cohort versus 43.7% of the historical cohort (P < 0.001), with a significantly shorter duration within the project cohort (7 versus 9 d, P = 0.003). Multivariate regression analysis showed an odds ratio of 0.69 (95% confidence interval, 0.553-0.855) for the risk of DGF when using HMP compared with cold storage (P = 0.001). There was no significant difference in kidney function, graft survival, and recipient survival up until 2 y posttransplantation. CONCLUSIONS: This study showed that HMP as a standard preservation method for deceased donor kidneys is safe and feasible. HMP was associated with a significant reduction of DGF.

Appointing nurses trained in organ donation to improve family consent rates.

BACKGROUND: One of the most important bottlenecks in the organ donation process worldwide is the high family refusal rate. AIMS AND OBJECTIVES: The main aim of this study was to examine whether family guidance by trained donation practitioners increased the family consent rate for organ donation. DESIGN: This was a prospective intervention study. METHODS: Intensive and coronary care unit nurses were trained in communication about donation (ie, trained donation practitioners) in two hospitals. The trained donation practitioners were appointed to guide the families of patients with a poor medical prognosis. When the patient became a potential donor, the trained donation practitioner was there to guide the family in making a well-considered decision about donation. We compared the family consent rate for donation with and without the guidance of a trained donation practitioner. RESULTS: The consent rate for donation with guidance by a trained donation practitioner was 58.8% (20/34), while the consent rate without guidance by a trained donation practitioner was 41.4% (41/99, P = 0.110) in those patients where the family had to decide on organ donation. CONCLUSIONS: Our data suggest that family guidance by a trained donation practitioner could benefit consent rates for organ donation. RELEVANCE TO CLINICAL PRACTICE: Trained nurses play an important role in supporting the families of patients who became potential donors to guide them through the decision-making process after organ donation request.

Physician Experiences with Communicating Organ Donation with the Relatives: A Dutch Nationwide Evaluation on Factors that Influence Consent Rates.

BACKGROUND: The aim of this nationwide observational study is to identify modifiable factors in communication about organ donation that influence family consent rates. METHODS: Thirty-two intensivists specialized in organ donation systematically evaluated all consecutive organ donation requests with physicians in the Netherlands between January 2013 and June 2016, using a standardized questionnaire. RESULTS: Out of 2528 consecutive donation requests, 2095 (83%) were evaluated with physicians. The questionnaires of patients registered with consent or objection in the national donor registry were excluded from analysis. Only those questionnaires, in which the family had to make a decision about donation, were analyzed (n = 1322). Independent predictors of consent included: requesting organ donation during the conversation about futility of treatment (OR 1.8; p = 0.004), understanding of the term 'brain death' by the family (OR 2.4; p = 0.002), and consulting a donation expert prior to the donation request (OR 3.4; p < 0.001). CONCLUSIONS: Our study showed that decoupling the organ donation conversation from the conversation about futility of treatment was associated with lower family consent rates. Comprehension of the concept of brain death by the family and consultation with a transplant coordinator before the organ donation request by the physician could positively influence consent rates.

Evolution of Deceased Organ Donation Activity Versus Efficiency Over a 15-year Period: An International Comparison.

BACKGROUND: The donation rate (DR) per million population is not ideal for an efficiency comparison of national deceased organ donation programs. The DR does not account for variabilities in the potential for deceased donation which mainly depends on fatalities from causes leading to brain death. In this study, the donation activity was put into relation to the mortality from selected causes. Based on that metric, this study assesses the efficiency of different donation programs. METHODS: This is a retrospective analysis of 2001 to 2015 deceased organ donation and mortality registry data. Included are 27 Council of Europe countries, as well as the United States. A donor conversion index (DCI) was calculated for assessing donation program efficiency over time and in international comparisons. RESULTS: According to the DCI and of the countries included in the study, Spain, France, and the United States had the most efficient donation programs in 2015. Even though mortality from the selected causes decreased in most countries during the study period, differences in international comparisons persist. This indicates that the potential for deceased organ donation and its conversion into actual donation is far from being similar internationally. CONCLUSIONS: Compared with the DR, the DCI takes into account the potential for deceased organ donation, and therefore is a more accurate metric of performance. National donation programs could optimize performance by identifying the areas where most potential is lost, and by implementing measures to tackle these issues.

Imprecise definitions of starting points in retrospectively reviewing potential organ donors causes confusion: call for a reproducible method like 'imminent brain death'.

Low donor supply and the high demand for transplantable organs is an international problem. The efficiency of organ procurement is often expressed by donor conversion rates (DCRs). These rates differ among countries, but a uniform starting point for defining a potential heart-beating donor is lacking. Imprecise definitions cause confusion; therefore, we call for a reproducible method like imminent brain death (IBD), which contains criteria in detail to determine potential heart-beating donors. Medical charts of 4814 patients who died on an ICU in Dutch university hospitals between January 2007 and December 2009 were reviewed for potential heart-beating donors. We compared two starting points: 'Severe Brain Damage' (SBD) (old definition) and IBD (new definition), which differ in the number of absent brainstem reflexes. Of the potential donors defined by IBD 45.6% fulfilled the formal brain death criteria, compared with 33.6% in the larger SBD group. This results in a higher DCR in the IBD group (40% vs. 29.5%). We illustrated important differences in DCRs when using two different definitions, even within one country. To allow comparison among countries and hospitals, one universal definition of a potential heart-beating donor should be used. Therefore, we propose the use of IBD.

Appointing 'trained donation practitioners' results in a higher family consent rate in the Netherlands: a multicenter study.

The consent process for organ and tissue donation is complex, both for families and professionals. To help professionals in broaching this subject we performed a multicenter study. We compared family consent to donation in three hospitals between December 2007 and December 2009. In the intervention hospital, trained donation practitioners (TDP) guided 66 families throughout the time in the ICU until a decision regarding donation had been reached. In the first control hospital, without any family guidance or training, 107 families were approached. In the second control hospital 'hostesses', who were not trained in donation questions, supported 99 families during admittance. A total of 272 families were requested to donate. We primarily compared consent rates, but also asked families about their experiences through a questionnaire. Family consent rate was significantly higher in the intervention hospital: 57.6% (38/66), than in the control hospitals: 34.6% (37/107) and 39.4% (39/99). The 69% response rate to the questionnaire -~5 months after death - showed no confounding variables that could have influenced the consent rate. Appointing TDPs in the intervention hospital to guide families during admittance and the donation decision-making process, results in higher family consent rates.

Eight years of outcomes of the Dutch Living Donor Kidney Exchange Program.

In January 2004, the Dutch transplant centers agreed on a protocol for a national Living Donor Kidney Exchange Program for ABO blood type incompatible and positive cross match donor-recipient pairs. Here, we report the results of that program. All transplants performed within the Living Donor Kidney Exchange Program between January 2004 and December 2011 were analysed. We collected demographic data of recipients and donors. Univariate and multivariate Cox proportional hazard analyses were performed, including recipient age, donor age, and reason for participation in the exchange program. We studied overall uncensored survival and graft survival censored for death in both ABO blood type incompatible and positive cross match groups. We enrolled 472 donor-recipient combinations, consisting of 269 ABO blood type incompatible pairs and 203 positive cross match pairs. In the end, we performed 187 kidney transplants (40% of those enrolled) with 83 ABO blood type incompatible and 104 positive cross match pairs. Most of the transplanted recipients (119/187, 64%) had an age difference of less than 5 years with their original incompatible donors. The age differences with their actual donors varied widely, but the number of recipients with a donor > 5 years older was comparable to the number of recipients with a donor > 5 years younger. In the multivariate Cox analysis, age as a continuous variable was found to have a significant influence on graft failure. Nevertheless, the 5-year uncensored survival (85%) and the graft survival censored for death (89%) were excellent and comparable to the results of direct living donation. No differences were found between the ABO incompatible and the positive cross match groups. The Dutch Living Donor Kidney Exchange Program has a high transplant rate of 40%, with excellent 5 year graft survival.

Higher refusal rates for organ donation among older potential donors in the Netherlands: impact of the donor register and relatives.

BACKGROUND: The availability of donor organs is considerably reduced by relatives refusing donation after death. There is no previous large-scale evaluation of the influence of the Donor Register (DR) consultation and the potential donor's age on this refusal in The Netherlands. METHODS: This study examines 2101 potential organ donors identified in intensive care units between 2005 and 2008 and analyzes the association of DR consultation and subsequent refusal by relatives and the relationship with the potential donor's age. RESULTS: Of the 1864 potential donor cases where the DR was consulted, the DR revealed no registration in 56%, 20% registration of consent, and 18% objection. In the other 6.5% of cases, where the DR indicated that relatives had to decide, the relatives' refusal rate was significantly lower than in the absence of a DR registration (46% vs. 63%). In 6% of the cases where the DR recorded donation consent, relatives still refused donation. DR registration, objection in the DR, and the relatives' refusal rate if the DR was not decisive increased with donor age. CONCLUSIONS: Despite the introduction of a DR, relatives still play an equally important role in the final decision for organ donation. The general public should be encouraged to register their donation preferences in the DR and also to discuss their preferences with their families. The higher refusal rate of older potential donors means that this group should receive more information about organ donation, especially because the cohort of available donors is ageing.

The optimal chain length for kidney paired exchanges: an analysis of the Dutch program.

Living donor kidney exchange programs offer incompatible donor-recipient pairs the opportunity to be transplanted. To increase the number of these transplants, we examined in our actual donor-recipient couples how to reach the maximum number of matches by using different chain lengths. We performed 20 match procedures in which we constructed four different chain lengths: two, up to three, up to four and unlimited. The actual inflow and outflow of donor-recipient couples for each run were taken into consideration in this analysis. The total number of matched pairs increased from 148 pairs for only two-way exchanges to 168 for three-way exchanges. When a chain length of 4 was allowed five extra couples could be matched over a period of 5 years. Unlimited chain length did not significantly affect the results. The optimal chain length for living donor kidney exchange programs is 3. Longer chains with their inherent logistic burden do not lead to significantly more transplants.

Organ donation performance in the Netherlands 2005-08; medical record review in 64 hospitals.

BACKGROUND: The Netherlands has a low number of deceased organ donors per million population. As long as there is a shortage of suitable organs, the need to evaluate the donor potential is crucial. Only in this way can bottlenecks in the organ donation process be detected and measures subsequently taken to further improve donation procedures. METHODS: Within a time frame of 4 years, 2005-08, medical charts of all intensive care deaths in 64 hospitals were reviewed by transplant coordinators and donation officers. Data were entered in a web-based application of the Dutch Transplant Foundation, both to identify the number of potential organ donors (including donation after cardiac death), as well as to analyse the reasons for potential donor loss. RESULTS: In total, 23 508 patients died in intensive care units, of which 64% were younger than 76 years. The percentage of all potential organ donors out of the total number of deaths decreased from 8.2% in 2005 to 7.1% in 2008. Donor detection increased from 96% in 2005 to 99% in 2008. Of the potential donors, 17-21% recorded consent and 17-18% recorded objection in the national Donor Register. If the Donor Register was not decisive, the consent rate of families approached for organ donation was 35% in 2005, 29% in 2006, 41% in 2007 and 31% in 2008. The overall conversion rate (the number of actual donors divided by the number of potential donors) was 30%, 26%, 35% and 29% in these years. In the group of potential donor losses, objection by families accounted for about 60% during this study. CONCLUSIONS: This study showed that the maximal number of potential organ donors is about three times higher than the number of effective organ donors. The main reason accounting for approximately 60% of the potential donor losses was the high family refusal rate. The year 2007 showed that a higher percentage of deceased organ donors can be procured from the pool of potential donors. All improvements should focus on decreasing the unacceptably high family refusal rates.

A plea for uniform European definitions for organ donor potential and family refusal rates.

Conversion of potential organ donors to actual donors is negatively influenced by family refusals. Refusal rates differ strongly among countries. Is it possible to compare refusal rates in order to be able to learn from countries with the best practices? We searched in the literature for reviews of donor potential and refusal rates for organ donation in intensive care units. We found 14 articles pertinent to this study. There is an enormous diversity among the performed studies. The definitions of potential organ donors and family refusal differed substantially. We tried to re-calculate the refusal rates. This method failed because of the influence caused by the registered will on donation in the Donor Register. We therefore calculated the total refusal rate. This strategy was also less satisfactory considering possible influence of the legal consent system on the approach of family. Because of lack of uniform definitions, we can conclude that the refusal rates for organ donation can not be used for a sound comparison among countries. To be able to learn from well-performing countries, it is necessary to establish uniform definitions regarding organ donation and registration of all intensive care deaths.

Hurdles, barriers, and successes of a national living donor kidney exchange program.

BACKGROUND: Living donor kidney exchange is now performed in several countries. However, no information is available on the practical problems inherent to these programs. Here, we describe our experiences with 276 couples enrolled in the Dutch program. METHODS: Our protocol consists of five steps: registration, computerized matching, crossmatching, donor acceptation, and transplantation. We prospectively collected data of each step of the procedure. RESULTS: Of the 276 registered pairs we created 183 computer-matched combinations. However, 62 of 183 recipients proved to have a positive crossmatch with their new donor, which was not predicted by the screening results of the recipient centers. Alternative solutions were found for 39 couples, resulting in a total of 160 new combinations with negative crossmatches. Thereafter, because of 22 individual clinical problems, the exchange procedure had to be discontinued for 51 couples while only for 19 of them alternative solutions were found. At the end of day, 128 patients had received exchange kidneys, 55 were transplanted outside the program, 59 are still on the crossover waitlist, and 34 had left the program for medical or psychological reasons. CONCLUSION: A living donor kidney exchange program is a dynamic process. Many clinical hurdles and barriers are encountered that for a large part were not foreseen but should be taken into account when programs are initiated based on computer simulations. Success is dependent on a flexible organization able to create alternative solutions when problems arise. Centralized allocation and crossmatch procedures are instrumental in this respect.

A flexible national living donor kidney exchange program taking advantage of a central histocompatibility laboratory: the Dutch model.

The shortage of deceased donor kidneys for transplantation has resulted in the expansion of living donation programs. A number of possibilities have been explored, since it became clear that donors do not need to be genetically related to their recipients. Apart from classical direct donation, other options such as paired exchange, list exchange, altruistic donation and domino paired exchange programs have been implemented. In the Netherlands, patients who cannot be transplanted with their potential living donor because of ABO blood group incompatibility or a positive crossmatch, have the option to participate in a national paired kidney exchange program. The practical issues related to this program are described. The 5-years experience with the Dutch kidney exchange program is very positive as, so far, 42% of the recipients included have been transplanted. Recommendations are given for a successful implementation of a common kidney exchange program of different transplantation centers focusing on the advantage of a central histocompatibility laboratory.

A highly efficient living donor kidney exchange program for both blood type and crossmatch incompatible donor-recipient combinations.

BACKGROUND: Lack of deceased donors for kidney transplant patients in the Netherlands encouraged alternative options to expand the living donor pool for recipients who have a willing donor but cannot donate directly because of a positive crossmatch or ABO blood type incompatibility. A national donor kidney exchange was considered as a possible solution. METHODS: From January 2004 until June 2006, 146 couples from seven kidney transplantation centers were enrolled and participated in 10 match procedures. The Dutch Transplant Foundation was responsible for the allocation and the National Reference Laboratory for Histocompatibility in Leiden performed all the serological crossmatches. RESULTS: For 72 out of the 146 (49%) donor-recipient combinations, a match was found. The success rate in the positive crossmatch group was significantly (P = 0.0015) higher than in the ABO-incompatible group (44/69 vs. 28/77); median panel reactive antibodies of the matched recipients in the positive crossmatch group was 38% (0-100) and in the ABO-incompatible group 0% (0-27; P < 0.001). We were least successful for ABO blood type incompatible pairs with blood type O recipients, but for 9/53 (17%) there were possibilities. These nine blood type incompatible pairs were coupled to nine positive crossmatch pairs, which reflects the efficiency of combining the two categories of donor-recipient combinations into one program. CONCLUSION: The donor kidney exchange program in the Netherlands, in which all seven kidney transplantation centers participated, proved to be a successful program to expand the number of living donor kidney transplantations.

The Dutch national living donor kidney exchange program.

The wait time for deceased-donor kidney transplantation has increased to 4-5 years in the Netherlands. Strategies to expand the donor pool include a living donor kidney exchange program. This makes it possible that patients who cannot directly receive a kidney from their intended living donor, due to ABO blood type incompatibility or a positive cross match, exchange donors in order to receive a compatible kidney. All Dutch kidney transplantation centers agreed on a common protocol. An independent organization is responsible for the allocation, cross matches are centrally performed and exchange takes place on an anonymous basis. Donors travel to the recipient centers. Surgical procedures are scheduled simultaneously. Sixty pairs participated within 1 year. For 9 of 29 ABO blood type incompatible and 17 of 31 cross match positive combinations, a compatible pair was found. Five times a cross match positive couple was matched to a blood type incompatible one, where the recipients were of blood type O. The living donor kidney exchange program is a successful approach that does not harm any of the candidates on the deceased donor kidney waitlist. For optimal results, both ABO blood type incompatible and cross match positive pairs should participate.

Non-heart-beating donor kidneys in the Netherlands: allocation and outcome of transplantation.

BACKGROUND: Since February 1, 2001, kidneys from both heart-beating (HB) and non-heart-beating (NHB) donors in The Netherlands have been indiscriminately allocated through the standard renal-allocation system. METHODS: Renal function and allograft-survival rate for kidneys from NHB and HB donors were compared at 3 and 12 months. RESULTS: The outcomes of 276 renal transplants, 176 from HB donors and 100 from NHB III donors, allocated through the standard renal allocation system, Eurotransplant Kidney Allocation System, and performed between February 1, 2001 and March 1, 2002 were compared. Three months after transplantation, graft survival was 93.7% for HB kidneys and 85.0% for NHB kidneys (P<0.05). At 12 months, graft survival was 92.0% and 83.0%, respectively (P<0.03). Serum creatinine levels in the two groups were comparable at both 3 and 12 months. Multivariate analysis identified previous kidney transplantation (relative risk [RR] 3.33; P<0.005), donor creatinine (RR 1.01; P<0.005), and NHB (RR 2.38; P<0.05) as independent risk factors for transplant failure within 12 months. In multivariate analysis of NHB data, a warm ischemia time (WIT) of 30 minutes or longer (P<0.005; RR 6.16, 95% confidence interval 2.11-18.00) was associated with early graft failure. No difference in 12-month graft survival was seen between HB and NHB kidneys after excluding the kidneys that failed in the first 3 months. CONCLUSION: Early graft failure was significantly more likely in recipients of kidneys from NHB donors. A prolonged WIT was strongly associated with this failure. Standard allocation procedures do not have a negative effect on outcome, and there is no reason to allocate NHB kidneys differently from HB kidneys.