A comparison of the results of renal transplantation from non-heart-beating, conventional cadaveric, and living donors

BACKGROUND: In an attempt to address the shortage of conventional kidney donors, a non-heart-beating donor (NHBD) organ retrieval program has been established. We compared the results of kidney transplants from NHBDs (N = 77) with those from heart-beating cadaveric (HBD; N = 224) and living donors (LD; N = 49), performed in the same eight-year period. METHODS: Patients dying after failed attempts at resuscitation in the accident department or after intracerebral hemorrhage/anoxia were considered as potential NHBDs. After death, in situ kidney perfusion and cooling were achieved using an intra-aortic catheter inserted via a femoral artery cut down. Kidney retrieval and transplant operations were performed using standard techniques. RESULTS: The median (range) warm ischemic time for NHBD kidneys was 25 minutes (5 to 53 min). The initial function rates for NHBD, HBD, and LD transplants were 6.5, 76.3, and 93%, respectively. Primary nonfunction occurred in 5 of 75 evaluable NHBD transplants (7%) compared with only 6 out of 224 (2.7%) HBD and 1 out of 49 (2%) LD transplants (P = NS). Eighty-four percent of NHBD kidney recipients required postoperative dialysis for a median of 19 days. The mean (SD) serum creatinine at 12 months was 179 (73) micromol/L in NHBD kidneys compared with 152 (57) micromol/L for HBD kidneys and 138 (44) micromol/L for LD kidneys. The actuarial five-year graft survival rates for NHBD, HBD, and LD transplants were 79, 75, and 78%, respectively. During the period under study, NHBD organs accounted for 22% of the total renal transplant program. CONCLUSIONS: Despite being associated with poor initial graft function, the long-term allograft survival of NHBD kidneys does not differ significantly from the results of HBD and LD transplants.     

The influence of pulsatile preservation in kidney transplantation from non-heart-beating donors

Continuous hypothermic pulsatile perfusion (CHPP) may offer improved early function compared with cold static perfusion (CSP) for heart-beating cadaveric donors. With an expanding pool of donors, ie, non-heart-beating donors (NHBD), we present our preliminary results with the use of CHPP compared with CSP to preserve kidney grafts retrieved from NHBD. Eighteen consecutive locally procured cadaveric kidneys from NHBD were preserved using CHPP using UW machine perfusion solution in the Life Port kidney transporter. Perfusion parameters were measured serially during pulsatile perfusion. This group was compared with 18 NHBD cadaveric kidneys preserved with CSP. No organs were lost due to faulty technique of preparation or preparation of pulsatile perfusion. Immediate renal function was observed in 13 cases (72.2%). In CSP in NHBD, we had 16 cases with delayed graft function (88.8%). These early results show that the use of pulsatile perfusion to preserve kidneys from NHBD may be associated with improved early outcomes. Longer follow-up is required to answer the more important question as to whether it offers long-term improvements that justify the extra cost and complexity.     

Kidney transplantation from non-heart-beating donors: analysis of organ procurement and outcome

INTRODUCTION: Most donors in Japan have been non-heart-beating donors (NHBD), so-called "marginal donors." In Western countries kidney transplants from NHBD have also been increasing. We analyzed 120 kidneys harvested from NHBD with regard to organ procurement, renal function, graft survival, and the donor factors that affected graft survival. METHODS: Donors were moved into the operating room after cardiac arrest. A double-balloon catheter was inserted into the abdominal aorta via laparotomy. In situ cooling by Euro-Collins solution was started at 500 mL/min. We did not performed cannulation into the femoral artery or vein prior to cardiac arrest. RESULTS: Warm ischemia time (WIT) was 18.6 minutes. Among 108 kidneys (90%) used for transplantation, 102 kidneys functioned. There were no cases of bilateral nonfunctioning kidneys. The delayed graft function (DGF) rate was 86%; however, the death-censored graft survival was 80.0% at 5 years and 62.9% at 10 years. Kidneys implanted after more than 24 hours of total ischemia time required a significantly longer period of hemodialysis. Donor risk factors that affected graft survival included WIT >/= 20 minutes, donor age >/= 50 years, and serum creatinine level at admission > 1.0 mg/dL. CONCLUSIONS: Organ procurement without cannulation prior to cardiac arrest entailed a long WIT and a high DGF rate. However, the graft survival was good. It has been necessary to use grafts from NHBD despite the inherent risk factors. It is important to reduce kidney damage both at the organ procurement and during the posttransplant management.     

Results of islet isolation and their relationship to the clinical outcome of kidney transplantation in cases where both grafts are harvested from the same non-heart-beating donor

Grafts from non-heart-beating donors (NHBDs) are used because of the limited availability of heart-beating brain-dead donors. These grafts sustain ischemic damage, and the severity of this damage varies among different areas of an organ. This study determined whether the results of islet isolation were correlated with the clinical outcomes of kidney transplantations in cases where both grafts were harvested from the same NHBD. Islets we isolated from the pancreata of 23 NHBDs between February 2004 and March 2007. Forty-six kidneys were also harvested from these NHBDs. The recipients of kidney transplants were divided into the successful isolation (n = 14) and failed isolation (n = 32) groups depending on the results of islet isolation. The clinical outcomes of kidney transplantation were compared between the recipients in these two groups. The immediate graft function rate and the 1-year graft survival rate after kidney transplantation in both groups were similar. Hemodialysis after transplantation was required for 6.0 days (SD, 5.2 days) in the successful isolation group and for 12.7 days (13.1 days) in the failed isolation group (p < 0.05). The serum creatinine concentrations at 1, 3, 6, and 12 months after transplantation were elevated in the failed isolation group (p < 0.05). The islet yield was inversely correlated with the requirement of hemodialysis (days) and the serum creatinine level at 1 month after transplantation. However, hemodialysis was required for only 7 days in the recipients of six kidneys that were obtained from NHBDs from whom <40,000 IEQ were obtained (extreme failure of islet isolation). The results of islet isolation were found to correlate with the kidney function after transplantation when both grafts are harvested from the same NHBD. However, the marginal conditions of NHBDs affect the results of islet isolation more than they do the posttransplantation kidney function.     

Transplantation of kidneys harvested from non-heart-beating donors: early and long-term results

Abstract  The purpose of this retrospective study was to evaluate results of non-heart-beating donor (NHBD) kidney transplantation. Between Jan 1986 and Dec 1994,80 out of 582 cadaveric kidneys were harvested from NHBD (31.9 min ± 24 after cardiac arrest). The results in the NHBD group (76 recipients) were compared with those obtained after transplantation of kidneys harvested from heart-beating donors (HBD) with respect to early graft function, and the graft and recipient's survival. Both groups were matched for sex, age, PRA level, number of HLA mismatches, and cold ischemia time. Triple immunosuppression therapy was used in both groups. Acute tubular necrosis (ATN) was observed significantly more frequently in the NHBD group (50 of 76 recipients vs 33 of 100 in the HBD group). The striking finding of this study was that the occurrence of primary non-function was the same in both groups and that the main cause of it was acute rejection. The 1-year patient and graft survival rates were 98.7 % and 81.6 % for the NHBD group and 99 % and 90 % for the HBD group, respectively. There was also no statistical difference in the serum creat-inine concentration in both groups. We concluded that despite an increased incidence of ATN in the NHBD kidney recipients, the long-term results are good and comparable with those in the HBD group.     

Renal transplantation from non-heart beating donors: a promising alternative to enlarge the donor pool

The aim of this study was to compare the survival and midterm function of kidneys from non-heart beating donors (NHBD) with those of kidneys from heart beating donors (HBD). From 1989 to 1998, 144 kidneys were procured from NHBD at the Hospital Clínico San Carlos in Madrid, of which 95 were transplanted. The kidney grafts were maintained from the moment of the diagnosis of cardiac arrest until the time of procurement by cardiopulmonary bypass. There was no significant difference in renal function and the number of rejection episodes between the NHBD and HBD transplants. The NHBD kidneys showed a 5.73-fold increase in the incidence of delayed graft function (adjusted relative risk 95% confidence interval, 2.82 to 11.62). One- and five-year survival rates for NHBD grafts were 84.6 and 82.7%, respectively, compared with 87.5 and 83.9% for HBD (P = 0.5767). Cox analysis showed that the predictive factors for worse NHBD graft survival were type of NHBD donor and the occurrence of corticoresistant rejection. Ninety of the NHBD organs were procured from subjects suffering irreversible cardiac arrest on the street who were transferred to our center for the sole purpose of donation. Fifty-four of these kidneys were transplanted and all showed primary function. When a strict protocol is adhered to, the outcome of renal transplant from NHBD compares well with that from HBD. It is believed that the high number of organs obtained from subjects undergoing irreversible cardiac arrest on the street might encourage the adoption of new criteria for the management of this type of pathology with the ultimate goal of kidney donation.     

Long-term renal function in kidneys from non-heart-beating donors: A single-center experience

BACKGROUND: Cadaveric kidneys from brain-stem-dead donors continue to be limited because the number of donors has reached a plateau. Wide recruitment of non-heart-beating donors (NHBD) could significantly increase the donor pool. NHBD renal transplants are underused because of the concern of poor quality graft function from such donors. In response to this perception, we reviewed 46 NHBD renal transplants performed in our center since 1998. METHODS: All NHBD kidneys were machine-perfused using the Newcastle continuous-hypothermic pulsatile preservation system before transplantation. A control heart-beating-donor (HBD) group was taken as the next consecutive HBD renal transplant to the NHBD transplant. The outcome and quality of function of the groups of renal transplants were analyzed for short-term and long-term performance. RESULTS: The renal transplant patients were matched for donor and recipient factors. Survival rates for allografts and patients were similar for 1 to 3 years. There was an increased incidence of delayed graft function in the NHBD renal transplants in the perioperative period. The creatinine clearance was 22.8+/-2.3 mL/minute for NHBD patients and 44.4+/-2.9 mL/minute for HBD patients at the time of discharge from hospital. This difference equalized after 3 months and the creatinine clearance for NHBD was 44.2+/-2.4 mL/minute and for HBD 49.2+/-3.4 mL/minute. CONCLUSIONS: Our results for NHBD renal transplants confirm that such grafts suffer primary warm ischemic injury, shown by the increased incidence of acute tubular necrosis and consequent delayed graft function. This produced poor renal function at the time of hospital discharge. After 3 months, the renal function of NHBD cases improved to the level seen in HBD patients.     

Kidney transplantation from non–heart-beating donors: a Spanish view

All over the world, the waiting list and waiting time for transplant will inevitably become longer as the demand for kidneys continues to exceed the supply. Although there is a need to extend the use of brain-dead donors with heartbeats, there is still room for additional sources of organs, and this has prompted the use of the non–heart-beating donor (NHBD). The viability of the kidney from the NHBD, which is invariably subjected to a period of warm ischemia, is the most crucial factor for transplant outcome. However, in our experience, by applying a strict warm ischemia protocol and carefully managing the donor, the percentage of non-functioning grafts is low. The results presented in terms of graft survival and mid-term renal function with NHBD are encouraging and comparable to those related to the use of kidneys from young heart-beating donors. Based on these data, NHBDs should not be considered suboptimal, since other marginal donors such as elderly donors, for instance, have resulted in worse outcomes. In our experience, the NHBD kidney is an extremely useful contribution to the donor pool, and its use has allowed us to increase the total number of kidney transplants performed and, as consequence, to decrease the waiting list.     

Expanding the donor pool: use of renal transplants from non-heart-beating donors supported with extracorporeal membrane oxygenation

Abstract:  In response to organ shortage, we used the renal grafts from non-heart-beating donors (NHBDs). Extracorporeal membrane oxygenation (ECMO) was used to maintain NHBDs before organ procurement. We compared the results of renal transplantation from different donors, including heart-beating donors (HBDs), living-related donors (LDs), and NHBDs supported with ECMO. From February 1998 to June 2003, we recruited 219 patients receiving renal transplantation at National Taiwan University Hospital. Among them, 31 received kidneys from NHBDs supported with ECMO, 120 from HBDs, and 68 from LDs. Multiple organ transplant recipients were not included in this study. We compared the graft survival, serum creatinine levels, and estimated glomerular filtration rates of the three groups. The rate of delayed graft function was higher in NHBD recipients (41.9%) than in HBD recipients (27.0%) and LD recipients (10.9%) (p = 0.003). In the NHBD group, the recipients of grafts with delayed function had significantly longer ECMO runs (63.1 ± 3.0 min) than those without delayed function (53.7 ± 2.5 min) (p = 0.024). Estimated glomerular filtration rate (p = 0.472) and mean serum creatinine level (p = 0.286) were not significantly different between the three groups using a longitudinal approach. The 5-yr graft survival rates for NHBD (88.4%, 95% CI: 0.680–0.962), HBD (83.2%, 95% CI: 0.728–0.899), and LD transplant recipients (89.3%, 95% CI: 0.619–0.974) were not significantly different (p = 0.239). The 5-yr patient survival rates for NHBD, HBD, and LD transplant recipients were 100, 93.0 (95% CI: 0.859–0.966) and 100% respectively. The long-term allograft survival and function of kidneys from NHBDs supported by ECMO, HBD, and LD did not differ significantly. Long ECMO running time tended to delay graft function.     

Dual renal transplantation for kidneys from marginal non-heart-beating donors

Kidneys transplanted from non-heart-beating donors (NHBD) are generally regarded as marginal or extended criteria grafts due to the associated period of warm ischemia. The most prolonged periods occurring in the category II (uncontrolled) donor. This potential for injury can adversely affect the glomular filtration rate (GFR), which in severe cases results in primary nonfunction. Viability testing can identify a group of kidneys that, although unsuitable for solitary transplantation, may be considered for dual transplant. This retrospective study examined a series of 11 dual renal transplants, comparing 3- and 12-month GFR outcome data with 81 single NHBD transplants. The mean GFR at 3 months in the dual group was 47.6 and at 12 months was 48.6. In the single group the GFR at 3 months was 40.6 and at 12 months was 41.9. Thus using viability testing to identify NHBD kidneys suitable for dual transplant appears reliable and predictable.     

Why did it take so long to start a non-heart-beating donor program in Belgium?

The first cadaver kidney transplant, performed in June 1963 in Belgium, was from a heart beating donor (HBD). It was the first ever in the world. Since that period, almost all cadaver organs were procured from brain death donors. When the Belgian law on organ donation and transplantation was published on February 1987, with its opting-out principle, no emphasis was placed on procuring organs after cardiac death. Based on the Maastricht experience, in the early nineties, the transplant community interpellated the National Belgian Council of Physicians to facilitate organ procurement in Non-Heart-Beating Donors (NHBD) following the law. But, the transplant community had to wait for the impulse of the first International Congress on NHBD in 1995,where the 4 categories of Maastricht NHBD were defined. It also published 12 Statements and Recommendations which were eventually approved by the European Council. Then all local Ethical Committees received queries for approving local NHBD programs. Almost all centres requested viability testing assessment of the NHBD organ prior to implantation, and proposed the introduction of machine perfusion technology. Finally, all centres joined their efforts and made a collaborative agreement with Organ Recovery Systems for a 24/7 machine perfusion service from a central laboratory. During a three year period (2003-2005), 46 NHBD kidneys were recovered. Among these kidneys, 32 were perfused in the Organ Recovery Systems central laboratory. The Delayed Graft Function (DGF) rate for these perfused kidneys was 25%. Only one graft was lost in this subgroup. Livers, pancreases (for islet preparation) and lungs (for experimental ex-vivo evaluation) were also recovered from these non-heart-beating donors.     

Immunosuppresive agents have an influence on ischemia-reperfusion injury in kidneys procured from a non-heart-beating donor: experimental study

Ischemic-reperfusion injury (IRI) has a considerable influence on the function of kidneys from non-heart-beating donors (NHBD) after transplantation. IRI is accompanied by a marked inflammatory reaction with the production of reactive oxygen species and of the proinflammatory cytokine tumor necrosis factor α. The effect on the development of ischemic-reperfusion injury of early treatment of the donor with mycophenolate mofetil and tacrolimus was monitored in an animal model of a NHBD. The study demonstrated that the combination of the two immunosuppressives reduced the production in the NHBD kidney of tumor necrosis factor α, an indicator of the degree of inflammatory reaction after reperfusion, to a considerable extent but not of malondialdehyde or reduced glutathione. Pre-treatment of marginal donors with these immunosuppressants may improve the immediate function of transplanted kidneys by reducing cytokine production.     

Development of a non-heart-beating donor program and results after the first year

Our lung transplant unit began activity in October 2008. We have performed 37 lung transplants with a hospital mortality of 2.7% (n = 1). The need for a greater number of donors and the presence of an already existent non-heart-beating donor (NHBD) program for abdominal grafts and tissues encouraged us to consider assessing lung grafts from these donors. It was necessary to develop a new multiorgan preservation methodology, “bithermia preservation.” The clinical experience with which during the first year June 2010 to July 2011, including 15 NHBDs is presented herein. The chest x-ray was normal in 6 donors (40%) and 7 had pulmonary infiltrates. Bronchoscopy was normal in 8 donors (53%) but 3 had abundant bleeding airway secretions and signs of bronchoaspiration. Preservation procedures were performed in 6 donors. Pulmonary functional evaluation in 4 donors showed gas measurements to be adequate in 75% of cases. Three double-lung grafts were judged to be valid for implantation, among which we performed 3 lung transplantations, 1 bilateral and 2 unilaterals, while 2 grafts were offered to the National Transplant Organization for other units. No transplant suffered primary graft dysfunction; all 3 showed excellent function allowing early extubation in 2 cases. There was no in-hospital mortality. All 3 patients are alive and leading normal lives; none has bronchiolitis obliterans syndrome. In conclusion, the “bithermia preservation” methodology achieved adequate lung preservation in NHBDs, allowing liver, kidneys, and lungs to be obtained from the same donor.     

Diabetic donors as a source of non-heart-beating renal transplants

Due to the organ shortage, many renal transplantation centers attempt to increase the donor pool by using non-heart-beating donors (NHBDs). These kidneys are generally regarded as "marginal" grafts. Many centers do not consider transplantation from an NHBD with a history of diabetes as it is a more suboptimal donor. We began our NHBD program in 1998 and have performed 5 renal transplants from diabetic NHBDs. Viability testing identified kidneys suitable for single or dual transplantation. Although kidneys from brain stem dead donors with diabetes have been used successfully, our data suggested that kidneys from diabetic NHBDs can also be used although we still need long-term results.     

Renal transplantation from non-heart-beating donors: a single-center 10-year experience

BACKGROUND: Reluctance to accept non-heart-beating donors (NHBD) as a source of kidneys, is due to medical, ethical, and logistical reasons. Evidence suggest that the short-term graft survival is similar to that of kidneys obtained from heart-beating donors (HBD). However, few studies, with long-term follow-up are available. We conducted a single-center study of kidneys obtained from NHBD, in a 14-year period. METHODS: We studied 100 patients transplanted with kidneys between 1989 and 2004, using NHBD, supported by heart compression and mechanical ventilation (n = 24), intravascular in situ cooling (n = 59), or cardiorespiratory resuscitation plus manual abdominal counterpulsation without cooling (n = 17), the last technique being used from 1998. The median follow-up was 51 +/- 51 months (range, 1 to 170). The outcomes of these procedures were compared to those of 1025 transplantations of kidneys from HBD performed during the same period. RESULTS: The characteristics of the recipients did not differ significantly between the two groups. Kidneys from NHBD showed a significantly higher rate of delayed graft function (DGF; 84% vs 26%; (P < .001), furthermore, the primary nonfunction (PNF) incidence was significantly higher with NHBD vs HBD (16% vs 10%; P < .001). The incidence of acute rejection episodes (ARE) within 3 months and at 1 year did not differ between the groups of donors; however, more NHBD kidneys were lost from ARE. The short-term (3-month and 1 year) and long-term (5 and 10 years) renal function, determined by the serum creatinine levels, and patient and graft survival were not different for kidneys obtained from NHBD. CONCLUSIONS: The incidences of PNF and DGF were significantly higher with NHBD, which produced poorer renal function at the time of hospital discharge. One-, 5-, and 10-year graft survivals and renal function did not differ between NHBD and HBD grafts. In our series, PNF was the main barrier to the use of NHBD.     

Ethical and legal issues in non-heart-beating organ donation

Procurement of kidneys and livers from non-heart-beating donors (NHBD) raises ethical and legal issues that need to be considered before wider use of these donors is undertaken. Although NHBDs were used in kidney transplantation as early as the 1960s, retrieval of these organs is not universally accepted today. From a medical point of view, these organs were considered "marginal" because the majority showed delayed or impaired function early after implantation. Legal problems relate to determination of death on cardiopulmonary criteria, the issue of valid consent, and the use of preservation measures. Among ethical issues involved are observance of the dead-donor rule, decisions with respect to resuscitation and withdrawal of life-sustaining treatment, respect for the dying patient and the dead body, and proper guidance of the family. In The Netherlands NHB donation was pioneered by the Maastricht Centre as early as 1981. Today, all seven transplant centers procure and transplant these organs, and NHBDs have become an important source of transplantable kidneys and livers. Recent legislation in The Netherlands also supports NHB donation by allowing the use of organ-preserving measures, even in the absence of family consent. As a result, one of every three kidneys transplanted in The Netherlands in 2004 derives from a NHBD. This article explores Dutch NHBD practice, protocols, and results and compares these data internationally.     

Renal transplantation from non-heart- beating donors: a review of the European experience

Shortage of organs for transplantation has prompted a few centers in Europe to retrieve kidneys from non-heart-beating donors (NHBD). Indeed, it has been suggested that NHBDs could bridge the gap between supply and demand in renal transplantation. However, NHB donation still has only limited diffusion. Reluctance to accept NHBDs as a source of kidneys is due to medical, organizational and ethical reasons. The experiences, protocols and results in Europe are described in this review. The analysis of the European experience of kidney transplantation from NHBDs looks promising in term of results. Long-term outcome is very similar in the two groups notwithstanding worse short-term results. Actually, the primary non functioning of grafts is significantly worse in NHBD kidneys. However, data suggest that results could be improved by better patient selection and retrieval team organization. Delayed graft function is also much more frequent in NHBD kidneys; this poses problems in the short-term, but in the long-term does not seem to influence the outcome. The risk that efforts in NHBD programs endanger regular HBD programs because of limited organizational resources is not supported by published data. Indeed, in the experiences analysed here it appears that NHBD consistently increased the number of available kidneys and has no effect on HB donations.     

Kidney transplantation with grafts from non-heart-beating donors

We analyzed the function and outcome of 16 kidney transplants performed in our hospital from non-heart-beating donors who were harvested at other hospitals. The cold ischemia times were longer and the delayed graft function rates higher. However, graft function was no different from that of kidneys from heart-beating donors. This experience has encouraged us to use this type of donor to reduce the transplant waiting list.     

Work-load generated by the establishment of a non-heart beating kidney transplant programme

The work-load generated by a non-heart-beating donor (NHBD) kidney transplant programme over a 3-year period is reported. A total of 73 referrals were made, 64 from the Accident department and 9 from the wards. Organ procurement was performed in 24 cases (33%) and resulted in the retrieval of 44 kidneys. Reasons for failure to achieve organ procurement were: refused consent (n=13; 18%), relatives unavailable to ask for consent (n=9; 12%), technical problems with catheter insertion or perfusion (n=10; 14%), transplant staff unavailable (n=1; 1%), long asystolic period (n=8; 11%) and donor unsuitable for other reasons (n=8; 11%). Of the 44 kidneys retrieved, 30 were transplanted locally, 8 were transplanted at other United Kingdom centres and 6 were discarded. Locally transplanted NHBD kidneys represented 21% of the total transplant programme during the time period under study. We conclude that NHBD kidneys are a good source of additional organs for transplantation, but only one-third of referrals result in a successful procurement procedure. Moreover, the setting up of a successful programme is labour-intensive and requires a highly committed staff.