Non-heart-beating Donors Research Articles

The effect of inadequate in situ perfusion in the non heart-beating donor

In situ aortic perfusion in the nonheart-beating donors (NHBD) is an important procedure to reduce primary warm ischaemic injury prior to formal donor organ retrieval. It allows an interim period to obtain donor family consent and theatre preparation. This study describes our experience of inadequate aortic perfusions resulting from difficult aortic cannulations and associated adverse outcome despite reasonable viability tests. Since 1998, all NHBD in our institution are perfused in situ using a double balloon triple lumen (DBTL) catheter inserted through a femoral artery cut-down procedure. The DBTL catheter is positioned with distal occlusive balloon at the aortic bifurcation using the "pull-back" technique, the proximal occlusive balloon lies above the renal arteries. This provides selective aortic perfusion in particular the kidneys. Venous decompression using a femoral vein catheter enables a "two-way infusion system". Pre-transplant viability status of retrieved kidneys is determined by measuring pressure/resistance characteristics to the flow and biochemical markers for ischaemic injury. There were 90 NHBD renal transplants performed from 72 donors. Three renal transplants were carried out from three donors of ineffective in situ perfusion secondary to cannulation difficulties. Femoral cannulation was difficult as a result of extensive atherosclerosis of donor vessels. The comparison of allograft outcome from effective and ineffective in situ perfusion of donors showed high rate of primary nonfunction (PNF) from ineffective perfusion (chi-squared, P < 0.0001). The cases demonstrated poor outcome from ineffective perfusion related to the cannulation difficulties. Therefore a strict policy should be taken in cases where aortic cannulation and perfusion is inadequate, despite pretransplant assessment. In these circumstances, the primary warm ischaemia time should be extended to include this period of ineffective perfusion.

Pancreatic islet cell transplantation using non-heart-beating donors (NHBDs)

Recent dramatic improvements in clinical islet cell transplantation demonstrated by the Edmonton group have increased the demand for this treatment, and donor shortage could become a major problem. Utilization of marginal donors could alleviate the donor shortage, and non-heart-beating donors (NHBDs) might be good resources. The University of Pennsylvania group demonstrated that it was possible to isolate islets from NHBDs, and the group actually transplanted islets from NHBDs, for the first time. The patient became insulin-independent; however, there had been no more cases using NHBDs until our group initiated islet transplantations from NHBDs in Japan. In order to utilize NHBDs effectively, we modified the standard islet isolation method. These modifications included minimizing the warm ischemic time, the use of trypsin inhibition during isolation, carrying out density measurement before purification and the use of a less toxic islet purification solution. With these modifications we were able to transplant nine of ten islet preparations from ten NHBDs (90%), into five type-1 diabetic patients. The first transplantation was performed on April 7, 2004 (the first time in Japan), and this patient became insulin-independent after the second islet transplantation (first time in Japan). All patients showed improved glycemic control and reduced insulin requirements, without hypoglycemic events. We also performed living-donor islet transplantation, with our modified islet isolation protocol, on January 19, 2005. The improved islet isolation protocol enabled us to perform effective islet transplantations from NHBDs, and it also enabled us to perform the living-donor islet transplantation.

Non-heartbeating donors: special considerations for procurement and preservation in liver transplantation

Purpose of reviewThe purpose of this article is to briefly review the current state of the art in the field of organ procurement and preservation as it pertains to non-heartbeating donors, or donation after cardiac death.Recent findingsThe increasing organ shortage and death rate on the waiting list

UW Solution for Hypothermic Machine Perfusion of Warm Ischemic Kidneys

Donation of kidneys from non-heart beating donors (NHBD) is increasingly being used to expand the donor pool. Warm ischemic injury of these kidneys suffered at harvest results in DGF at transplantation. In this study, we used hypothermic continuous machine perfusion preservation to mitigate this injury using two available solutions. Dog kidneys (beagles) were exposed to 0, 60, or 75 min of in situ warm ischemia (37 degrees C), followed by 24 to 72 hr preservation by machine perfusion with Belzer MPS solution or the UW-solution (Viaspan). Auto-transplantation was performed with immediate contralateral nephrectomy. Survival and renal function (serum creatinine) were evaluated for up to 10 days posttransplant. Both solutions were equally effective for 72 hr machine perfusion preservation of dog kidneys giving 100% survival with only minor renal injury. Both solutions were also equally effective for preservation of kidneys exposed to 60 min of warm ischemia. However, only the UW solution gave reliable preservation (86% survival vs. 25% survival) in kidneys exposed to 75 min of warm ischemia and 24 hr machine perfusion. UW solution used with continuous hypothermic machine perfusion preservation can rescue canine kidneys from severe warm ischemic injury.

Potential Suitability for Transplantation of Hearts From Human Non–Heart-Beating Donors: Data Review From the Gift of Life Donor Program

Organ availability limits use of heart transplantation for treatment for end-stage heart disease. Hearts are currently obtained from donors declared brain dead (heart-beating donors [HBDs]). Although use of hearts from non-heart-beating donors (NHBDs) could reduce the shortage, they are considered unusable because of possible peri-mortem ischemic injury. To project how use of NHBD hearts could increase heart donation, we retrospectively reviewed donor databases from the Gift of Life Donor Program (GLDP), our local organ procurement organization, from 2001 through 2003. We screened the NHBD population using conservative donor criteria, assuming an acceptable hypoxic/ischemic time (time from withdrawal of care to cross-clamp) of 30 minutes. During the study period, there were 894 HBDs, 334 heart transplants and 119 NHBDs. NHBDs were similar to HBDs with respect to gender and ethnicity, but NHBDs were proportionately younger. Of 119 NHBDs, 55 did not meet the age criteria (< or =45 years) and 20 were eliminated because of incomplete data. Eighty-two NHBDs were cross-clamped within 30 minutes of care withdrawal. Twenty NHBDs met all cardiac donor criteria, and 14 of these 20 had hypoxic/ischemic times < or =30 minutes. Pro rata estimation for the 20 NHBDs with incomplete data suggested 7 potential additional donors. Based on our assumptions, 12% to 18% of NHBDs in the study period (14 to 21 of 119 total) were potential heart donors, representing a 4% to 6% increase over of the number of heart transplants performed during the same time interval.

Nebulized N-Acetyl Cysteine Protects the Pulmonary Graft Inside the Non–Heart-Beating Donor

The use of lungs from non-heart-beating donors (NHBD) might significantly alleviate the organ shortage. The tolerable warm ischemic period after cardiac arrest, however, is limited to approximately 1 hour. If the lung could be safely protected inside the cadaver, this time period may be prolonged. This would help to obtain family consent and to organize organ retrieval. Pigs (30.8 +/- 0.6 kg) were killed, left untouched for 3 hours, and divided into 3 groups. Nebulized N-acetyl cysteine (NAC) (300 mg), a precursor of the antioxidant agent glutathione, was administered during 10 minutes before death in Group I (NAC-NHBD, n = 6) and 15 minutes after death in Group II (NHBD-NAC, n = 6). In the control group, no aerosol was administered (NHBD, n = 6). After a warm ischemic interval of 3 hours, both lungs in all groups were topically cooled for 1 hour. Thereafter, the left lung was prepared for evaluation in an isolated reperfusion circuit. Hemodynamic, aerodynamic, and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. The right lung was used to measure reduced glutathione (GSH) and oxidized glutathione (GSSG) levels (micromol/g) in lung homogenates and total protein levels in bronchial lavage fluid. Pulmonary vascular resistance, mean airway pressure, and W/D were significantly decreased in NAC-NHBD (1930 +/- 144 Dynes x sec x cm(-5), 14.2 +/- 0.5 cm H2O, and 7.4 +/- 0.4; p < 0.01, 0.01, and 0.05, respectively) and NHBD-NAC (1837 +/- 180 Dynes x sec x cm(-5), 13.3 +/- 1.2 cm H2O, and 7.3 +/- 0.3; p < 0.01, 0.05, and 0.05, respectively) when compared with the control group (5051 +/- 530 Dynes x sec x cm(-5), 17 +/- 0.4 cm H2O, 8.5 +/- 0.1, respectively). GSH/GSSG ratio was significantly higher and protein levels were significantly lower in NAC-NHBD (1.7 +/- 0.1 and 1315 +/- 60 microg/ml; p < 0.05 and 0.05, respectively) and NHBD-NAC (1.7 +/- 0.2 and 1475 +/- 159 microg/ml; p < 0.05 and 0.05, respectively) when compared with the control group (1.2 +/- 0.1 and 2150 +/- 200 microg/ml). Nebulized NAC administered before or shortly after death attenuates early ischemia reperfusion injury via upregulation of glutathione. NAC might be a promising tool to protect the pulmonary graft from both controlled and uncontrolled NHBD.

Non???Heart-Beating Donor Kidneys in The Netherlands: Allocation and Outcome of Transplantation

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. Renal function and allograft-survival rate for kidneys from NHB and HB donors were compared at 3 and 12 months. 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. 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.

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.

The Effect of Normothermic Recirculation is Mediated by Ischemic Preconditioning in NHBD Liver Transplantation

We have evaluated the involvement of hepatic preconditioning mediators (adenosine, adenosine A1 and A2 receptors) during normothermic recirculation (NR) in a model of liver transplantation from non-heart-beating donor (NHBD) pigs. Application of NR after 20 min of warm ischemia (WI) reversed the lethal injury associated with transplantation of NHBD livers (achieving 5-day survival and diminishing glutathione S-transferase (GST), aspartate aminotransferase (AST) and hyaluronic acid (HA)). Adenosine administration prior to WI simulated the effect of NR. Measuring adenosine, we found that during NR, hepatic adenosine levels increased and xanthine levels decreased. Then when we blocked A2 receptors the effect of NR was abolished, whereas the blocking of A1 receptors further protected the liver. Furthermore, A2 blocking improved hepatic perfusion during NR whereas A1 blocking reduced it. The study suggests that NR has a preconditioning effect by maintaining adequate adenosine and xanthine levels. During NR, adenosine protects the liver through A2 activation and damages it through A1 activation although simultaneous stimulation of both receptors exerts a clear beneficial effect. The possible relation of NR mechanism with other preconditioning mediators such as cAMP and nitric oxide synthesis are discussed.

Dual ipsilateral renal transplantation from a non-heartbeating donor

A case is described where both kidneys from non-heart-beating (expanded criteria) donors were dual transplanted ipsilaterally. Although both kidneys passed viability tests on the Newcastle machine preservation system and biomarkers' evaluation, there were logistical issues where the cold ischaemic time was too protracted necessitating the transplantation of both kidneys into one recipient. The recipient had satisfactory outcome with the Cockcroft-Gault creatinine clearance of 72.47 (36.29 ml/min individual kidney glomerular filtration rate) suggesting beneficial use of sub-optimal organs to improve outcome.

Successful outcome following transplantation of an injured liver from a nonheart beating donor

Nonheart beating donation (NHBD) of the liver is a relatively new potential source of grafts. Guidelines to indications and contraindications to donation from controlled nonheart beating donors are still being formulated. We report a successful case of transplantation of a liver from a controlled nonheart beating donor who sustained significant injuries following a road traffic accident. Emergency laparotomy with peri-hepatic packing was performed to control haemorrhage from lacerations in segments VI and VII. Forceful packing resulted in an area of focal ischaemia in segment VI. Trauma to the liver should not be considered an absolute contraindication to controlled NHBD.

Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non-heart-beating kidney transplants

Kidneys from non-heart-beating donors (NHBDs) have high rates of delayed graft function (DGF). Use of calcineurin inhibitors is associated with a reduction in renal blood flow, which may delay graft recovery from ischaemic acute tubular necrosis. To assess whether daclizumab (DZB) could safely replace tacrolimus in the immediate postoperative period, patients were randomized to receive DZB induction and daily mycophenolate mofetil with steroids (DZB group) or standard tacrolimus-based triple therapy (control group). Tacrolimus was given to patients in the DZB group when the serum creatinine level dropped below 350 micromol/l. Fifty-one patients were recruited at two centres over a 2-year interval between 2000 and 2003. The overall rate of immediate function was 28 per cent (13 of 46 grafts), with the highest rate in recipients of machine-perfused kidneys treated with DZB (eight of 15 patients). Induction with DZB and delayed introduction of tacrolimus reduced the incidence of DGF in recipients of machine-perfused NHBD kidneys.

Effective 6-Hour Preservation in Non-heart-beating Donor Canine Lungs with Topical Cooling: Assessment from Histopathological Aspects

This study assesses the possibility of preserving and transplanting non-heart-beating donor (NHBD) lungs under topical cooling for 6 h. The donor dogs were killed and heparinized after cardiac arrest. After 10 min of cardiac massage, the bilateral lungs were deflated. In group 1 (n = 6), the recipient dogs were transplanted and the lungs preserved at 4 degrees C for 6 h. In group 2 (n = 2), the recipients received lungs preserved at room temperature for 4 h. In both groups the right main bronchus, pulmonary artery, and pulmonary vein were clamped and ventilated to examine the lung function. The mean total ischemic time before reperfusion was 7 h 48 min (group 1) and 5 h 55 min (group 2). All dogs in group 1 survived with excellent hemodynamics and gas exchange function. Both dogs in group 2 revealed congestion immediately after reperfusion, and consequently died. We concluded that it is possible to use NHBD lungs for clinical lung transplantation if topical cooling can be initiated soon after irreversible cardiac arrest. Topical cooling of NHBD lungs allows at least 6 h for preparation before transplantation.

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

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.

Use of different immunosuppressive strategies in recipients of kidneys from nonheart-beating donors

In nonheart-beating donor (NHBD) kidney transplants, immunosuppressive management is difficult mainly because of the high incidence of acute tubular necrosis. This has meant that since the start of our NHBD transplant program, several immunosuppression regimes have been used. The aim of this retrospective study was to evaluate the results obtained over 7 years using different treatment protocols. A total of 172 consecutive NHBD transplants performed between April 1996 and December 2002 were treated as follows: G-I (n = 21), cyclosporine (8 mg/kg/day) plus azathioprine plus steroids; G-II (n = 65), low-dose cyclosporine (5 mg/kg/day) plus mycophenolate plus steroids; G-III (n =17), low-dose tacrolimus (0.1 mg/kg/day) plus mycophenolate plus steroids; and G-IV (n = 69), daclizumab plus low-dose tacrolimus plus mycophenolate plus steroids. Delayed graft function rates were 76.2%, 72.3%, 76.5%, and 42%, respectively, for the four groups (P = 0.000). Rejection-free patient rates were 76.2%, 46.2%, 35.3%, and 71% (P < 0.001). Vascular rejection rates were 19%, 30.8%, 52.9%, and 18.8%, (P = 0.025). Two-year graft survival was 71.4% in group I, 95.4% in group II, 94.1 in group III, and 93.8% in group IV (P =0.004). Patient survival was worse in group I (75.2% in group I, 100% in group II, 100% in group III, and 96.7% in group IV at 2 years; P < 0.001). The use of daclizumab and low-dose tacrolimus could be effective at lowering the incidence of delayed graft function in NHBDT, with no negative repercussions on acute rejection.

Liver donation: surgical techniques

Efficient and technically sound graft procurement is an integral component of a liver transplant recipient's immediate and eventual outcome. Furthermore, the current era of organ scarcity increases the demand on the donor surgeon to extract the maximum potential from the existing pool, including the assessment and use of expanded criteria donors, nonheart beating donors, and the splitting of deceased donors to supply 2 recipients. The techniques described here represent the authors' combined experience with over 20 years and 3000 procurements. They are widely applicable to a broad patient population and can be routinely performed at donor hospitals without specialized equipment or staff.

Non-heartbeating organ donation: clinical process and fundamental issues

This case report outlines the clinical process whereby a patient with severe traumatic brain injury became a non-heartbeating organ donor after a withdrawal-of-care decision. This process raises a series of ethical questions regarding decision-making on grounds of futility, the role of the next of kin, informed consent, the accommodation of manoeuvres directed towards organ retrieval at maximal viability, and the timing and determination of death. Although many aspects of the process can be accommodated within fundamental ethical principles and a broad interpretation of the concept of the 'best interests', the variance with established law requires authoritative clarification if a need for transplantable organs is to be responded to without compromising the reputation of practitioners involved in this area of care. Therefore, this recruitment strategy warrants wide public and professional debate to achieve longer-term sustainability and ensure the protection of all parties.

Isoproterenol Reduces Ischemia-Reperfusion Lung Injury Despite β-Blockade 1

If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade. Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP. Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade. The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.

Donor pretreatment using the aerosolized prostacyclin analogue iloprost optimizes post-ischemic function of non-heart beating donor lungs

Background Ischemia-reperfusion injury accounts for one-third of early deaths after lung transplantation. To expand the limited donor pool, lung retrieval from non-heart-beating donors (NHBD) has been introduced recently. However, because of potentially deleterious effects of warm ischemia on microvascular integrity, use of NHBD lungs is limited by short tolerable time periods before preservation. After intravenous prostanoids are routinely used to ameliorate reperfusion injury, the latest evidence suggests similar efficacy of inhaled prostacyclin. Therefore, the impact of donor pretreatment with the prostacyclin analogue iloprost on postischemic NHBD lung function and preservation quality was evaluated. Methods Asystolic pigs (5 per group) were ventilated for 180 minutes of warm ischemia (Group 2). In Group 3, 100 μg iloprost was aerosolized during the final 30 minutes of ventilation with a novel mobile ultrasonic nebulizer. Lungs were then retrogradely preserved with Perfadex and stored for 3 hours. After left lung transplantation and contralateral lung exclusion, hemodynamics, rO 2/F iO 2, and dynamic compliance were monitored for 6 hours and compared with sham-operated controls (Group 1). Pulmonary edema was determined both stereologically and by wet-to-dry weight ratio (W/D). Statistics comprised analysis of variance with repeated measures and Mann-Whitney test. Results Flush preservation pressures, dynamic compliance, inspiratory pressures, and W/D were significantly superior in iloprost-treated lungs, and oxygenation and pulmonary hemodynamics were comparable between groups. Stereology revealed a trend toward lower intraalveolar edema formation in iloprost-treated lungs compared with untreated grafts. Conclusions Alveolar deposition of Iloprost in NHBD lungs before preservation ameliorates postischemic edema and significantly improves lung compliance. This easily applicable innovative approach, which uses a mobile ultrasonic nebulizer, offers an important strategy for improvement of pulmonary preservation quality and might expand the pool of donor lungs.

The long-term outcome of tacrolimus in cadaveric kidney transplantation from non-heart beating donors

Tacrolimus (Tac), developed in 1990, has been applied as an immunosuppressive agent for liver, heart, and kidney transplantation and is known to have more powerful immunosuppressive effects than cyclosporine (CyA). To evaluate the efficacy of Tac in cadaveric kidney transplants from non-heart beating donors, we present the long-term outcome of patients receiving kidneys with ischemic damage, and compared it with that of CyA. Between July 1990 and December 2000, 55 patients with end-stage renal disease received kidneys from non-heart beating donors (Maastrichy category 3) and were treated with Tac and steroid immunosuppressive therapy. During the same period, we also performed 137 non-heart beating cadaveric renal transplants treated with CyA-based immunosuppressive therapy. The patient survival rate was 98% at 1 yr and 96% at 3-10 yr in the Tac group, and 97% at 1-3 yr, 93% at 5 yr and 85% at 10 yr in the CyA group. The graft survival rate was 91% at 1 yr, 80% at 3 yr, 63% at 5 yr and 34% at 10 yr in the Tac group, and 88% at 1 yr, 75% at 3 yr, 63% at 5 yr and 49% at 10 yr in the CyA group. There was no significant difference in either patient or graft survival rates between the two groups. Acute early rejection in the Tac group was less than that in the CyA group but acute tubular necrosis was the same in both groups. This indicates that Tac is available for cadaveric kidney transplants from non-heart beating donors. In conclusion, Tac is available as an immunosuppressive agent even for kidney transplants from non-heart beating donors.