Successful 48-h liver preservation by controlling nutritional status of donor and recipient

Abstract The nutritional status of the donor has been shown to affect the outcome of liver transplantation in the rat. It has been proposed that this may be due to inhibition of Kupffer cell induced injury to the reperfused organ, which leads to an inflammatory type response. In this study we investigated how altering the nutritional status of the recipient affects the outcome of liver transplantation after preservation of the liver for 44 or 48 h in the University of Wisconsin (UW) solution. The nutritional status of the rats was altered by either fasting or by feeding an essential fatty acid free diet (EFAD) for 2 months. This type of diet has been shown to reduce significantly the inflammatory response in rats. Survival after 44-h preservation of livers from fed donors (fed a standard laboratory diet) transplanted to fed recipients was 29% (2/7) but increased to 80% (4/5) when the recipient was fed the EFAD diet. After 48-h preservation, there were no survivors under either of these two dietary combinations. However, survival was 100% after 48-h preservation if the donor had been fasted for 4 days and the recipient was fed the EFAD. These results showed that the nutritional status of the donor and recipient are important factors in the outcome of liver transplantation. How nutritional factors affect liver preservation and transplantation are not clear but may be related to the inflammatory response regulated by Kupffer cells and circulating neutrophils in the liver, both of which are influenced by the diet of the animal.     

Evidence that both cyclosporin and azathioprine prevent warm ischemia reperfusion injury to the rat liver

The present work was undertaken to study whether the immunosuppressive agents cyclosporin (CyA) and azathioprine (AZA) ameliorate hepatic injury after warm ischemia. A temporary, normothermic liver ischemia was induced in female Sprague-Dawley rats. The rats were treated with CyA (10 mg/kg per day p.o.), AZA (8 mg/kg per day p.o.), or vehicles for 4 days before surgery. Seven-day survival rates after 60 min of ischemia improved significantly with CyA (76.2%, P<0.005) and AZA (78.6%, P<0.001) treatment, compared with 43.0% for the control group. The highest levels of serum aminotransferases in the treatment groups tended to be lower than those in the control group. The peak values for the percentage of liver necrosis, an indicator of the extent of hepatic necrosis, in the animals treated with CyA (26.1%±7.2%, mean±SEM) and AZA (32.1%±5.7%) were significantly lower than in the control group (47.4%±3.7%). Lipid peroxidative damage after reperfusion, assessed as the hepatic malondialdehyde (MDA) concentration, was significantly suppressed by pretreatment with CyA and AZA. Histological findings coincided with other parameters. This study demonstrates that both AZA and CyA have beneficial effects on normothermic liver ischemia in rats. It is suggested that the diminished lipid peroxidative damage with these agents might be one of the mechanisms responsible for this.     

Ischemia–reperfusion injury as the leading cause of primary non-function in renal transplantation using donors with prolonged warm ischemic time

Abstract:  Renal transplantation (RTx) from marginal donors has been performed in most Japanese transplant centers because of severe donor organ shortage. RTx using marginal donors with prolonged warm ischemic time (WIT) has sometimes resulted in primary non-function (PNF). Among 53 cadaveric RTx performed at Kanazawa Medical University between October 1986 and May 2006, five cases using non-heart-beating donors resulted in PNF. In these five patients, histologic examination of one h RBx (graft biopsy one h after revascularization) revealed extensive congestion in glomerular and peritubular capillaries. Glomerular subendothelial swelling and mesangiolysis were also detected, and electron microscopic examination showed widening of the subendothelial spaces of glomerular capillaries. Such findings of endothelial damage were not detected in the other 48 cases without PNF. In contrast, no distinct abnormalities other than acute tubular necrosis were found in zero h RBx (graft biopsy before implantation) obtained from three patients with PNF. Prolonged WIT was the prominent feature of the five patients with PNF, and multiple logistic analysis showed that prolonged WIT was a significant risk factor for the development of endothelial damage on reperfusion. Paired allografts from the same donors of these five cases also ended in PNF. It is conceivable that the endothelial damage was caused by ischemia–reperfusion injury and extensive congestion followed as a result of endothelial injury. Ischemia–reperfusion injury is the leading cause of PNF in RTx using donors with prolonged WIT. Guidelines to assess the viability of marginal grafts should be established in the future to prevent transplantation of non-functioning grafts.     

Inhibition of rat heart allograft rejection by a PUVA treatment of the graft recipient

Treatment of rat heart grafts with PUVA, the combination of the photosensitizer 8-methoxypsoralen and longwave ultraviolet light, leads to a prolonged transplant survival in allogeneic recipients. A PUVA treatment of the recipient rats, performed for 7 consecutive days after transplantation, prolonged graft survival even more effectively. This may be due to the systemic immunomodulatory effects of PUVA in the recipient. One of the mediators is urocanic acid, which is transformed by ultraviolet light in the skin from its trans- to the cis-isomer, which, in turn, acts as a mediator on the immune system. An injection of cisurocanic acid into graft recipients for 7 consecutive days after transplantation resulted in prolonged graft survival; in 40% of the rats, permanent graft acceptance was observed. The significance of these results for clinical organ transplantation is discussed.     

The protective mechanism of magnolol,a Chinese herb drug,against warm ischemia-reperfusion injury of rat liver

BACKGROUND: Cell apoptosis following warm ischemia-reperfusion injury is a major concern in clinical issues such as organ transplantation, trauma, and cardiogenic shock. The purpose of this study was to evaluate the possible role of magnolol, a Chinese herb drug, in apoptotic injury and the kinetic expression of apoptotic-related genes in rat livers subjected to warm ischemia-reperfusion (WI/R). MATERIALS AND METHODS: Three weeks prior to the experiment 10 rats underwent a portosystemic shunt operation according to Bengmerk's method. The rats were divided into three groups. Group 1 (GI) was the control group, Group 2 (GII) and Group 3 (GIII) the magnolol-treated groups. GI and GII were subjected to 2 h and GIII to 3 h of WI/R by clamping the portal vein and hepatic artery under ether anesthesia. RESULTS: Results show that all the control rats died after 2 h WI/R. Apoptotic cells were detected under microscopy as well as by DNA assay. Magnolol-treated groups tolerated warm ischemia-reperfusion for 2 h and significantly less apoptotic cells were observed (198 +/- 22 vs 42.6 +/- 28). But magnolol-treated rats could not tolerate 3 h warm ischemia-reperfusion. RT-PCR of liver tissue shows that there is an upregulated expression of the anti-apoptotic Bcl-xL gene and suppression of the Bcl-xS gene in GII. CONCLUSION: Magnolol has an anti-apoptotic effect and protects the liver against WI/R for 2 h but not for 3 h through upregulation of the anti-apoptotic Bcl-XL gene and suppression of the Bcl-xS gene.     

Intermittent capillary perfusion in rat pancreas grafts following short- and long-term preservation in University of Wisconsin solution

In pancreas transplantation (PTx), ischemia/reperfusion-induced deterioration of graft-microcirculation is accompanied by alterations of intermittent capillary perfusion (IP; alternating cessation and resumption of capillary blood flow) is known to counteract malperfusion. Incidence and effectiveness of IP following short- versus long-term preservation of pancreas grafts with University of Wisconsin (UW) solution has not been examined so far. PTx was performed in Lewis rats following 2-h or 18-h preservation in UW solution. Using intravital fluorescence microscopy, functional capillary density (FCD), red blood cell (RBC) velocity, IP-incidence and -frequency were analyzed. Laser Doppler flowmetry allowed for the determination of erythrocyte flux and velocity. Measurements were performed at 30, 60 and 120 min after reperfusion. Nontransplanted animals served as controls. FCD, RBC-velocity and -flux remained unchanged in the 2-h group. IP was encountered in 87% of all observation areas at 120 min. After 18-h ischemia, FCD was significantly reduced, which was paralleled by a 50% incidence of IP at 120 min. Tissue edema and leukocyte infiltration in pancreas grafts following 18-h preservation were significantly enhanced. Therefore, IP is an important mechanism aimed at improving microcirculation and UW solution is suitable to preserve vasomotion-activities enabling long-term preservation in a pancreas graft.     

大鼠移植肝GHR和IGF-1R的变化及热缺血损伤和外源性GH治疗的影响

目的探讨肝移植术后GHR和IGF-1R的变化及热缺血损伤和外源性GH治疗的影响。方法建立大鼠原位肝移植模型,分为肝动脉结扎组、0 min热缺血组、10 min热缺血组和10 min热缺血+rhGH治疗组,采用放射配体结合分析法检测肝移植术后1、4、7 d移植肝GHR和IGF-1R表达和亲和力改变,检测术后1、3、57、d血清ALT,并观察组织病理学变化。结果0 min热缺血组术后7 d移植肝组织GHR数和IGF-1R数明显降低(P<0.05),10 min热缺血组术后1、4、7 dGHR数分别为25.9±3.5、27.5±2.8、17.8±3.4,IGF-1R数分别为13.9±2.1、12.8±2.0、12.2±2.3,与0 min热缺血组相比差异有显著性(P<0.05),ALT峰值升高,肝功能恢复延迟,组织病理学表现损伤加重;10 min热缺血+rhGH治疗组术后7d GHR数恢复明显,术后4、7 d IGF-1R数恢复明显(P<0.05),ALT恢复加快,术后3、57、d均明显下降(P<0.05),组织病理学表现损伤恢复加快。结论肝移植术后7 d内GHR和IGF-1R呈下降趋势,10 min热缺血损伤导致GHR和IGF-1R减少,应用外源性GH可促进GHR、IGF-1R数和10 min热缺血移植肝损伤恢复。     

The pancreas allograft donor: current status,controversies, and challenges for the future

Fridell JA, Rogers J, Stratta RJ. The pancreas allograft donor: current status, controversies, and challenges for the future.
Clin Transplant 2010: 24: 433–449.
© 2010 John Wiley & Sons A/S. Abstract: The pancreas allograft is a scarce resource that is currently underutilized. The selection of appropriate deceased donors for pancreas procurement is of paramount importance for minimizing technical failure and optimizing long‐term outcomes in pancreas transplantation. Despite the increasing demand for pancreas transplantation, increases in overall organ donation rates and the evolution of criteria that constitute an “acceptable” pancreas donor, the number of deceased donor pancreas transplants being performed in the United States has actually declined in recent years. Although there are many factors that must be considered during evaluation of the potential pancreas allograft donor to minimize morbidity and graft loss, it is evident that there are transplantable organs that are not used. In this review, deceased donor pancreas identification, management, selection, allocation, assessment, preservation, and the problem of pancreas underutilization will be discussed.     

A newly developed hydroxyl radical scavenger,EPC-K1 can improve the survival of swine warm ischemia-damaged transplanted liver grafts

Using a swine orthotopic liver transplantation (SOLTx) model, we assessed the effect of a new hydroxyl radical scavenger EPC-K1 on warm ischemic damage of the liver graft and recipient survival. Animals were divided into 5 groups. The first group (control group 1) consisted of 5 pigs which were not operated on but served as controls for the indocianine green disappearance rate (K-ICG) determinations. In the second group (control group 2), 10 livers were transplanted without warm ischemia (WI) and the K-ICG values were measured. The third group (control group 3) was the main control group for the study groups and consisted of 5 liver transplants with 30 min of WI without any special treatment. The fourth and fifth groups served as study groups 1 and 2. Five transplants were carried out in each group, as in control group 3. In study group 1 recipients were treated with an additional 5 mg/kg i. v. EPC-K1 and in study group 2 with 20 mg/kg i. v. EPC-K1. Significant improvement in glutamic oxaloacetic transaminase (GOT) and lactate dehydrogenase (LDH) levels, K-ICG values and histological findings were observed in the EPC-K1 treated groups. The intravenous administration of this agent had a strong protective effect on warm ischemic damage after 30 min of WI and could significantly prolong the graft and recipient survival.     

Preservation injury and acute rejection of rat intestinal grafts: Protection afforded by pyruvate

Pyruvate has been shown to prevent intestinal mucosal injury after ischemia-reperfusion. The aim of the present study was to determine whether pyruvate can (1) prevent postreperfusion mucosal injury occurring after intestinal preservation and subsequent transplantation and (2) exert a protective effect on the intestinal graft mucosa during acute rejection. Preservation mucosal injury was evaluated, after 2 hours of reperfusion, by comparing grafts transplanted in a rat syngeneic combination (ACI to ACI) after 2 hours of cold preservation using pyruvate (n = 6) or placebo (n = 6). Mucosal parameters obtained during acute rejection (allogeneic combination: ACI to Lewis) were compared between placebo-treated (n =6) and pyruvate-treated (n = 6) animals. Tissue injury was evaluated by histopathologic examination, oxygen free radical production by luminol-enhanced chemiluminescence, and degree of neutrophil infiltration by myeloperoxidase staining. After reperfusion of the preserved grafts and during acute rejection, mucosal oxygen free radical levels and the number of infiltrating neutrophils were significantly (P <0.05) increased in the untreated grafts, whereas there was a statistically significant inhibition of these parameters in those treated with pyruvate. Mucosal injury, seen after reperfusion of the preserved grafts, was prevented by pyruvate. The histopathologic abnormalities observed in the untreated grafts during rejection were also significantly reduced by pyruvate. Treatment with pyruvate before cold preservation of intestinal grafts, in this rat model, reduced reperfusion mucosal injury, neutrophil infiltration, and oxygen free radical production. Oxygen free radicals were produced in the mucosa of the graft during acute rejection and their production was reduced by pyruvate, which exerted a protective effect on the rejecting allograft mucosa.     

尸体供者小肠、肝和肾脏器联合切取及保存技术

目的建立尸体供者全腹腔脏器切取和保存技术,同时为不同的小肠移植、肝移植和肾移植受者提供供器官。方法共进行8次同一尸体供者的全腹腔脏器切取手术。供体切取经腹主动脉与肠系膜下静脉插管,高渗枸橼酸-腺苷肾保存液及UniversityofWisconsin液原位灌注,肝、小肠、胰腺、脾、肾整块切取。供器官经后台修整后,分别成为肝、小肠和肾移植物进行相应的受者移植手术。结果 8次供者腹腔脏器切取和后台修整手术共获取8具小肠移植物、8具肝移植物和16具肾移植物。利用所修整出的供器官成功地完成5次单独小肠移植、8次肝移植和16次肾移植,术后移植物功能良好。结论所建立的尸体供者全腹腔脏器切取和保存技术,可同时为不同的小肠移植、肝移植和肾移植受者提供供器官;借鉴美国匹兹堡大学的供者器官后台分离技术,还可同时为胰腺移植受者提供供器官。     

Repopulation of donor heart by recipient bone marrow-derived dendritic cells prior to transplantation causes acute rejection by both the allogeneic and syngeneic recipient

Experimental studies on allogeneic transplantation have shown that recipient dendritic cells (DC) play a role in peripheral tolerance as well as in rejection of allografts. It is not known whether DC exert their tolerogenic function in recipient lymphoid tissue, and whether they process shed alloantigen in the graft itself. To answer this question we created a chimeric heart model deprived of its own DC and repopulated by recipient DC. The rationale for this model was to observe whether recipient DC located in the graft attenuate recruitment and stimulation of recipient lymphocytes, subsequently prolonging graft survival. Vascularized bone marrow transplants (VBMTx) from the prospective recipient to the lethally irradiated heart donor, which function for a period of 14 days, were used to replace donor DC with prospective recipient DC. Hearts from chimeric LEW rats (with BN DC) were transplanted to untreated BN rats. Also, hearts from chimeric LEW rats (with BN DC) were returned to untreated LEW rats. Replacement of the donor heart with recipient DC did not prolong graft survival. Rather, it initiated a rejection reaction that was already present in the donor. Recipient DC retained their immunogenic properties also when the graft was returned back to a donor strain animal.     

Human liver stem cell-derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia

Livers from donors after circulatory death (DCD) are a promising option to increase the donor pool, but their use is associated with higher complication rate and inferior graft survival. Normothermic machine perfusion (NMP) keeps the graft at 37°C, providing nutrients and oxygen supply. Human liver stem cell-derived extracellular vesicles (HLSC-EVs) are able to reduce liver injury and promote regeneration. We investigated the efficacy of a reconditioning strategy with HLSC-EVs in an experimental model of NMP. Following total hepatectomy, rat livers were divided into 4 groups: (i) healthy livers, (ii) warm ischemic livers (60 min of warm ischemia), (iii) warm ischemic livers treated with 5 × 10⁸ HLSC-EVs/g-liver, and (iv) warm ischemic livers treated with a 25 × 10⁸ HLSC-EVs/g-liver. NMP lasted 6 h and HLSC-EVs (Unicyte AG, Germany) were administered within the first 15 min. Compared to controls, HLSC-EV treatment significantly reduced transaminases release. Moreover, HLSC-EVs enhanced liver metabolism by promoting phosphate utilization and pH self-regulation. As compared to controls, the higher dose of HLSC-EV was associated with significantly higher bile production and lower intrahepatic resistance. Histologically, this group showed reduced necrosis and enhanced proliferation. In conclusion, HLSC-EV treatment during NMP was feasible and effective in reducing injury in a DCD model with prolonged warm ischemia.     

Amelioration of tumor necrosis factor release by cyclosporine in warm ischemia/reperfusion injury of the rat liver: with special reference to hepatic ultrastructure

Mechanisms by which an immunosuppressant (cyclosporine, CsA) ameliorates warm ischemic injury of the liver were studied. Female Sprague-Dawley rats were subjected to 60-min normothermic liver ischemia. Animals were assigned to one of two groups: group I, controls with vehicle treatment; group II, treatment with CsA (10 mg/kg). CsA was given orally for 4 consecutive days prior to the induction of hepatic ischemia. In addition to a survival study, plasma levels of endotoxin, serum activity of tumor necrosis factor-α (TNF), and serum levels of aminotransferases were measured in blood samples collected from the suprahepatic vena cava, and hepatic ultrastructural alterations were examined under an electron microscope. The 7-day survival rate was significantly higher in the CsA-treated animals. In the control group, serum TNF levels were elevated following reperfusion and peaked at 3 h. When the values at 3 h post reflow were compared, the animals given CsA had significantly lower levels of TNF (170.0 ± 30.5 pg/ml for group I, 67.6 ± 13.7 for group II, mean ± SEM; P < 0.05). The sinusoidal lining cells and hepatocytes were drastically destroyed at 6 h post reflow in the control group, although the degree of injury at 1–3 h was less severe. On the other hand, the endothelium and parenchymal liver cells in the CsA-treated group were well preserved at 6 h in comparison with those in the control group. Our data suggest that modulation of TNF production is one of the mechanisms through which CsA prevents the exacerbation of ischemia/reperfusion injury of the liver. Received for publication on Aug. 12, 1998; accepted on Feb. 2, 1999     

Failure of inosine to prevent ischemic damage in the canine and rat kidney models

Summary Intravenous, renal arterial, and intraperitoneal administration of inosine at dosages of 100 to 200 mg/kg, 160 mg/kg, and 200 mg/kg, respectively, in the dog and rat was used to test its efficacy in preventing ischemic damage after 60 min of warm ischemia in an in situ solitary renal model. No improvement of renal function as compared with a control and a conventional mannitol/furosemide treatment group was detected. Rather, inosine at dosages of160 mg/kg resulted in significantly impaired renal function in the experimental groups of the dog model; no improvement was observed in the rat model. These results suggest that the use of inosine in human renal surgery and preservation should be approached cautiously.     

Current status of kidney and pancreas transplantation in the United States, 1994–2003

This article reviews the OPTN/SRTR data collected on kidney and pancreas transplantation during 2003 in the context of trends over the past decade. Overall, the transplant community continued to struggle to meet the increasing demand for kidney and pancreas transplantation. The number of new wait-listed kidney registrants under the age of 50 has remained relatively stable since 1994, but the number of new registrants aged 50 to 64 has doubled. However, there was only a 2.3% increase in the total number of kidney transplants performed in 2003. Expanded criteria donor kidneys made up 20% of all recovered kidneys and 16% of all transplants performed, compared with 15% in the prior year. In May 2003, new rules were implemented to promote equity in kidney organ allocation. These changes seem to have improved access for historically disadvantaged groups, though they have reduced the quality of HLA matching. The effects on long-term outcomes have yet to be measured. Although the majority of SPK recipients are white (82%), the percentage of simultaneous kidney-pancreas recipients who are African-American has increased from 9% in 2000 to 16% in 2003. The percentage of Hispanic/Latino recipients increased from 5% to 9% over the same period.     

Inhibition of iNOS protects the aging heart against beta-adrenergic receptor stimulation-induced cardiac dysfunction and myocardial ischemic injury

BACKGROUND: beta-adrenergic receptor (AR) and aging are two major contributors to pathogenesis of perioperative myocardial ischemia and infarction. This study compared the response to beta-AR stimulation in the young and aging heart and examined the role of inducible nitric oxide synthase (iNOS) in aging related myocardial ischemic injury and its relation to beta-AR stimulation. MATERIAL AND METHODS: Isolated perfused hearts from young (3-5 months) and aging (24-25 months) rats were subjected to 60 min of 50% coronary flow reduction and 30 min of isoproterenol (Iso) stimulation starting at 30 min of ischemia. The rats were randomized to receive vehicle or 1400W (a selective iNOS inhibitor) at 24 h (2 mg/kg, i.p.) and 1 h (1 mg/kg, i.p.) pre-ischemia. RESULTS: The 30 min of myocardial ischemia resulted in cardiac dysfunction as indicated by a 13 to 45% of reduction in left ventricular developed pressure (LVDP) and +/- dp/dtmax in either young or aging rats. Infusion of Iso for 30 min caused a partial recovery of cardiac function in hearts from young animals receiving either vehicle or 1400W as evidenced by improvements in LVDP and +/- dp/dtmax. In striking contrast, Iso infusion to hearts from aging animals receiving vehicle not only failed to improve ischemia-induced cardiac depression but worsened cardiac function as indicated by a 43 to 60% further reduction in LVDP and +/- dp/dtmax at the end of 30-min Iso infusion, which was also associated with a significant increase in myocardial NO production, ONOO- formation, caspase-3 activation and creatine kinase (CK) release. However, the treatment with a selective iNOS inhibitor-1400W blocked NO production and ONOO- formation, attenuated caspase-3 activation and CK release, and improved LV function in the aging heart, demonstrating a critical link between iNOS generated NO production and aging myocardial ischemic injury. A significant increase of iNOS protein expression, activity and immunoreactivity was found in the baseline aging LV tissues versus their young counterparts. CONCLUSIONS: Aging induces phenotypic up-regulation of iNOS in the heart, in which beta-AR stimulation interacts with ischemia and triggers a markedly increased NO production, which creates a nitrative stress, generates toxic peroxynitrite, activates apoptosis, and eventually causes cardiac dysfunction and myocardial injury. An iNOS inhibitor-1400W can markedly attenuate these adverse effects in the aging heart.     

Immunodepressants ameliorate normothermic ischemia injury to the rat liver by down-regulating tumor necrosis factor, not by alleviation of lipid peroxidative injury

Abstract Mechanisms by which immunodepressants (Cyclosporine, CsA; FK 506, FK; Azanthioprine, AZA) ameliorate warm ischemic injury of the liver were examined. Female Sprague-Dawley rats were subjected to 60-min of normothermic liver ischemia. Animals were assigned to one of four groups: group I, control with vehicle treatment; groups II, III, and IV, treatment with CsA (10mg/kg), FK(1mg/kg), and AZA (1 mg/kg), respectively. The immunosuppressive agents were given per os for 4 consecutive days prior to the induction of hepatic ischemia. In addition to a survival study, plasma levels of endotoxin, serum activities of tumor necrosis factor-cc (TNF), plasma levels of phosphatidylcholine hydroperoxide (PCOOH) as a lipid peroxide, and serum alanine aminotransferase (ALT) were investigated in blood samples collected from the supra-hepatic vena cava. A 7-day survival period was significantly higher in the immunosuppressed animals. Serum TNF levels were elevated and peaked at 3 h following reper-fusion. When, the peak values were compared, the animals given immunodepressants had significantly lower levels of TNF (217.0 ± 40.6pg/ml for group I, 67.6 ± 13.7 for group II, 87.9±28.3 for group III and 89.1 519.9 for group IV; Mean k SEM). Plasma PCOOH levels were also elevated following reperfusion, but with no statistical difference among the groups. Our data suggest that immunodepressants ameliorate warm ischemia/reperfusion injury through modulation of TNF production and not through a diminution of lipid peroxidativp injury.     

The impact of ischemic lesions in the donor kidney,donor age,recipient age and HLA (A,B, C,DR, DQ) matching on clinical course after kidney grafting

It is generally accepted that HLA matching improves graft survival [1]. However, there is no consensus on whether this improvement is reflected on daily clinical course. Clinical course after renal transplantation depends on many factors, such as donor age, recipient age, ischemic score in the kidney [2], and HLA matching [3]. The relative contribution of these factors is unknown. Because management of the recipients in the various centers differs considerably, only a single centre study would reveal the relative contribution of all these factors. Therefore, in our centre we studied the influence of these parameters on the clinical course after renal allografting.