Selected activities in Scandiatransplant.

Scandiatransplant is the Nordic organ exchange organization. It has existed for 35 years and it is owned by all organ transplantation hospital departments in the five Nordic countries--Denmark, Finland, Iceland, Norway, and Sweden. The use of living organ donors for kidney transplantation has become a more common procedure not only in Norway but also in Sweden and Denmark. For the first time, in 2003, one transplant center performed relatively more living donor kidney transplantations than with deceased donors. The overall organ transplant activity reveals a remarkably stable situation in the area covered by Scandiatransplant. Scandiatransplant as an organ exchange organization has changed from a solely kidney exchange organization to an organization in which the more immediate vital organs as liver and heart are exchanged more commonly than kidneys.

Superoxide dismutase as an inhibitor of postischemic microvascular permeability increase in the hamster.

The purpose was to elucidate the involvement of superoxide radical (O2-.) in the postischemic increase in the vascular permeability in the hamster cheek pouch. Cheek pouches of anesthetized hamsters were everted, prepared for intravital microscopy, and superfused with a bicarbonate buffered saline solution. Local ischemia for 30 min was obtained using a cuff placed around the proximal part of the cheek pouch. The vascular permeability in the postcapillary venules was quantified as leakage of intravenously injected fluorescein labeled dextran (FITC-dextran, Mw 150,000), using intravital microscopy and fluorimetry. There was a significant and reversible permeability increase after the reperfusion started. In the first series of experiments, combined intravenous infusion and topical application of human recombinant extracellular superoxide dismutase C (EC-SOD C) reduced the postischemic permeability response by 80%. Bovine CuZn-SOD given in exactly the same way reduced the response by 60%. In the second series of experiments, inactivated EC-SOD C was given to the control animals and active EC-SOD C was given to the treated animals. The topical treatment was excluded. Only active EC-SOD C reduced significantly the postischemic permeability increase when present during the ischemic period. Treatment with mannitol (i.v.) did not alter the postischemic response. Since active EC-SOD C and CuZn-SOD but not inactivated EC-SOD C effectively inhibited the response, we suggest that the superoxide anion is involved in the mediation of the postischemic permeability increase in the hamster.

Ischemic heart disease--major cause of death and graft loss after renal transplantation in Scandinavia.

Causes of graft loss and death were studied in 1347 recipients of primary renal transplants followed for 5 years after transplantation irrespective of graft function. Immunosuppression consisted of high or medium dose CsA and prednisolone or low dose CsA and prednisolone and azathioprine. In recipients of cadaver grafts, death with a functioning transplant was more common than graft rejection after the first posttransplant year, accounting for 49% and 41% of the graft losses, respectively. Of deaths with a functioning graft, 53% were due to ischemic heart disease (IHD) and 10% were due to other vascular disease. In the 55- to 64-year-old age group, the risk of death from IHD was 6.4 times higher in the transplanted nondiabetic patients, 8.6 times higher in the dialysis patients (European Dialysis and Transplant Association figures), and 20.8 times higher in the transplanted diabetic patients than in the general population (national figures). A multivariate Cox regression analysis showed that old age, diabetes mellitus, occurrence of acute rejection, pretransplant transfusions, delayed onset of graft function, and male gender were significant for death in IHD. We conclude that, in comparison to reports from other regions, Scandinavian renal transplant recipients are at high risk of dying of IHD. Future advances in long-term renal graft survival will depend largely on the success of preventing myocardial infarction and death in this patient population.

The impact of acute rejection episodes on long-term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens.

To characterize factors of importance for the occurrence of acute rejection as well as study the impact of these episodes on long-term renal survival and function, a total of 819 acute rejection episodes were studied in 951 primary cadaveric donor kidney recipients (CD) and in 396 primary living donor kidney recipients (LD). The patients were treated by three immunosuppressive schedules, namely, CsA given in a high dose, a medium dose, or a low dose. Additionally, all patients received PRED and patients in the low-dose group received AZA. The incidence of acute rejection was higher and occurred earlier after transplantation in the CsA medium dose and low dose groups than in the CsA high dose group (P < 0.05 and P < 0.01, respectively). Although the incidence of first acute rejection was similar in CD and LD patients, 59.1% vs. 60.6%, it was successfully reversed by antirejection treatment in a higher percentage in LD patients. The estimated graft half-life was shorter in patients who had acute rejection episodes than those who did not, 6.6 years vs. 12.5 years in CD patients (P < 0.0001). Renal function at 1-5 years after transplantation was stable, but significantly poorer in CD patients who had experienced acute rejection than in patients who had not, with the mean creatinine clearance rates in the ranges 45-47 vs. 54-60 ml/min in the other groups (P < 0.0001). In a stepwise Cox regression analysis in CD recipients, risk factors for acute rejection were CsA (low dose) treatment schedule, immunization as displayed by presence of panel-reactive antibodies and positive B cell cross-match, young recipient age, disease of diabetes mellitus, and HLA-DR mismatching. In LD recipients, the corresponding risk factors were treatment schedule, young recipient, HLA mismatching, and transplantation from parent to child. Thus, the study has demonstrated some factors of importance for acute rejection episodes in CsA-treated patients as well as showing the detrimental effect of these episodes on long-term graft survival and renal function. These results suggest that a primary aim of future treatment strategies should be to reduce the incidence of these episodes.

Hepatitis C superinfection in hepatitis C virus (HCV)-infected patients transplanted with an HCV-infected kidney.

Hepatitis C virus (HCV) genotypes, determined by polymerase chain reaction with type-specific primers, were studied in 5 already HCV-infected patients receiving kidneys from HCV-infected cadaver donors. Three patients were investigated retrospectively using stored pre- and posttransplantation sera and followed 18-28 months after transplantation. Two recipients with HCV genotype 2b infection had received kidneys from 1 genotype 3a-infected donor. In 1 recipient, HCV 2b was replaced by the donor's type; in the other recipient, a prolonged mixed infection of 3a and 2b occurred. Persistent alanine aminotransferase (ALT) elevation (3- to 5-fold) appeared in both patients. The third patient, also HCV 2b infected when transplanted with an HCV 3a-infected kidney, remained infected with HCV 2b only. Two patients, one with HCV genotype 1b and the other with genotype 3a, were followed prospectively with frequent bleeds (initially biweekly) and genotyping over 14 months after they had received kidneys from 1 HCV genotype 1a-infected donor. The HCV 1b-infected recipient remained infected with 1b only and had minimal biochemical signs of liver injury. In the other recipient, mixed infection of 3a and 1a appeared at week 3 and persisted for several weeks, until only genotype 1a could be detected. This patient had elevated ALT levels before transplantation. After onset of mixed infection, ALT levels increased further for several weeks, and returned to pretransplantation levels when only HCV 1a was found. HCV-infected kidneys transplanted into HCV-infected recipients gave 3 different virus patterns. Most patients benefitted in the short term, but some super-infected patients experienced increased liver damage.

A randomized trial of cyclosporine and prednisolone versus cyclosporine, azathioprine, and prednisolone in primary cadaveric renal transplantation.

A randomized trial was performed with the aim to compare two immunosuppressive treatment schedules in adult recipients of first cadaveric renal transplants. A total of 229 patients were randomized to double therapy with cyclosporine and prednisolone and 234 patients were randomized to triple therapy with cyclosporine, azathioprine, and prednisolone. Minimum follow-up was 4 years. The actuarial 5-year patient survival was 79.8% in the double therapy group and 82.3% in the triple therapy group (n.s.). The corresponding graft survival figures were 54.4% and 59.6% in the two groups, respectively (n.s.). There were no differences between the groups regarding cause of death or cause of graft loss. Renal function as determined by serum creatinine did not differ between the groups and was stable throughout the observation period. Azathioprine was instituted in a total of 51 patients randomized to double therapy. This subgroup of patients had a patient and graft survival not different from the remaining patients randomized to double therapy or from the patients randomized to triple therapy. There were no differences between the double and triple therapy groups regarding incidence and timing of acute rejection or infections. The incidence of other medical diseases and adverse events such as nephrotoxicity or malignancy did not differ between the groups. Azathioprine-induced leukopenia was uncommon (19 episodes in the triple therapy group). In a multivariate analysis of the whole series the only covariates that significantly influenced graft survival were age of recipient and occurrence of acute rejection, while among other factors treatment schedule did not. Thus this prospective study, in accordance with previous such studies, failed to find support for the use of triple therapy as first choice immunosuppression in first cadaveric renal transplantation. However, the study could not rule out the possibility that some patients at risk for the development of irreversible rejection or nephrotoxicity of CsA might benefit from the addition of azathioprine to the treatment schedule.

Longstanding groin pain in athletes. A multidisciplinary approach.

In 21 male athletes (age 20 to 40 years) with longstanding unexplained groin pain, a multidisciplinary investigation was performed in order to reveal the underlying cause. These examinations included general surgery for detection of inguinal hernia and neuralgia, orthopaedic surgery for detection of adductor tenoperiostitis and symphysitis, urology for detection of prostatitis, radiology for performing herniography and plain film of the pelvic bones, nuclear medicine for isotope studies of the pubic bone and symphysis. In 19 patients there was a positive diagnosis for 2 or more of the diseases (10 patients had 2 diseases, 6 patients had 3 diseases, 3 patients had 4 diseases). Two patients had only signs of symphysitis. Our results show the complexity of longstanding groin pain in athletes. It also explains why therapy for one specific disease entity may fail. We conclude that this clinical setting demands the recruitment of a team with experience of different aspects of groin pain.

Scandiatransplant: organ transplantation in the Nordic countries 1996.

The Nordic collaboration in organ transplantation was initiated nearly 30 years ago in the frame of Scandiatransplant. With a recent formalization of its structure, Scandiatransplant has become a modern organ exchange organization. The increasing activities of Scandiatransplant clearly reflect the continuously growing need for a close and firm Nordic collaboration in the transplantation field, for the benefit of the numerous patients waiting for an organ transplant.

Heparinization of polytetrafluoroethylene (ePTFE) grafts. The effect on pseudointimal hyperplasia.

A study was undertaken to evaluate the effect of a covalent heparinization on thrombogenicity of ePTFE grafts in sheep. With scanning electron microscopy heparinization occurred as a thin smooth layer covering the network of ePTFE. Most of it had disappeared already after 2 hours. In long-term experiments a high and low flow part of the ePTFE graft was created in the carotid artery system. The heparinization had no effect on patency and there was no difference between the high and low flow parts of the graft. The graft surface was covered with fibrous tissue, which was significantly thicker than the pannus in the host vessel. In the graft interstices (internodal distance of 30 micron) capillaries were seen without difference between occluded and patent grafts. The capillary density was significantly higher proximally than distally.

Edema after lower limb arterial reconstruction. Influence of background factors, surgical technique and potentially prophylactic methods.

The pathogenesis of lower leg edema regularly following a distal arterial reconstruction is unclear and generally no treatment is used. In 85 patients background factors such as diabetes, age, sex and side of operation were analysed and found not to influence the degree of edema. A significantly less pronounced edema was found when a prosthetic graft was used as compared to a vein graft as well as if the distal anastomosis was located above as compared to below the knee. Both these findings might be explained by differences in incisions. In a pilot series the prophylactic effect of various pharmacological regimens was studied and in another 22 patients leg elevation was prescribed. None of the drugs (furosemide, mannitol, terbutaline and corticosteroids) appeared to prevent the development of edema. Within the leg elevation group there was, like in patients without special treatment, less swelling if the distal anastomosis was performed above the knee and if a prosthetic graft was used. In these cases leg elevation seemed to prevent swelling with significantly less edema than corresponding patients treated without leg elevation.

Procedures and criteria for accepting the renal patient for inclusion on the waiting list for kidney transplantation in the Nordic countries.

BACKGROUND: The overall aim of this study was to survey and analyze the selection process for patients awaiting a kidney in the Nordic countries collaborating within Scandiatransplant. METHODS: A two-parts questionnaire was sent to one senior physician at each of the 10 Scandiatransplant kidney transplantation centers that use deceased donors. The first part consisted of questions related to the evaluation of a patient for the waiting list. The second part of the questionnaire dealt with 12 borderline cases, based on experiences at seven of all centers. Answers should be given with the policy of the center in mind. The response rate was 100%. RESULTS: Some centers are stricter than others regarding limits for body mass index and cardiac ejection fraction. At three centers, human immunodeficiency virus-positive patients are not included on the list. Four centers have a policy of not including predialysis patients. All centers agreed that they would not refrain from acceptance of a patient due to the scarcity of organs, if the patient was considered to benefit medically from transplantation. Reevaluation of the patient once on the list is done at all centers, focusing on cardiovascular problems. Only a few respondents were positive to the idea of common Nordic guidelines for investigations or for limiting values. CONCLUSIONS: We concluded that there are some, mainly small, differences among Nordic countries regarding procedures and criteria for acceptance of patients on the waiting list for kidney transplantation. The interest in common guidelines is limited.