Lundgren G

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 HID. Future advances in long-term renal graft survival will depend largely on the success of preventing myocardial infarction and death in this patient population.

Drug metabolism in human liver in vitro: Establishment of a human liver bank

Marked species differences in xenobiotics metabolism in the liver seriously limit extrapolations from animals to man. Because access to human liver is limited and periodic, we have set up a human “liver bank” available for metabolic studies. The liver tissue is obtained shortly after circulatory arrest from cadaveric (cerebral infarction) kidney transplant donors. Postmortem changes are minimal. Subcellular liver fractions are prepared immediately and part of this is used directly for assay. Intact pieces and subcellular fractions are stored in different media at −80°. Each liver is characterized by light and electron microscopy. Several enzymes, including cytochromes P‐450 and b5, NADPH‐cytochrome c reductase, demethylation of aminopyrine and amitriptyline, epoxidation of carbamazepine, oxidation of acetaminophen, and benzo[a]pyrene, were tested with freshly prepared fractions so that each liver got a “drug metabolic profile.” This “test battery” was repeated after storing to evaluate the effect of storage. Our preparation technique gave a well‐preserved microsomal fraction with minimal contamination. In freshly prepared microsomes the following activities (levels) were observed: cytochrome P‐450, 0.13 to 0.73 nmole/mg protein; NADPH‐cytochrome c reductase, 70 to 426 nmole/mg protein; demethylation of aminopyrine, 0.9 to 4.1, and of amitriptyline, 0.11 to 0.92 nmole/mg protein; carbamazepine‐10,11 epoxidation, 0.03 to 0.46 nmole/mg protein; oxidation of acetaminophen, 0.48 to 2.11, and of benzo[a]pyrene, 0.04 to 0.11 nmole/mg protein · min. These values are generally higher than in the literature. Our storage conditions were efficient: most of the activities were well preserved during storage for at least 6 mo. When pairs of enzyme activities (levels) were plotted against each other with fresh tissue there was good correlation between some but not all activities.

CYTOMEGALOVIRUS INFECTION ASSOCIATED WITH AND PRECEDING CHRONIC GRAFT-VERSUS-HOST DISEASE

Of 68 consecutive allogeneic bone marrow transplant patients, 53 survived more than three months after transplantation. Twenty-two (42%) developed chronic graft-versus-host disease (GVHD). Chronic GVHD was more common among patients who had previously experienced cytomegalovirus (CMV) infection (20/36, 56%) than among those without signs of active CMV infection (2/17, 12%) (P<0.01). The CMV infections preceded the development of chronic GVHD by a median of 128 days (range 23–322 days). Children below 14 years of age who had had CMV infection developed chronic GVHD as often as older patients (8/14 vs. 12/22). CMV infection may pave the way for chronic GVHD.

SUCCESSFUL OUTCOME OF SEGMENTAL HUMAN PANCREATIC TRANSPLANTATION WITH ENTERIC EXOCRINE DIVERSION AFTER MODIFICATIONS IN TECHNIQUE

Segmental pancreatic transplantation is now the most widely favoured form of pancreatic transplantation, but the major difficulty with this procedure is the handling of the exocrine secretion. The use of a pancreaticoenteric anastomosis for exocrine diversion has been re-evaluated and several ancillary measures to reduce the risk of fistula and bacterial contamination have been applied. In three consecutive patients there have been no complications related to the exocrine pancreas. The pancreatic and renal grafts of these patients are functioning well 7, 3, and 2 months, respectively, after transplantation.

HLA-MATCHING AND PRETRANSPLANT BLOOD TRANSFUSIONS IN CADAVERIC RENAL TRANSPLANTATION—A CHANGING PICTURE WITH CYCLOSPORIN

613 patients were included in a study to assess the extent to which HLA-matching and pretransplant blood transfusions affect the outcome of cadaveric renal transplantation in patients treated with cyclosporin and low doses of prednisolone. Matching for the HLA-DR-antigens significantly reduced the frequency of rejection episodes, but neither HLA-matching nor pretransplant blood transfusions influenced the patient and graft survival rates.

Experience with a cooperative bone marrow transplantation program in Stockholm

Twenty-seven patients (age range from 1 to 55 years) were included in a cooperative bone marrow transplantation program in Stockholm. Of eight patients with severe aplastic anemia (SAA), two died following graft rejection and six (75%) are alive between 3 months and 4½ years after transplantation. Two patients with end stage leukemia died of septicemia and bleeding shortly after transplantation. Thirteen of 17 patients (76%) with acute leukemia in their first or second remission are alive 1 to 16 months after transplantation. Death was caused by septicemia in two patients, interstitial Candida pneumonitis in one and gastrointestinal bleeding in association with graft-versus-host disease in one. Among the leukemic patients all deaths occurred in subjects over 17 years of age and all 10 children are alive. No relapse has yet been seen. Successful bone marrow transplantations were carried out utilizing ordinary hospital resources only. This justifies the practice of performing transplantations in subjects with SAA and acute leukemia in remission even outside specially equipped and designed bone marrow transplantation units.

CADAVERIC RENAL TRANSPLANTATION IN PATIENTS OF 60 YEARS AND ABOVE

Between 1971 and 1977, 34 patients aged 60 years and above were treated with cadaveric renal transplantation in Stockholm. The survival figures were nearly the same as for patients of the same age group that had undergone long-term dialysis, with 2-year survival rates of 49 and 45%, respectively. Comparison with a younger group of transplant patients, ages 16 to 49, showed poorer patient and graft survival figures for the older patients, with 49 and 38%, respectively, after 2 years against 70 and 56% for the younger group. Complications were more frequent among the older patients, especially in regard to serious infections, heart conditions, and steroid diabetes. Irreversible rejection, on the other hand, was less common in the older group. On the basis of these findings, we intend continuing to offer renal transplantation to patients of 60 years and above. It would, moreover, seem worthwhile to try to reduce the dose of prednisolone in these patients.

Living related kidney donors: complications and long-term renal function.

SUMMARY Sixty-two living related kidney donors were nephrectomized ring a 10-year period. The overall complication rate was, most complications being minor. Among the major nplications was one patient with pulmonary embolism and see patients with hepatitis. One female donor suffered a choneurotic reaction following rejection of the donated lney and she is still away from work, more than 2 years yaer. The other 61 donors were back to work within 2 to 18 ean 8) weeks. The mean serum creatinine levels increased μm 0.95 preoperatively to 1.15 mg/100 ml at the followup mination, which took place between 6 months and 9 years yaer nephrectomy. The mean increase in serum creatinine is higher in donors above 50 years of age (P< 0.02). The an creatinine clearance of the whole group decreased from to 90 ml/min. The mean increase in size of the remaining lney was 22%. Donor nephrectomy is a safe procedure with serious complications and the prognosis for the recipient excellent. Therefore, we consider transplantation from a nily member to be the treatment of choice in terminal mia.

DRAINAGE OF THORACIC DUCT LYMPH IN RENAL TRANSPLANT PATIENTS

SUMMARY Lymphocyte depletion by drainage of lymph via a thoracic duct fistula was accomplished in 51 renal transplant recipients as an adjunct method for immunosuppression. The duration of lymph flow varied between 2 and 53 days and the total drained lymph volume between 1 and 168 liters. The graft survival of these patients was compared to that of a control group of patients undergoing transplantation during a similar period. The followup period was 2–6 years. In patients receiving transplants from living related donors, no beneficial effect of lymphocyte depletion was demonstrated, probably because of the satisfactory graft survival among the control patients (84% at 1 year). However, in recipients of cadaveric kidneys, a significantly higher 1-year graft survival was achieved in the lymph-drained patients. Drainage for more than 30 days and of more than 20 liters improved the results. Additional suppression by thymectomy and institution of antilymphocyte globulin suggested that the best treatment would be a combination of both these measures with lymph drainage continuing for more than 30 days. Infection around the thoracic duct cannula occurred in 5 patients, necessitating removal of the cannula in 2. Two patients developed septicemia. In one of them the infection originated from an infected incisional wound and in the other probably from reinfusion of contaminated lymph plasma. Two other patients developed malignant tumors 23 and 58 months after transplantation, respectively. It is felt that lymphocyte depletion by lymph drainage is an effective supplementary method of immunosuppression to enhance graft survival in recipients of cadaveric renal transplants.

Improved results in pancreatic transplantation by avoidance of nonimmunological graft failures

Twenty eight consecutive combined renal and pancreatic transplantations with enteric exocrine diversion were performed between June 1984 and May 1986. The one-year actuarial patient survival and renal and pancreatic graft survival were 90%, 67%, and 69%, respectively. Nineteen pancreatic grafts and eighteen renal grafts are currently functioning at 1–24 months. Of the pancreatic graft losses only 2 were attributable to non-immunological complications. No pancreatic graft was lost due to pancreaticoenteric leakage or vascular thrombosis. This was achieved by reducing the cold ischemia time and by adopting an aggressive anticoagulant policy. In all patients with functioning grafts the fasting blood glucose, glycosylated hemoglobin level, and oral glucose tolerance test were normal. The intravenous glucose tolerance test was normal in most of the patients but subnormal in some.