PATHOLOGICAL CHANGES IN SIX TREATED BABOON‐TO‐MAN RENAL HETEROTRANSPLANTS

Six baboon‐to‐man renal heterotransplants, each consisting of a pair of kidneys, were examined. Two had been removed from their recipients at forty‐nine and sixty days after transplantation because of the ever‐increasing doses of immunosuppressive drugs needed to control rejection; the other four pairs of kidneys were examined after death of the recipients at nineteen, twenty‐three, thirty‐five, and forty‐nine days. All the kidneys were enlarged. On the subcapsular surfaces of one pair there were petechias; four were mottled with irregular haemorrhages and infarcts; one pair had undergone almost complete hemorrhagic infarction. The transplants were heavily infiltrated with plasma cells, lymphocytes, large pyroninophilic lymphoid cells and eosinophils. Mitoses, “LE” cells and erythrophagocytosis were seen. Associated with this infiltration there was rupture of peritubular capillaries, interstitial cedema and widespread tubular damage. Fibrinoid necrosis of the walls of arterioles and interlobular arteries, with narrowing and obstruction of some vessels by fibrin and platelet deposits on the intima were common in all except one pair of kidneys. Associated with these vascular lesions there were focal infarcts and extensive interstitial haemorrhages. All the histological changes were more severe than those seen either in treated human renal homotransplants or in a comparable series of chimpanzee‐to‐man renal heterotransplants where cellular infiltration was slight and vascular lesions only present at the height of rejection. This work was aided by grants A‐6283, A‐6344, HE‐07735, AM‐07772, A1‐01452, and OG‐27 from the U.S. Public Health Service, and by a grant from the Medical Research Council. We would like to thank Drs D. Baitlon, J. Gordon, R. B. Hill, D. Lang, and D. E. Smith who performed the autopsies on these cases. We are particularly grateful to Dr D. T. Rowlands, who supervised most of the autopsies, for his helpful co‐operation throughout this study. Expert assistance in preparing the sections and photomicrographs was given by Miss Jane Rendall. © 1965 BJU International Compan

Future aspects of renal transplantation

New and exciting advances in renal transplantation are continuously being made, and the horizons for organ transplantation are bright and open. This article reviews only a few of the newer advances that will allow renal transplantation to become even more widespread and successful. The important and exciting implications for extrarenal organ transplantation are immediately evident. © 1988 Springer-Verlag

Bioenergetics Consequences of Mitochondrial Transplantation in Cardiomyocytes.

Background Mitochondrial transplantation has been recently explored for treatment of very ill cardiac patients. However, little is known about the intracellular consequences of mitochondrial transplantation. This study aims to assess the bioenergetics consequences of mitochondrial transplantation into normal cardiomyocytes in the short and long term. Methods and Results We first established the feasibility of autologous, non-autologous, and interspecies mitochondrial transplantation. Then we quantitated the bioenergetics consequences of non-autologous mitochondrial transplantation into cardiomyocytes up to 28 days using a Seahorse Extracellular Flux Analyzer. Compared with the control, we observed a statistically significant improvement in basal respiration and ATP production 2-day post-transplantation, accompanied by an increase in maximal respiration and spare respiratory capacity, although not statistically significantly. However, these initial improvements were short-lived and the bioenergetics advantages return to the baseline level in subsequent time points. Conclusions This study, for the first time, shows that transplantation of non-autologous mitochondria from healthy skeletal muscle cells into normal cardiomyocytes leads to short-term improvement of bioenergetics indicating "supercharged" state. However, over time these improved effects disappear, which suggests transplantation of mitochondria may have a potential application in settings where there is an acute stress

Second cadaver kidney transplants: Improved graft survival in secondary kidney transplants using cyclosporin A

A total of 42 patients who failed prior renal transplantation underwent repeat cadaveric transplantation cyclosporin A and low dose immunosuppression. Patient survival at 1 year was 100 per cent. Over-all graft survival was 83 per cent at 1 year, which was significantly better than had been obtained previously in this high risk group. Repeat cadaver transplantation with cyclosporin A is safe and offers those who have failed previous transplantation an opportunity for existence free of dialysis

Organ and tissue transplantation

A report is delivered on the First International Congress of the Transplantation Society (Paris 1967). The recent interest in transplantation of organs is largely due to the technical advances in surgical procedures making it possible to replace organs in the human, as well as to an increased understanding of the basic biological problems underlying the rejection of such grafts. At this first International Congress, widely ranging topics were discussed, including organ transplantation, mechanism of graft rejection, methods of immunosuppression, genetics of transplantation, bone marrow transplantation, and cancer as homograft. New techniques of organ transplantation, new concepts in the antigenic structure of cells, new methods of purifying subcellular fraction of antilymphocytic serum, new drugs to combat rejection phenomena, and above all a fresh outlook on the mode of action of these drugs at a molecular level, will doubtless render this an exciting new approach to biology in general and to clinical problems in particular.peer-reviewe

Changing perspectives on liver transplantation in 1988.

After liver transplantation for cancer, there is a high incidence of disease recurrence within 18 to 36 months for most tumors, although there are a small number of long-term survivors. An extended resection of the upper abdominal viscera with replacement by a liver-pancreas cluster is being tried in Pittsburgh for lesions which have not been successfully managed with liver transplantation alone. Despite a high incidence of graft reinfection after liver transplantation for hepatitis B virus (HBV) related disease, a significant proportion of patients achieve long-term survival. Hyperimmune globulin and interferon have been of little benefit in preventing reinfection. Clinical trials with a human monoclonal antibody to HBsAg are in progress. Transplantation for alcoholic liver disease has been considered controversial. However, survival after liver transplantation for Laennec's cirrhosis is comparable to survival after liver transplantation for other chronic, benign, and non-HBV related liver diseases. Sclerotherapy followed by liver transplantation is the treatment of choice for patients with acute hemorrhage from esophageal varices and end-stage liver disease. Sclerotherapy alone or followed by selective shunting is an appropriate alternative in patients with good hepatic reserve. Only 25% of infants with biliary atresia benefit from portoenterostomy. To meet the demand for small infants waiting for transplantation, several transplant programs have successfully expanded their efforts to use partial (reduced) liver grafts. Cyclosporine and low-dose prednisone remain the basis for immunosuppression after liver transplantation. However, nephrotoxicity and hypertension are frequent and troublesome side effects of cyclosporine. Triple and quadruple drug regimens have been increasingly popular in an effort to minimize cyclosporine toxicity. Phase 1 clinical trials with a new drug, FK506, recently began in Pittsburgh. Hyperacute rejection of the liver has been demonstrated in animal models and has been strongly suspected in recent clinical descriptions of acute hemorrhagic necrosis after liver transplantation. So far, only transplantation across an ABO incompatibility has been identified as a risk factor for hyperacute rejection. The new preservation solution developed by Belzer and associates at the University of Wisconsin has significantly extended the preservation time for liver grafts, and improved the quality of liver preservation

Diabetic microangiopathy in Type 1 (insulin-dependent) diabetic patients after successful pancreatic and kidney or solitary kidney transplantation

To evaluate the beneficial effect of pancreatic grafting on peripheral microcirculation and long-term clinical outcome, we compared data of 28 Type 1 (insulin-dependent) diabetic patients either given a pancreatic and kidney graft simultaneously or given a solitary kidney graft (n=17). Peripheral microcirculation was estimated by transcutaneous oxygen pressure measurement (including reoxygenation potential after blood flow occlusion) and erythrocyte flow / velocity by a non-contact laser speckle method. All the measured parameters showed significant differences between diabetic and control subjects in the mean follow-up time of 49 (simultaneous pancreas and kidney transplantation) and 43 (solitary kidney transplantation) months. The data from patients after simultaneous pancreas and kidney transplantation revealed an improvement of transcutaneous oxygen pressure measurement (rise from 46±2 mm Hg to 63±3 mmHg), reoxygenation time (fall from 224±12s to 114±6s) and laser speckle measurement (rise from 4.2±1.7 to 5.6±1.8 relative units). The control group with solitary kidney transplantation did not show a positive evaluation. Data from patients after simultaneous pancreas and kidney transplantation revealed an improvement in transcutaneous oxygen pressure measurement, reoxygenation time and laser speckle measurement whereas the control group with solitary kidney transplantation did not show a positive evaluation. Improved microcirculation was more pronounced in patients with better microvascular preconditions. The results confirm that diabetic microangiopathy is positively influenced by pancreatic transplantation

Sociodemographic factors and patient perceptions are associated with attitudes to kidney transplantation among haemodialysis patients

Background. Treatment decisions made by patients with chronic kidney disease are crucial in the renal transplantation process. These decisions are influenced, amongst other factors, by attitudes towards different treatment options, which are modulated by knowledge and perceptions about the disease and its treatment and many other subjective factors. Here we study the attitude of dialysis patients to renal transplantation and the association of sociodemographic characteristics, patient perceptions and experiences with this attitude. Methods. In a cross-sectional study, all patients from eight dialysis units in Budapest, Hungary, who were on haemodialysis for at least 3 months were approached to complete a self-administered questionnaire. Data collected from 459 patients younger than 70 years were analysed in this manuscript. Results. Mean age of the study population was 53 +/- 12 years, 54% were male and the prevalence of diabetes was 22%. Patients with positive attitude to renal transplantation were younger (51 +/- 11 versus 58 +/- 11 years), better educated, more likely to be employed (11% versus 4%) and had prior transplantation (15% versus 7%)(P < 0.05 for all). In a multivariate model, negative patient perceptions about transplantation, negative expectations about health outcomes after transplantation and the presence of fears about the transplant surgery were associated, in addition to incre- asing age, with unwillingness to consider transplantation. Conclusions. Negative attitudes to renal transplantation are associated with potentially modifiable factors. Based on this we suggest that it would be necessary to develop standardized, comprehensible patient information systems and personalized decision support to facilitate modality selection and to enable patients to make fully informed treatment decisions

Thoracic duct drainage in organ transplantation: Will it permit better immunosuppression?

It is possible that thoracic-duct drainage, a major but neglected immunosuppressive adjunct, can have an important impact on organ transplantation. If thoracic-duct drainage is started at the time of transplantation, the practicality of its use in cadaveric cases is greatly enhanced. With kidney transplantation, the penalty of not having pretreatment for the first organ is compensanted by the automatic presence of pretreatment if rejection is not controlled and retransplantation becomes necessary. The advantage of adding thoracic-duct drainage to conventional immunosuppression may greatly enhance the expectations for the transplantation of extrarenal organs, such as the liver, pancreas, heart, and lung. There is evidence that pretreatment with thoracic-duct drainage of patients with cytotoxic antibodies may permit successful renal transplantation under these otherwise essentially hopeless conditions. Exploration of the neglected but potentially valuable tool of thoracic-duct drainage seems to the authors to be highly justified in other centers

Evaluation of protocol before transplantation and after reperfusion biopsies from human orthotopic liver allografts: Considerations of preservation and early immunological injury

Light microscopic, immunohistochemical and ultrastructural analysis of protocol before transplantation and after reperfusion biopsy specimens from 87 randomly selected patients was performed to assess the contribution of preservation and immunological injury to early graft failure. Most biopsy specimens were essentially normal by light microscopy before transplantatio, and no particular feature could be relied on to predict function after transplantation. Ultrastructural examination of biopsy specimens before transplantation demonstrated preferential degeneration of sinusoidal lining cells, but no strict correlation was seen between ultrastructural sinusoidal integrity before transplantation and function after transplantation. The presence of zonal or severe focal necrosis and a severe neutrophilic exudate in biopsy specimens after reperfusion presaged a poor early postoperative course in most, but not all, patients. The presence of preformed lymphocytotoxic antibodies had no effect on the early clinical course, but was associated with Kupffer cell hypertrophy in needle biopsy specimens taken after transplantation. No definite evidence was seen of hyperacute rejection as a result of preformed lymphocytotoxic antibodies as detected in conventional assays. These findings suggest that preservation injury accounts for only a subset of grafts that fail to function after transplantation. Other perioperative or “recipient” factors may be of equal or greater importance in early graft dysfunction or failure.(HEPATOLOGY 1990;11:932‐941.). Copyright © 1990 American Association for the Study of Liver Disease