Measures to decrease HLA antibodies in immunized patients awaiting kidney transplantation.
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Biomedical subjects
Publications and source records attributed to H Brynger.
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In countries which reported to the registry of the European Dialysis and Transplant Association (EDTA)-European Renal Association, 2.4% of 147 092 treated patients were recognized as having analgesic nephropathy (AN) as the cause of end-stage renal failure (ESRF) on 31 December 1986. A small number of patients had other specific drug nephropathies, but these do not yet make an important contribution to ESRF treatment programmes. It is possible that more patients have ESRF due to AN, and evidence from studies of age distribution, the demography of urothelial malignancies, a special study of diagnostic criteria, data on sales of analgesics, and a study of regional areas of high incidence lend some support to that view. Changes in prescription and self-medication practices over the last 20 years have almost eradicated analgesic nephropathy from the U.K. and Sweden, two countries in which there was previously a high frequency of ESRF due to AN. In other countries where action has been taken more recently, cases are still reported fairly frequently, and this seems likely to continue for several years to come.
This paper summarises the information given on the 1986 EDTA Registry centre questionnaire which was returned by 82% of the 2,065 known dialysis and transplant centres in 33 European countries. Information is given on the number of patients alive on haemodialysis according to the type of dialysis facilities available where the patient was receiving dialysis and the number of patients receiving special types of dialysis. The centre questionnaire also included questions on testing for HIV infection, serological evidence or symptoms of AIDS and the diagnosis of hepatitis B in patients and staff. The data given in response to these questions are presented together with data on the involvement of dietitians and social workers in the treatment of patients with end stage renal failure. Finally, information on transplant activity in Europe and the treatment policies of transplanting centres is provided.
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Diabetic nephropathy, a rarely listed cause of end-stage renal failure (ESRF) among patients starting renal replacement therapy (RRT) in the early seventies, has progressively gained in importance and become one of the major reasons for the continuous growth of the patient population on RRT in most European countries. Amongst new patients commencing RRT in 1985, the acceptance rate varied between 3 and 12 per million population for type I diabetes mellitus and between one and four per million population for type II diabetes mellitus. Nordic countries, particularly Sweden and Finland, had the highest acceptance rate of young patients with type I diabetes mellitus whose median ages were 38-42 years. In most central and southern European countries the median age of patients with type I diabetes mellitus varied between 50 and 58 years. The high number of young patients with type I diabetes mellitus and ESRF in Nordic countries point to a different natural history of this disease. It cannot be excluded, however, that the higher median age in other countries might result from doctors mistakenly diagnosing type I disease in patients with type II disease who need insulin treatment. Patients with type II diabetes mellitus had a similar age distribution at start of RRT throughout Europe and their median ages clustered around 60 years in most countries. The contribution of haemodialysis, peritoneal dialysis and renal transplantation was analysed for diabetic compared to non-diabetic ESRF. Despite large geographical differences in the proportional use of methods of treatment, a general trend to apply CAPD more frequently in diabetic as compared to non-diabetic patients was observed, and this was true for countries with both predominant haemodialysis and predominant transplant programmes. Transplantation without prior dialysis was performed in 17% of Swedish and 30% of Norwegian patients with type I diabetes mellitus. In order to better explain the mortality of patients with diabetic ESRF, the proportional distribution of causes of death was analysed. Myocardial ischaemia and infarction was confirmed to be the leading cause of death in patients with diabetes mellitus on RRT. The coronary death rate was estimated to be 10 times greater in young patients with type I diabetes mellitus as compared to their non-diabetic counterparts. Other cardiovascular as well as infectious causes were recorded in a similar proportion of deaths in diabetics as in non-diabetics. Cancer deaths, however, appeared to be definitely less frequent in patients on RRT due to diabetic nephropathy.
This study was designed to investigate the influence of systemic immunosuppressive therapy on the HLA-DR expression of epidermal Langerhans cells. Fifteen renal allograft recipients immunosuppressed with cyclosporin A and steroids were studied. Skin biopsies were taken from the upper arm prior to transplantation and at different intervals during the post-transplantation period. The epidermis was separated from the dermis, and the epidermal sheet was subjected to immunohistochemistry in order to make the HLA-DR antigens on the Langerhans cells visible. Following 2 days of immunosuppression, the number of Langerhans cells expressing HLA-DR antigens started to decrease and after 1 week, only 60% of the initial number of positive cells were detected. The number of positive cells remained low throughout the experimental period. It is suggested that systemic immunosuppressive therapy will suppress the expression of HLA-DR antigens on epidermal Langerhans cells, something which may mirror a systemic effect on other antigen-presenting cells.
Transplantation tolerance was induced in 50% of Wky rats treated with antithymocyte globulin (ATG) 2 days prior to transplantation of a PVG/c heart. The induction period immediately following ATG treatment and transplantation was characterized by instability, with 50% of the allografts being lost in rejection within 30 days after transplantation. Second syngeneic transplantation to ATG-treated recipients 5 days after the first transplantation facilitated tolerance induction and permanent acceptance of both transplants. Thirty days after ATG treatment and the primary transplantation, 50% of second syngeneic allografts were accepted. During the early period after transplantation a continuous antigen presence together with ATG was necessary. Graft removal and absence of the transplant for 3 days, close to ATG administration, resulted in rejection of a second PVG/c transplant. Furthermore, the induction phase could easily be manipulated by the addition of sensitized or tolerized spleen cells to the recipient, causing allograft rejection or tolerance, respectively. Sixty days after ATG treatment and transplantation, a longer period between graft removal and retransplantation was required to break tolerance. Injection of sensitized spleen cells at this time did not affect graft survival, indicating an increased stability of the unresponsive state 60 days after ATG treatment and transplantation.
Extensive survival data are presented from the EDTA Registry's files for patients who started renal replacement therapy in 1970-1974 compared to 1980-1984. The contribution of the different treatment modalities (haemodialysis, continuous peritoneal dialysis, and transplantation) to the survival of patients according to geographical region is also shown. Survival on renal replacement therapy, irrespective of treatment modality and of primary renal disease, was best in the 10-14-year-old patients, with 58% at 10 years and 52% at 15 years, and decreased with rising age to 28% at 10 years and 16% at 15 years in patients aged 45-54 when they commenced therapy in 1970-1974. When comparing the 0-4-year-old with the 10-14-year-old cohort of the paediatric patients, 5-year survival rates for patients starting renal replacement therapy in the early eighties declined from 85% to 70% with decreasing age. Treatment policy, as reflected by the proportion of patients on different modes of therapy, varied markedly between European regions but affected survival to a small extent only. The large population with diabetic nephropathy incurred annual mortality rates 2-3 times greater than those observed in patients with 'standard' primary renal diseases. Haemodialysis and continuous peritoneal dialysis, although not comparable because of important differences in selection policy, yielded similar survival rates. Patients and graft survival rates have improved markedly when comparing patients starting renal replacement therapy in the early seventies with the eighties; particularly for cadaveric transplantation. Patient survival after second grafting was similar to that after first grafting, with 83% at 5 years after second cadaveric grafting in the 15-44-year-old cohort, vs 85% after first cadaver transplantation in 1980-1984. Second cadaveric graft survival was superior to average first-graft survival for those recipients whose first graft had been functioning for more than 1 year. However, second-graft survival in rapid rejectors of a first graft as well as third cadaveric graft survival were curtailed by the large number of early losses, with only 52% of third grafts functioning at 1 year. For living related donor transplantation, parents were mostly used in children whilst identical siblings predominated in adults older than 45. In the early eighties, patient survival was 92% at 5 years for recipients younger than 15, 87% for the 15-45 year old cohort and 72% for those aged 45 or older.(ABSTRACT TRUNCATED AT 400 WORDS)
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We studied the geographical distribution, male to female ratio, and age at the start of renal replacement therapy (RRT) for end-stage renal failure (ESRF) in 600 patients with hereditary nephritis with nerve deafness (Alport's syndrome) reported to the European Dialysis and Transplant Association Registry since 1975. Annual age- and sex-specific acceptance rates for RRT showed a variable peak incidence according to country, ranging between, 0 and 2.4 patients per million population in males aged 15-24 years, but with only about half this incidence in females. In Scandinavian countries there were very few females who started RRT, and males were older than in the rest of Europe. The overall male to female ratio was 4:1. The median age at the start of RRT was: males (n = 479) 24.3 years (1st quartile 19.5 years; 3rd quartile 31.5 years); females (n = 121) 31.5 years (1st quartile 23.0 years; 3rd quartile 43.2 years). Our study provided confirmation that males reach ESRF earlier than females. In addition, we detected previously unrecognized geographical differences.