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Query: UMLS:C0011854 (type 1 diabetes)
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Combined renal and pancreatic transplantation in patients with juvenile diabetes mellitus, diabetic nephropathy and renal insufficiency is designed to improve the poor prognosis observed with hemodialysis or renal transplantation alone. Interest has recently shifted from pancreatic organ to islet transplantation, in view of the absence of complications with the latter. However, no permanent success with islet transplants in diabetic patients has so far been reported. In the series presented, one patient with juvenile diabetes and subsequent renal failure was successfully treated with simultaneous kidney and intrasplenic pancreatic islet allotransplants. One year after the operation the patient has normal blood glucose levels without exogenous insulin, despite treatment with prednisone.
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PMID:[Successful allotransplantation of an island of Langerhans]. 11 44

During a six year period twelve patients with insulin dependent diabetes and end-stage renal failure received cadaveric kidney grafts. Eleven of the patients have previous to this been hemodialysed, one patient was transplanted before hemodialysis was necessary. The cumulative two year survival was thirty-seven per cent for the patients, and twenty-nine per cent for the kidney grafts. The average time of observation was eleven months, the motality was fifty per cent. The causes of death were acute myocardial infarction in two cases, sepsis in two cases, severe hypoglycemia in one case and unexpected sudden death in one case. The most prominent problems in the treatment of the diabetic patients after the renal transplantation were difficulties in the regulation of the diabetes, rejections, infections, cardiac failure and aggravation in pre-existing hypertension.
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PMID:Renal transplantation in patients with insulin requiring diabetes and renal failure. 78 7

A procedure was developed in the laboratory for pancreatic allotransplantation in pancreatectomized dogs. Dogs with such grafts have survived for many months when treated with azathioprene and prednisone to prevent rejection. Contrary to usual beliefs, the pancreas is not unduly sensitive to total ischemia since it has been possible to successfully preserve a canine pancreas in vitro with hypothermia for periods up to 24 hours. Such preserved pancreas' have then been allotransplanted into pancreatectomized dogs with survival of the dogs for long periods. We have now done pancreaticoduodenal allotransplantation in 13 patients with juvenile onset diabetes mellitus. Nine of these patients also had renal failure and received simultaneously a renal allograft taken from the same cadaver. In all but one of these patients the pancreas functioned immediately. Two patients with juvenile onset diabetes mellitus and severe retinopathy but without terminal renal failure have received pancreaticoduodenal allografts alone. In both of these patients the pancreas functioned immediately but problems with the duodenum necessitated the removal of the pancreaticoduodenal allograft which did not show signs of rejection. As a result of the findings of increased sensitivity of the kidney and duodenum to rejection we have now modified our technique to transplant the pancreas alone. This technique was used in one patient with juvenile onset diabetes mellitus and severe retinopathy. Her renal function was only moderately reduced. The pancreatic allograft initially functioned normally but then was removed at 28 days because of clinical signs of rejection of the pancreas which were confirmed by the microscopic findings. Despite the promise of islet-cell transplantation, no long term functioning allografts have resulted in animals or man. Thus we need to continue with whole organ pancreatic allografts by various techniques if diabetes mellitus is to be controlled.
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PMID:Transplantation of the pancreas. 82 66

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.
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PMID:Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy. 131 15

Points of agreement: (1) In IDDM, hypertension occurs in patients who have already developed nephropathy, probably in the microalbuminuric phase. (2) Hypertension is an important accelerator of the development of diabetic nephropathy. (3) Hypertension, obesity and NIDDM are often associated, and insulin resistance is commonly observed in all three states. (4) Antihypertensive therapy retards the development of diabetic nephropathy in IDDM and reduces proteinuria in NIDDM. (5) The choice of antihypertensive agent in the diabetic patient must be based upon the efficacy of the drug as well as avoidance of side effects including deleterious influence on glucose, insulin and lipid levels and renoprotection. (6) Carefully conducted long-term comparative trials between different classes of antihypertensive drugs in microalbuminuric IDDM and NIDDM patients are essential. Points of major controversy: (1) Detection of IDDM patients prone to the development of diabetic nephropathy can be performed by measuring specific parameters such as erythrocyte Na(+)-Li+ countertransport activity. (2) Insulin resistance is a pathogenic mechanism rather than purely an association with hypertension and obesity. (3) A certain class of antihypertensive agents--ACE inhibitors--confers a specific renoprotective effect in diabetic nephropathy, in addition to its effects upon systemic blood pressure. (4) Reduction of blood pressure should be considered in the normotensive microalbuminuric diabetic patient. (5) Microalbuminuria is a sufficient 'surrogate endpoint' for the progression of renal failure.
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PMID:Meeting report of the International Society of Hypertension Conference on Hypertension and Diabetes. 131 6

The prevalence of diabetes mellitus among patients treated for end-stage renal failure was studied using a questionnaire mailed to all dialysis units of mainland France in 1989. With a response rate of 80.8%, the study population amounted to 12,903 dialysed patients of whom 884 were declared diabetic (6.9%). In a second phase, the study focused on the diabetic patients treated in the 63 largest units (those with at least four diabetic patients). Seven specially trained physicians completed questionnaires after having interviewed the patients and checked their medical records. All this material was reviewed by the same diabetologist. The conflict of diabetes type declared by both sources of information (the nephrologists and the diabetologist) showed a misclassification rate of 31.2%. Using these new data, the prevalence of type 1 diabetes mellitus was estimated at 1.4% of patients on dialysis therapy in mainland France, and 5.5% for type 2 diabetes mellitus. A north-south declining trend was suggested for type 2 diabetes mellitus. Diabetic nephropathy was the only primary renal diagnosis among 93.9% of type 1 diabetic patients, but only for 36.8% of type 2 diabetic patients. Of the latter, 51.6% had a non-diabetic cause of renal failure. These data show that the proportion of diabetics among patients receiving dialysis, while steadily increasing in France, remains lower than in other countries in Europe and in North America. However, the validity of international comparisons depends on diabetes ascertainment. Heterogeneity in selection of patients and in diabetes type classification by dialysis units may account to a considerable degree for the differences between diabetes mellitus prevalence across countries.
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PMID:Diabetes mellitus prevalence among dialysed patients in France (UREMIDIAB study). 133 35

In 1992, transplantation of the endocrine pancreas is placed at the interface between laboratory research and clinical medicine. Unlike other forms of transplantation, it is not life saving, and yet its potential to treat all patients with insulin dependent diabetes is limited only by the availability of donated organs. Arguably, the long term glucose homoeostasis provided by vascularised pancreas transplantation is the standard by which other forms of endocrine pancreas transplantation (islet cell, fetal islet, and xenogeneic transplantation) must be judged. For the small number of type I diabetic Australians who develop end-stage renal failure and would otherwise require a renal transplant, the combined transplant procedure is a technically viable treatment option and, with some justification, the treatment of choice.
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PMID:Transplantation of the endocrine pancreas in 1992. 140 13

As many as 34 patients with nephrotic syndrome (NS) and 42 patients suffering from type I diabetes mellitus without clinical manifestations of renal damage were examined for clinical and morphological signs of hyperperfusion renal damage (hyperfiltration, microalbuminuria, specific morphological alterations). The lack of renal functional reserves was regarded as a criterion for the status of hyperfiltration (oral protein administration, intravenous injection of small doses of dopamine). The risk of the progression of renal failure by the hemodynamic type in NS amounted to 65%. In the mechanism of the development of hyperfiltration in NS, the role of systemic hypertension, renal failure, a reduction of the ultrafiltration coefficient is discussed. Hypooncia does not make any material contribution to the development of hyperfiltration in NS. The clinical and morphological signs of hyperfusion renal injury were revealed in 50% of patients suffering from type I diabetes mellitus without the clinical signs of renal injury.
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PMID:[Hyperfiltration as a factor in the progression of chronic kidney diseases]. 144 Mar 23

Renal failure was found in a five-year-old patient who had been treated with insulin since he was diagnosed as having insulin dependent diabetes mellitus (IDDM) at 3 years of age. Laboratory data showed that his renal failure was caused by a renal tubular dysfunction. The autopsy findings of his pancreas were compatible with those of IDDM. The kidneys were atrophied with an innumerable number of crystals in the proximal tubuli. Staining by Kossa indicated that the crystals contained calcium salt. The calcium content of his kidneys was significantly higher than that of control. The nephrocalcinosis seems to be caused by hypercalciuria associated with IDDM.
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PMID:Insulin dependent diabetes mellitus accompanied by nephrocalcinosis and renal failure. 144 54

We analyzed the overall results of 24 simultaneous pancreas and kidney transplantations (SPK), performed in our hospital between April 1986 and June 1990. All patients had type I diabetes mellitus and end-stage renal failure. We used bladder drainage of the pancreatic exocrine secretions through a duodenocystostomy. The blood vessels of both grafts were anastomosed to the iliac vessels. The immunosuppressive management was triple-therapy with cyclosporin, azathioprine and prednisone. All organs were transplanted without matching donors and recipients for HLA. At the time of transplantation, mean recipient age was 37 yr; the average duration of diabetes was 22 yr. After disappointing results in the first 4 patients, the pancreas was placed intraperitoneally instead of extraperitoneally and the antibiotic drug regimen was altered. In the second group (n = 20), patient survival was 100%; 1-yr pancreas and kidney graft survival were 65 and 62%, respectively. Duration of hospitalization and pancreas and kidney graft loss were positively correlated with the number of rejection episodes. After 1 yr of follow-up, the mean creatinine clearance was 62 ml/min and the mean HbA1c was 5.5%. Blood glucose levels and oral glucose tolerance tests were also normal. We conclude that patient and graft survival after SPK are satisfactory, although rejection-related morbidity is still a major problem.
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PMID:Simultaneous pancreas and kidney transplantation: a feasible procedure in selected patients. 149 98


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