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Query: UMLS:C0011881 (diabetic nephropathy)
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In theory, transplantation of the islets of Langerhans is the method of choice for the treatment of insulin-dependent diabetes. In actual fact, medical teams who have been working on this subject for about two decades have met with the problem of islet isolation, and for the time being this treatment cannot be considered effective. Pancreas transplantation gives satisfactory results in diabetics with renal impairment when it is coupled with kidney transplantation. However, it cannot yet be applied to all diabetics as its results are mediocre when performed alone, and it requires chronic immunosuppression. Pancreas transplantation not only increases the quality of life but also has the advantage of acting on degenerative complications: it may improve diabetic nephropathy, retinopathy and neuropathy. The results obtained are getting better year after year, and they are now close to those observed with other organ transplantations.
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PMID:[Islets of Langerhans grafts and pancreas transplantation]. 149 35

The significance of portal venous drainage after whole-pancreas transplantation both for metabolic control and development of diabetic nephropathy was investigated. Streptozotocin-diabetic inbred LEW rats received a duct-ligated pancreas graft with either systemic or portal venous drainage and were followed for up to one year. Normal and untreated diabetic rats (n=18 in each group) served as controls. Irrespective of the route of venous drainage pancreas transplants normalized the diabetic polyuria, polyphagia, and polydipsia. Growth rates and general health did not differ from normal rats. Pancreas transplantation with portal venous drainage furthermore normalized nonfasting blood glucose and peripheral insulin levels, and intravenous glucose tolerance. Pancreas transplantation with systemic venous drainage, however, was associated with peripheral hyperinsulinemia, slightly elevated nonfasting blood glucose levels, and supranormal K-values in intravenous glucose tolerance tests. Though portal venous drainage was associated with better metabolic control than systemic venous drainage, both techniques of pancreas transplantation proved equally effective to prevent the development of diabetic glomerular membrane thickening determined 6 and 12 months posttransplant.
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PMID:Significance of portal venous drainage after whole-organ pancreas transplantation for endocrine graft function and prevention of diabetic nephropathy. 240 87

Pancreas transplantation is performed to establish a normoglycemic state, insulin-independent, in a diabetic type I recipient. Abundant evidence supports the concept that lesions developing in the eyes, nerves, kidneys and other organ systems are secondary to disordered metabolism and that restoration of normoglycemia will favorably influence their evolution. The need to provide antirejection, therapy currently confines the application of pancreas transplantation to three main groups of recipients: 1. patients who need a kidney transplant to treat end-stage diabetic nephropathy, 2. patients who received a renal transplant and have progressive systemic diabetic disease, 3. diabetics who are severely handicapped in their day-to-day lives because of difficulty with metabolic control. A significant improvement in the results of pancreas transplant has progressively occurred worldwide and several controlled studies are beginning to provide evidence of the favorable effect on secondary complications. The quality of life of these patients is also improved by a functioning graft.
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PMID:[Pancreas transplantation]. 250 20

To examine whether plasma and urine concentrations of human atrial natriuretic peptide (hANP) are altered in patients with diabetes mellitus (DM), plasma and urine hANP concentrations were evaluated in 86 patients with diabetes mellitus using an extraction procedure. The mean recovery rate of extraction was 71.8 +/- 0.6% (mean +/- SEM). The major immunoreactive component of hANP in extracted plasma and urine appeared to be identical to synthetic alpha hANP as judged by reverse-phase high-performance liquid chromatography (HPLC). The patients were divided into three groups according to their renal complications. The patients in group 1 had no apparent abnormality in serum creatinine, serum or urine beta 2-microglobulin (beta 2-MG), or urine N-acetyl-beta-D-glucosaminidase (NAG); those in group 2 showed either beta 2-MG or NAG abnormality but no creatinine abnormality. The patients in group 3 were though to have an established diabetic nephropathy and showed a serum creatinine increase. Plasma ANP concentrations in groups 1, 2, and 3 were 10.7 +/- 2.1, 19.9 +/- 5.6, and 39.2 +/- 9.9 fmol/ml, respectively. These values in groups 2 and 3 were significantly higher than the control values (p less than 0.05 or p less than 0.01 versus 6.2 +/- 0.7 fmol/ml). Urine ANP concentrations in group 1 were also within normal range, though those in groups 2 and 3 markedly increased in comparison with normal values.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1988
PMID:Plasma and urine concentrations of atrial natriuretic peptide in patients with diabetes mellitus. 297 69

Kidney transplantation is now firmly established as the standard treatment for all diabetic patients with end-stage renal failure. In an analysis of all renal transplants at the University of Minnesota between June 1, 1980 and May 31, 1987, there were no differences in renal allograft functional survival rates for diabetic and nondiabetic recipients. At one year the survival rates were 84% (n = 151) and 86% (n = 260) for those treated with azathioprine, prednisone and ALG; 86% (n = 101) and 87% (n = 104) for those treated with cyclosporine-prednisone, and 92% (n = 165) and 89% (n = 191) for those treated with triple therapy (cyclosporine, azathioprine, and prednisone). Pancreas transplantation remains an investigational procedure for nonuremic diabetic patients but may be considered therapeutic in diabetic renal allograft recipients because such patients are obligated to immunosuppression and only the surgical risks of pancreas transplantation need to be considered, which are now acceptably low. Recipients of pancreas transplants performed simultaneous with the kidney have patient and pancreas graft survival rates of greater than 90% and +/- 60% at several institutions, including our own. The potential for benefit of pancreas transplantation, however, is greater in the nonuremic nonkidney transplant patient, and pancreas transplantations are being performed in such patients at a few institutions. An early beneficial effect of pancreas transplantation preexisting proliferative retinopathy has not been discerned, although long-term retinopathy has been stable in patients with functioning grafts. Preliminary studies have shown a beneficial effect on neuropathy and on microscopic lesions of diabetic nephropathy, but at the expense of cyclosporine toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal transplantation in diabetic patients is confirmed therapy while pancreas transplantation should be performed only in an investigational setting. 297 67

Most candidates for pancreatic transplantation have end-stage diabetic nephropathy (ESDN) and receive a pancreas transplant either sequential to or simultaneous with a renal transplant. Because ESDN is often associated with severe irreversible neurovascular complications, the selection of these candidates may defeat the intent of pancreatic transplantation, i.e., the reversal, stabilization, or retardation of neurovascular complications. Also, advanced neurovascular complications in these candidates may result in serious morbidity and mortality after pancreatic transplantation. Our multidisciplinary Pancreas Transplant Evaluation Committee has developed tentative candidate criteria for insulin-dependent diabetic patients before ESDN. With the proposed criteria, candidates are selected who have predictors of future morbidity and mortality but who do not yet demonstrate irreversible neurovascular complications and an inexorable general course of deterioration. As pancreatic transplantation becomes more successful, candidate criteria must be continually reassessed to better identify those who may obtain maximal benefit.
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PMID:Pancreatic transplantation as treatment for IDDM. Proposed candidate criteria before end-stage diabetic nephropathy. The University of Michigan Pancreas Transplant Evaluation Committee. 250 44

In summary, at the University of Minnesota we perform pancreas transplants from both living-related and cadaver donors. Living-related donors must meet strict criteria indicating that they are not at risk for diabetes. Segmental grafts are procured from living-related donors. We currently procure whole pancreas grafts from most cadaver donors, including those in whom a liver is procured. We will accept preservation times up to 24 hours using hyperosmolar silica-gel-filtered plasma as the preservation solution. In regard to recipient selection, we have several categories of patients, including nonuremic individuals with early secondary lesions of diabetes affecting the eyes, nerves, and kidneys. Pancreas transplants are also performed in patients with end-stage diabetic nephropathy, either simultaneous with or after a kidney transplant. The potential benefit from pancreas transplantation is greatest in patients who have early diabetic complications which in the absence of this intervention would progress to a severity more serious than the possible side effects of chronic immunosuppression. A careful pretransplant evaluation is necessary in order to select nonuremic, nonkidney recipients in whom pancreas transplantation is appropriate. The selection process is much easier in kidney transplant recipients; virtually any person who can withstand the additional surgery is a candidate, the risks associated with immunosuppression having already been accepted in lieu of the unsatisfactory alternative of chronic dialysis. The results we have obtained in the 3 categories of recipients since November 1984 in patients managed by our currently preferred surgical techniques and immunosuppressive protocols are shown in Figure 6. One-year pancreas survival rates in nonuremic, nonkidney transplant recipients are 63%, in recipients of a previous kidney 46%, and in recipients of simultaneous kidneys 75%. With respect to surgical technique, our current preference is the bladder drainage method because the ability to monitor exocrine function leads to earlier diagnosis and treatment of rejection episodes. With related donor transplant, we have continued to use enteric drainage. Because the rejection rate is much lower than with cadaver donors, the one-year functional survival rate has been relatively high for technically successful enteric-drained related donor grafts. Nevertheless, rejection does occur, and related donor segmental grafts are being performed with bladder drainage. Our current immunosuppressive protocol of quadruple drug therapy has been associated with the highest graft survival rates, particularly in the bladder-drained group where early diagnosis and treatment of rejection has been facilitated. In our experience, UAA monitoring results have had a high correlation with rejection episodes, and we have never seen loss of endocrine function with retention of high UAA levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pancreas transplant protocols at the University of Minnesota: recipient and donor selection, operative and postoperative management, and outcome. 315 73

From December 1966 through December 1984, there were 561 pancreas transplants reported to the American College of Surgeons/National Institutes of Health Organ Transplant Registry, including 60 from 1966 through June 1977, 206 from July 1977 through December 1982 and 295 from January 1983 through December 1984. One-year graft function-survival rates (insulin-independent) in each of the three periods were 3%, 20% and 40%, and the corresponding patient survival rates were 40%, 72% and 77%. Currently 140 patients have functioning grafts, 76 for more than one year. Of the transplants since July 1977, one-year graft survival rates according to technique are 41% for enteric drainage (N = 155), 30% for polymer injection (N = 260) and 29% for urinary drainage (N = 47). Pancreas graft survival rates at one year according to whether or not the recipients have had a kidney transplant were 35% for recipients of simultaneous grafts (N = 281), 28% in recipients of a pancreas after a kidney (N = 112) and 26% in recipients of a pancreas only who did not have uremia (N = 106); corresponding patient survival rates were 69%, 83% and 83%. Overall, one-year pancreas graft survival rates according to whether the patients did or did not have end-stage diabetic nephropathy were 33% versus 25% and the corresponding patient survival rates were 73% versus 84% (P < .01). Patient survival rates were significantly higher in those without than in those with end-stage diabetic nephropathy. An analysis of technically successful grafts according to principal immunosuppressant showed one-year function rates of 46% in 258 cyclosporine-treated recipients and 26% in 143 azathioprine-treated recipients. Pancreas graft survival rates have progressively improved and the procedure has become safer with advances in surgical technique and immunosuppression. Pancreas transplantation is currently applicable to patients with diabetes mellitus whose complications are, or predictably will be, more serious than the possible side effects of long-term immunosuppression.
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PMID:Pancreas transplantation--registry report and a commentary. 391 97

Clinical pancreas transplantation at the University of Minnesota began in 1966. An initial series of 14 whole pancreas grafts was reported in part to the American Surgical Association in 1970. Only one patient survived for more than 1 year with a functioning graft. Twenty attempts at islet allotransplantation in the mid-1970s were unsuccessful. In 1978 we resumed performing pancreas transplants by the segmental technique, allowing the use of related donors. The current series (July 25, 1978 to December 20, 1983) includes 86 pancreas transplants (51 cadaver, 35 related) in 75 patients (41 with and 34 without previous kidney grafts). Variations in management of the pancreatic duct include three ligated, 15 duct-open, 39 duct-injected, and 29 pancreaticojejunostomies. The latter technique is currently preferred. Currently (April 1984) 61 patients are alive (81%), 24 have functioning grafts (32%), and 21 are insulin-independent (28%), three with open-duct grafts for 4.4 to 5.7 years, seven with silicone-injected grafts from 10 to 39 months, and 14 with pancreaticojejunostomies for 3 to 31 months; 15 of the grafts have functioned for greater than 1 year. Twenty-two of the grafts (25%) failed for technical reasons (thrombosis, infection, or ascites); 35 grafts functioned for 1 to 13 months before totally failing from either rejection, fibrosis, or recurrent disease; five patients died with functioning grafts. The graft survival rate has been higher for pancreases from related (15/35, 43% functioning) than from cadaver (9/51, 18% functioning) donors. The success rate has increased, e.g., 11/22 recipients of pancreas transplants in 1983 currently have functioning grafts (50%). Metabolic studies show most patients with functioning grafts to be euglycemic; however, three of 24 have chronic hyperglycemia unless supplemented with insulin, but they are no longer ketosis-prone. Glucose tolerance test results are normal or nearly normal in 12 and abnormal in 12 of the recipients with currently functioning grafts. Regression of diabetic nephropathy has been documented in two long-term recipients. Pancreas transplantation is currently applicable as treatment for selected diabetics who have demonstrated their propensity to develop serious secondary complications.
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PMID:One hundred pancreas transplants at a single institution. 638 74

Pancreas transplantation prevents or retards development of early diabetic glomerular lesions in renal allografts transplanted to patients with insulin-dependent diabetes mellitus (IDDM), but its effect on established renal lesions in native kidneys of such patients is unknown. Renal biopsy samples were taken before and 5 years after pancreas transplantation from 13 non-uraemic IDDM patients and compared with baseline and 5-year biopsy samples from 10 persistently hyperglycaemic IDDM patients who did not undergo transplantation. The two groups were similar in age, duration of diabetes, metabolic control, renal function, and blood pressure. Glomerular structures were measured by standard morphometric techniques. Haemoglobin A1 concentrations fell to within the normal range after pancreas transplantation but did not change in the comparison group. Glomerular basement membrane width did not significantly change in either group. Glomerular volume decreased and mesangial fractional volume increased in the pancreas transplant recipients but there was no significant change in total mesangial volume over 5 years. By contrast, both glomerular volume and mesangial fractional volume increased in the comparison patients, resulting in increased total mesangial volume. Diabetic glomerular lesions in patients with their own kidneys were not ameliorated by pancreas transplantation, despite 5 years of normoglycaemia. Pancreas transplantation can correct severe metabolic instability and thus improve quality of life, but it cannot yet be recommended for the treatment of established lesions of diabetic nephropathy.
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PMID:Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. 790 56


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