Long-Term (5 Years) Efficacy and Safety of Pancreas Transplantation Alone in Type 1 Diabetic Patients
ABSTRACT Although combined pancreas and kidney transplantation is an established procedure for the treatment of type 1 diabetes (T1D) in patients with end-stage renal disease, the role of pancreas transplant alone (PTA) in the therapy of T1D subjects with preserved kidney function is still matter of debate.
We report our single-center experience of PTA in 71 consecutive T1D patients all with a posttransplant follow-up of 5 years. Patient and pancreas (normoglycemia in the absence of any antidiabetic therapy) survivals were determined, and several clinical parameters (including risk factors for cardiovascular diseases) were assessed. Cardiac evaluation and Doppler echocardiographic examination were also performed, and renal function and proteinuria were evaluated.
Actual patient and pancreas survivals at 5 years were 98.6% and 73.2%, respectively. Relaparotomy was needed in 18.3% of cases. Restoration of endogenous insulin secretion was accompanied by sustained normalization of fasting plasma glucose concentrations and HbA1c levels as well as significant improvement of total cholesterol, low-density lipoprotein-cholesterol, and blood pressure. An improvement of left ventricular ejection fraction was also observed. Proteinuria (24 hours) decreased significantly after transplantation. One patient developed end-stage renal disease. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant glomerular filtration rate less than 90 mL/min.
PTA was an effective and reasonably safe procedure in this single-center cohort of T1D patients.
SourceAvailable from: Erika B Rangel[Show abstract] [Hide abstract]
ABSTRACT: Introduction: With further reduction in surgical complications and improvement in immunosuppressive protocols, pancreas transplant offers excellent outcomes for patients with diabetes. However, long-term survival of pancreas allograft is affected not only by rejection but also by immunosuppressive regimen toxicity. Areas covered: This article reviews the existing literature and knowledge of tacrolimus toxicity and focuses on its diabetogenic effect after pancreas transplant. Some clinically relevant drug-drug interactions with glucocorticoids and sirolimus are also highlighted. This review also summarizes the diabetogenic mechanisms of tacrolimus, the alternatives to minimize these effects, and the main differential diagnosis of hyperglycemia after pancreas transplant. Expert opinion: Tacrolimus is a potent calcineurin inhibitor, an important pathway that regulates pancreatic development. Tacrolimus can induce β-cell apoptosis, decrease insulin exocytosis and reduce insulin gene transcription, which ultimately lead to impaired functional β-cell mass after pancreas transplant. Furthermore, insulin resistance can exacerbate the diabetogenic effect of tacrolimus due to inhibition of insulin gene transcription and β-cell proliferation. It is important to critically analyze the results of clinical studies and investigate new immunosuppressive drugs and/or novel drug combinations. It is equally important to comprehend and interpret experimental data. Therefore, minimization of side effects, based on safe approaches, can prolong pancreas allograft survival.Expert Opinion on Drug Metabolism & Toxicology 09/2014; 10(11):1-21. DOI:10.1517/17425255.2014.964205 · 2.93 Impact Factor
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ABSTRACT: Pancreatic islet transplantation is a minimally invasive procedure that can restore normoglycemia and insulin independence in Type 1 diabetics without the surgical complications associated with vascularized pancreas transplantation. The advances made in this field over the past decade have dramatically improved patient outcomes, and the procedure is now transitioning from an experimental treatment to a clinical reality. Nonetheless, a number of important issues continue to hamper the success of islet transplantation and must be addressed before there is widespread clinical acceptance. These include the relative inefficiency of the islet isolation process, the progressive loss of islet function over time and the need for multiple donors to achieve insulin independence. Here, we discuss the current status of islet transplantation and examine its future as a treatment for Type 1 diabetes.Expert Review of Clinical Immunology 12/2014; 11(1):1-10. DOI:10.1586/1744666X.2015.978291 · 3.34 Impact Factor
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ABSTRACT: To facilitate endoscopic access for rejection surveillance and stenting of the pancreas, we have abandoned the duodenojejunostomy (DJ) in favor of duodenoduodenostomy (DD) in pancreas transplantation (PTx). From September 2012 to September 2013 we performed 40 PTx with DD; 20 solitary-PTx (S-PTx) and 20 simultaneous pancreas and kidney transplantation (SPK). We compared the outcomes with results from 40 PTx-DJ (10 S-PTx and 30 SPK) from the preceding era. The DD-enteroanastomoses were performed successfully. Endoscopic pancreas biopsies (endoscopic ultrasound examination [EUS]) yielded representative material in half of the cases. One exocrine fistula was treated by endoscopic stenting. PTxs-DD were associated with a higher rate of thrombosis compared to PTx-DJ (23% vs. 5%) and reoperations (48% vs. 30%), as well as inferior graft survival (80% vs. 88%). Time on waiting list, HLA A + B mismatches and reoperations were associated with graft loss. Only recipient age remained an independent predictor of patient death in multivariate analysis. PTx-DD showed a higher rate of thrombosis and inferior results, but facilitated a protocol biopsy program by EUS that was feasible and safe. Given that technical difficulties can be solved, the improved endoscopic access might confer long-term benefits, yet this remains to be proven.American Journal of Transplantation 11/2014; 15(1). DOI:10.1111/ajt.12953 · 6.19 Impact Factor