Introduction
Background
The purpose of pancreas transplantation is to ameliorate type I diabetes and produce complete insulin independence. The first successful pancreas transplantation in conjunction with a simultaneous kidney transplantation was performed by Richard Lillehei, MD, from the University of Minnesota in 1966. Until about 1990, the procedure was considered experimental. Now it is a widely accepted therapeutic modality, with virtually all insurance carriers covering the procedure, including Medicare. The pancreas comes from a cadaveric organ donor. However, select cases of living-donor pancreas transplantations have been performed. About 100 transplant centers in the United States perform pancreas transplantations. About 1400 cases are performed annually in the United States.
About 75% of pancreas transplantations are performed with kidney transplantation (both organs from the same donor) in patients with renal failure who are diabetic. This is referred to as a simultaneous pancreas-kidney (SPK) transplantation. About 15% of pancreas transplantations are performed after a previously successful kidney transplantation. This is referred to as a pancreas-after-kidney transplantation. The remaining 10% of cases are performed as pancreas transplantation alone in nonuremic patients with very labile and problematic diabetes. An alternative new therapy that may also ameliorate diabetes is islet transplantation, which is experimental and is not yet as efficient as pancreas transplantation.
Pathophysiology
Type I diabetes mellitus is an autoimmune disease wherein the insulin-producing pancreatic beta cells are destroyed selectively. Presently, no practical mechanical insulin-delivery method exists that, coupled with an effective glucose-sensory device, replaces pancreatic insulin secretion well enough to produce a near constant euglycemic state without risk of hypoglycemia. Therefore, individuals with type I diabetes must resign themselves to manual regulation of blood glucose levels by subcutaneous insulin injection and, as a consequence, typically exhibit wide deviations of plasma glucose levels from hour to hour and from day to day.
Hyperglycemia is the most important factor in the development and progression of the secondary complications of diabetes. These observations, and the fact that conventional exogenous insulin therapy cannot prevent the development of secondary complications of type I diabetes, have led to a search for alternative methods of treatment.
One such treatment, pancreas transplantation, has the potential to achieve better glycemic control and alter the progression of long-term complications. A successful pancreas transplantation produces a normoglycemic and insulin-independent state. It reverses the diabetic changes in the native kidneys of patients with very early diabetic nephropathy, prevents recurrent diabetic nephropathy in patients undergoing an SPK transplantation, reverses peripheral sensory neuropathy, stabilizes advanced diabetic retinopathy, and significantly improves patients' quality and quantity of life.
The insulin released by the endocrine pancreas graft is secreted into the blood stream. Because the exocrine pancreas produces about 800-1000 mL per day of fluid, it must be diverted in either the bladder or bowel. If the pancreas graft is attached to the bladder, the losses of pancreatic fluid rich in bicarbonate may produce relative acidosis. This usually is treated by bicarbonate supplementation. Because the pancreas graft comes from another individual, the recipient's immune system can mount a rejection reaction and destroy the graft. To prevent that problem, immunosuppression medications must be taken daily and forever to prevent rejection. Chronic immunosuppression elevates the risk of viral and fungal infections and some types of malignancy.
Frequency
United States
Currently, the prevalence of type I diabetes in the United States is estimated to be 1,100,000 individuals, and 35,000 new cases are diagnosed each year. The total annual cost of diabetes, including hospital and physician care, laboratory tests, pharmaceutical products, and patient workdays lost because of disability and premature death, exceeds $90 billion.
Only about 1,200 pancreas transplantations are performed each year. The number is limited by the number of cadaveric organs available for transplantation. Candidates for the procedure have type I diabetes and generally are aged 55 years or younger. Ninety-five percent of pancreas transplantations are performed in patients with renal disease or a previous functioning kidney transplant. The recipients must be healthy to undergo the surgical procedure. Therefore, the pretransplantation workup emphasizes diagnosis of significant cardiovascular disease, established nontreatable infectious disease, and cancer.
Mortality/Morbidity
At the turn of the century, a patient diagnosed with type I diabetes mellitus had an average life expectancy of only 2 years. The development of insulin as a therapeutic agent revolutionized the treatment of diabetes mellitus by changing it from a rapidly fatal disease to a chronic illness. Unfortunately, this increased longevity allowed the development of secondary complications, including nephropathy, neuropathy, retinopathy, and macrovascular and microvascular complications, occurring 10-20 years after disease onset.
Pancreas transplantation results are reported to the Scientific Registry of Transplant Recipients (SRTR) of the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR). Based on this information, the national 1-year patient, kidney, and pancreas survival rates for recipients of an SPK transplant are 95%, 91%, and 86%, respectively. Compared to patients with diabetes who receive a kidney alone, the addition of a pancreas improves long-term patient and kidney graft survival.1 Recipients of a pancreas-after-kidney transplant or a pancreas transplant alone have an average 1-year pancreas graft survival rate of 78-83%.
Clinical
History
Evaluation of candidates for pancreas transplantation involves the following:
- Renal disease: Preexisting advanced renal disease is observed in significant numbers of pancreas transplantation candidates. Therefore, coincident extrarenal disease should be assumed present.
- Diabetic retinopathy: Diabetic retinopathy is a ubiquitous finding in patients with diabetes and end-stage renal disease (ESRD). Significant vision loss may be observed. Also, patients may be overtly blind. Blindness is not an absolute contraindication to transplantation because many blind patients lead very independent lives. Although rarely a problem, confirm that a patient with significant vision loss has an adequate support system to ensure help with travel and immunosuppressive medications.
- Gastroparesis: Impaired gastric emptying (gastroparesis) is an important consideration because of its significant implications in the posttransplantation course. Patients with severe gastroparesis may have difficulty tolerating oral immunosuppressive medications that are essential to prevent rejection of the transplants. Episodes of volume depletion with associated azotemia frequently occur in patients with SPK transplants. Patients typically require careful treatment, including motility agents such as metoclopramide, cisapride, or erythromycin.
- Coronary artery disease: The most important comorbidity to consider in patients with type I diabetes with diabetic nephropathy is coronary artery disease (CAD). Patients with diabetes and ESRD are estimated to carry a nearly 50-fold greater risk of cardiovascular events than the general population. This type of patient may have several risk factors in addition to diabetes for development of CAD, including hypertension, hyperlipidemia, and smoking. Because of neuropathy associated with diabetes, patients may have asymptomatic myocardial ischemia-induced angina. The prevalence of significant (>50% stenosis) CAD in patients with diabetes who are starting treatment for ESRD is estimated to be 45-55%.
- Stroke: Patients with ESRD and diabetes also experience an increased rate of strokes and transient ischemic attacks. Deaths related to cerebral vascular disease are approximately twice as common in patients with diabetes compared to patients without diabetes once ESRD has occurred. Patients with diabetes experience strokes more frequently and at a younger age than do age- and gender-matched nondiabetic patients with stroke.
- Peripheral vascular disease: Lower extremity peripheral vascular disease is significant in patients with diabetes. Patients with ESRD are at risk for amputation of a lower extremity. These problems typically begin with a foot ulcer associated with advanced somatosensory neuropathy.
- Autonomic neuropathy
- Autonomic neuropathy is prevalent and may manifest as gastropathy, cystopathy, and orthostatic hypotension. The extent of diabetic autonomic neuropathy commonly is underestimated.
- Neurogenic bladder dysfunction is an important consideration in patients undergoing bladder-drained pancreas-alone transplantation or SPK transplantation. Inability to sense bladder fullness and empty the bladder predisposes to high postvoid residuals and the possibility of vesicoureteral reflux. This may affect renal allograft function adversely, increase the incidence of bladder infections and pyelonephritis, and predispose to graft pancreatitis.
- The combination of orthostatic hypotension and recumbent hypertension results from dysregulation of vascular tone. This has implications for blood pressure control following transplantation, especially in patients with bladder-drained pancreas transplants who are predisposed to volume depletion. Therefore, careful reassessment of the posttransplantation antihypertensive medication requirement is important.
- Sensory and motor neuropathies: These conditions are common in patients with longstanding diabetes. This may have implications for rehabilitation after transplantation. It also is an indicator for potential risk of injury to the feet and subsequent diabetic foot ulcers.
- Mental or emotional illnesses: Mental illnesses, including neuroses and depression, are common. Diagnosis and appropriate treatment of these illnesses is an important pretransplantation consideration, with important implications for ensuring a high degree of medical compliance. For more information on the treatment of depression, please visit Medscape's Depression Resource Center.
Causes
Type I diabetes is an autoimmune disease that results in selective loss of the insulin-producing beta cells of the islets of Langerhans. No reliable way to predict who will develop diabetes is available, nor does a cure exist. Transplantation of the pancreas is a treatment option designed to replace the islets. Immunosuppression to prevent organ rejection is sufficient also to prevent recurrent autoimmune diabetes.
More on Pancreas Transplantation |
 Overview: Pancreas Transplantation |
| Differential Diagnoses & Workup: Pancreas Transplantation |
| Treatment & Medication: Pancreas Transplantation |
| Follow-up: Pancreas Transplantation |
| Multimedia: Pancreas Transplantation |
| References |
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References
Hakim NS. Recent developments and future prospects in pancreatic transplantation. Exp Clin Transplant. Jun 2003;1(1):26-34. [Medline].
Demartines N, Schiesser M, Clavien PA. An evidence-based analysis of simultaneous pancreas-kidney and pancreas transplantation alone. Am J Transplant. Nov 2005;5(11):2688-97. [Medline].
Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. Clin Transplant. Aug 2005;19(4):433-55. [Medline].
Ojo AO, Meier-Kriesche HU, Hanson JA, et al. The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation. Jan 15 2001;71(1):82-90. [Medline].
United Network for Organ Sharing (UNOS). United Network for Organ Sharing (UNOS). [Full Text].
Further Reading
Keywords
pancreas transplantation, pancreas allotransplantation, simultaneous pancreas-kidney transplantation, SPK, type 1 diabetes, insulin independence, pancreas-after-kidney transplant, islet transplant, pancreatitis, enteric-drained
