Selection Criteria for and Outcomes of Pancreatic Transplantation?

Robert J. Stratta, MD


October 19, 2000


I am an internist. I have a patient with diabetes mellitus type 1 of over 10 years duration. Could you give me details on the current status of pancreatic transplantation with regards to patient selection criteria and outcomes. Also, which center in southern California is most active in pancreatic transplantation?

V.S. Nayak, MD

Response from Robert J. Stratta, MD

Pancreas transplantation (PTX) was first developed as a means to achieve normal insulin secretion and is currently the only known therapy that reliably establishes an insulin-free state with complete normalization of glucose metabolism. With improvements in organ retrieval technology, refinements in surgical techniques, advances in clinical immunosuppression, and experience in donor and recipient selection, success rates for PTX have steadily increased. From 1966 through July of 2000, over 14,000 PTXs were performed worldwide. The majority (87%) of PTXs were performed in conjunction with a simultaneous kidney transplant (SKPT) in diabetic individuals who had advanced nephropathy (preemptive) or who were already on dialysis. The remaining PTXs were performed as a sequential pancreas after kidney transplant (PAKT, 9% of cases) or as a PTX alone (PTA, 4% of cases).

The total number of PTXs in the United States has steadily increased in the past few years, reaching over 1500 in 1999. In the past decade, the number of solitary PTXs (PAKT and PTA) has increased from about 60 to over 300 per year. The proportion of solitary PTXs has likewise increased and currently represents 15% to 20% of PTX activity in the United States. At present, the overall 1-year patient survival rate for all types of PTXs in the United States is 95%, and the 1-year pancreas graft survival rates (defined as complete insulin independence) are 86% after SKPT, 75% after PAKT, and 70% after PTA. The 1-year kidney graft survival rate after SKPT is 90%.

As of July 1, 1999, Medicare began to provide coverage for SKPT and PAKT. There is currently a bill in Congress to secure Medicare coverage for PTA and islet transplantation. SKPTs are performed routinely at many transplant centers and are an excellent treatment option for diabetics (both type 1 and type 2) who would benefit from a kidney transplant. The most active PTX centers in southern California include (in no particular order) University of California at Los Angeles, University of California at San Diego, St. Vincent, and Loma Linda. However, solitary PTXs (especially PTA) are not performed routinely at many PTX centers, and I am not aware of any center on the west coast that has a large experience in solitary PTX. The most active centers in solitary PTX include the University of Minnesota, University of Maryland, University of Tennessee-Memphis, and Northwestern University. This may be of particular relevance for the patient that you describe.

Standard eligibility guidelines for PTX include the presence of insulin-requiring diabetes mellitus (usually, but not exclusively type 1 diabetes), the predicted ability to withstand the operative procedure and possible associated complications, the predicted ability to tolerate (and comply with) the requisite chronic immunosuppression, and the absence of any exclusion criteria. As results have improved, previous absolute exclusion criteria have become relative contraindications, and relative contraindications have become mere risk factors for PTX.

Absolute contraindications include:

1. Insufficient cardiovascular reserve, with either coronary angiographic evidence of significant noncorrectable or untreatable coronary artery disease, or recent myocardial infarction;

2. Active infection;

3. History of malignancy treated within the past 3 years (excluding nonmelanoma skin cancer);

4. Positive HIV serology;

5. Positive hepatitis B surface antigen serology;

6. Active, untreated peptic ulcer disease;

7. Ongoing substance abuse (drug or alcohol);

8. Major ongoing untreated psychiatric illness;

9. Recent history of medical noncompliance;

10. Inability to provide informed consent;

11. Any systemic illness that would severely limit life expectancy or compromise recovery;

12. Significant, irreversible hepatic or pulmonary dysfunction;

13. Positive lymphocytotoxic cross-match.

Relative contraindications for PTX include:

1. Age less that 18 or greater than 65 years;

2. Recent retinal hemorrhage;

3. Symptomatic cerebrovascular or peripheral vascular disease;

4. Absence of appropriate social support network;

5. Extreme obesity (greater that 150% ideal body weight);

6. Active smoking;

7. Severe, untreatable peripheral vascular (aorto-iliac) disease.

Risk factors for PTX include:

1. History of myocardial infarction, congestive heart failure, or previous open heart surgery;

2. History of major amputation or peripheral bypass graft;

3. History of cerebrovascular event or carotid endarterectomy;

4. History of hypercoagulable syndrome.

A pretransplant medical evaluation is performed to document adequate cardiac and pulmonary function, to determine the presence and severity of diabetic complications, and to establish the absence of any exclusion criteria. The primary determinants for recipient selection are the presence of diabetic complications, degree of nephropathy, and cardiovascular risk.

Indications for PTX include:

1. Presence of insulin-requiring diabetes mellitus;

2. Ability to withstand surgery and immunosuppression (as assessed by pretransplant medical evaluation);

3. Adequate cardiopulmonary function;

4. Absence of other organ system failure (other than kidney);

5. Emotional and sociopsychological suitability;

6. Presence of well-defined diabetic complications (any 2):

  • Proliferative retinopathy

  • Nephropathy (with hypertension, proteinuria, or decline in glomerular filtration rate)

  • Symptomatic peripheral or autonomic neuropathy

  • Microangiopathy

  • Accelerated atherosclerosis

  • Glucose hyperlability, insulin resistance, or hypoglycemia unawareness causing a significant impairment in quality of life.

7. Specific entry criteria based on degree of nephropathy:

  • SKPT: creatinine clearance below 30 mL/min

  • Sequential PAKT: creatinine clearance above 40 mL/min

  • PTA: creatinine clearance above 60 mL/min.

Ideally, PTX should be performed before diabetic complications are present and before the need for a kidney transplant. At present, there are no reliable early markers to predict, before the earliest complications appear, which diabetic individuals are at risk for progressive complications. Solitary PTA is restricted by necessity to diabetic patients who have demonstrated a propensity to diabetic complications that are (or predictably will be) worse than the potential side effects of chronic immunosuppression. In addition, diabetic patients with repeated episodes of ketoacidosis, hypoglycemia unawareness, or glucose hyperlability may benefit from a PTA. PTA in this setting can immediately enhance a person's quality of life simply by achieving an insulin-free state. Most PTX recipients find the transition to transplantation easier than continued insulin therapy. In addition to improving quality of life, there is now compelling evidence that PTX is not only life-enhancing, but life-saving.


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