Diagnosis of Pancreas Allograft Rejection?

Robert J. Stratta, MD

Disclosures

November 15, 2001

Question

Is there a believable laboratory exam for rejection of the transplanted pancreas?

A.I. David, MD

Response from Robert J. Stratta, MD

At present, the only consistently reliable method of diagnosing acute rejection of the pancreas allograft is biopsy (either percutaneous, transcystoscopic if bladder-drained, or open). Serologic markers of rejection can be characterized as:

  • endocrine (glucose, insulin, C-peptide, glucagon, glucose disappearance, proinsulin, pancreatic polypeptide, provocative or stimulation tests)

  • exocrine (amylase, lipase, immunoreactive anodal trypsin, pancreas-specific protein, secretory trypsin inhibitor, pancreatitis specific protein)

  • immune (beta-2-microglobulin, interleukin [IL]-2 receptor, neopterin, C-reactive protein, tumor necrosis factor, IL-6, adhesion molecules, perforin, granzyme B, thromboxane B2, prostaglandin E2, platelet-activating factor, Fas ligand, HLA antigens).

Pancreas rejection can be characterized as subclinical, occult, or subtle, which makes the diagnosis elusive. In general, the exocrine pancreas rejects before the endocrine pancreas (both clinically and histologically), so exocrine markers appear to change prior to alterations in glucose control. Hyperglycemia tends to occur late in the rejection process due to the tremendous islet cell reserve and may portend a poor prognosis. There is also a hierarchy of rejection, with the frequency and severity of rejection greater in pancreas alone, greater than pancreas after kidney, greater than simultaneous pancreas-kidney transplant (SPKT) recipients. Although the pancreas allograft is more susceptible to acute rejection, it is less susceptible to chronic rejection, particularly in SPKT recipients. In SPKT recipients, the incidence (and manifestations) of renal allograft rejection usually occur earlier than pancreas allograft rejection. Consequently, the serum creatinine is a good surrogate marker for rejection in SPKT recipients. However, pancreas allograft rejection is usually rapid, unpredictable, and steroid-resistant, and may occur discordant to the kidney. Finally, differentiating immune-mediated pancreatitis (rejection) from nonimmune-mediated causes (cytomegalovirus, ischemia, reperfusion injury, infection) may be difficult.

In patients with bladder drainage, urine amylase determinations are helpful (as is urine cytology monitoring). However, both of these parameters (50% or greater reduction in timed urine amylase on 2 consecutive samples 24 hours apart or positive urine cytology) have false-positives and lack sensitivity and specificity.

From my own experience, I find the serum lipase level to be the most useful marker because it is pancreas-specific, relatively sensitive and specific, inexpensive, easy to perform (rapid turnaround time), and available at most labs. An elevation in the serum lipase level usually results in imaging studies and subsequent biopsy of the transplanted pancreas in order to confirm the diagnosis.

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