In a patient with a history of type 1 or type 2 diabetes or chronic pancreatitis, and potential comorbidities such as hypertension, hyperlipidemia, or kidney disease, who is suspected of having a pancreatic transplant rejection, should both amylase and lipase be ordered, and if glucose is elevated, should C-peptide also be ordered?

Monitoring for Pancreatic Transplant Rejection

In suspected pancreatic transplant rejection, order both amylase and lipase together, as lipase is more specific for pancreatic injury (with 99.8% negative predictive value) while amylase can be elevated in non-pancreatic conditions, and when elevated glucose is present, C-peptide should be ordered to assess endocrine graft function. 1, 2

Laboratory Monitoring Strategy

Pancreatic Enzyme Testing

Order both amylase and lipase simultaneously for the following reasons:

• Lipase is more reliable and specific for pancreatic injury than amylase, with higher sensitivity (79% vs 72%) and a larger diagnostic window (remains elevated 8-14 days vs 3-7 days for amylase) 1
• When used together with ultrasonography, the combination achieves 88% sensitivity and 96% negative predictive value for pancreatic pathology 1
• Amylase can be falsely elevated in non-pancreatic conditions including renal disease (common in transplant recipients), bowel obstruction, and after hypoperfusion 1
• In transplant recipients with chronic kidney disease or concurrent kidney transplants, amylase is frequently elevated without pancreatitis, though levels >3 times upper limit of normal suggest true pancreatic pathology 3

Key monitoring parameters for rejection:

• Elevations >3 times the upper limit of normal for either enzyme warrant immediate evaluation 1
• Monitor both kidney and pancreas function together, as 35% of rejection episodes involve kidney alone while 12% involve both organs 4
• Serial measurements starting 3-6 hours after suspected rejection can support clinical evaluation 1

C-Peptide Testing with Elevated Glucose

Order C-peptide when glucose is elevated because:

• Hyperglycemia may indicate severe acute rejection and has been specifically associated with antibody-mediated rejection in pancreas transplants 2
• C-peptide assessment is critical for diagnosing antibody-mediated rejection and determining endocrine graft function, as preserved C-peptide despite elevated glucose can occur even with severe rejection 2
• The correlation between pancreas allograft biopsy, C4d staining, donor-specific antibodies, and C-peptide levels is essential to diagnose antibody-mediated rejection and initiate correct treatment 2

Clinical Context and Pitfalls

Important caveats:

• Preserved endocrine function (normal glucose and C-peptide) can occur despite severe acute cellular and antibody-mediated rejection, so normal glucose does not exclude rejection 2
• The degree of enzyme elevation does not correlate with rejection severity—patients with slight elevations can have severe rejection 1
• In patients with concurrent kidney transplants or chronic kidney disease, interpret amylase cautiously as it is frequently elevated without pancreatic pathology 3
• Allograft biopsy remains the gold standard when dysfunction is noted, as it can distinguish rejection from non-immunologic causes (donor disease, ischemic injury, vascular thrombosis, pancreatitis, recurrent diabetes) 5

Monitoring frequency:

• Close monitoring of blood glucose during the first month and every 3 months for the first year is recommended 6
• Serial clinical examinations are more important than trending enzyme levels for assessing disease progression 1
• Persistently elevated enzymes after 10 days warrant monitoring for complications such as pseudocyst formation 1