Understanding lipase assays in the diagnosis of pancreatitis in veterinary medicine

Abstract

Pancreatitis commonly occurs in humans, dogs, and cats. For both veterinary and human health-care professionals, measurement of serum pancreatic lipase concentration or activity provides useful support for a diagnosis of pancreatitis. In this Currents in One Health manuscript, we will discuss commonly used lipase assays in veterinary medicine, namely catalytic colorimetric and immunological lipase assays. We highlight potential diagnostic pitfalls associated with analytical specificity, assay validation, and sample condition interferences. Catalytic lipase assays may detect extrapancreatic lipases. In addition, we propose a decision tree for interpretation of lipase assays in the context of a clinical patient.

Analytical validation of an ELISA for the measurement of feline pancreas‐specific lipase and re‐evaluation of the reference interval and decision threshold for diagnosing pancreatitis

“…(2) agreement between different biomarkers is not equivalent to these biomarkers having the same sensitivity and specificity 17 and thus differentiation between health and disease; (3) agreement of a biomarker with a reference standard (eg, ultrasound results or histopathology) might be influenced by the imperfection of the selected reference standard (for example, the result of the reference standard might be affected by differences in disease severity, disease chronicity, and lesion distribution), as early pancreatitis might not be associated with evident morphologic changes. 18 Thus, the poor agreement between a biomarker using selected cutoffs for diagnosing pancreatitis with either ultrasonographic diagnosis of pancreatitis 10 or pancreatic histopathology 11 might reflect that patients had a reduction in the release of enzymes due to a milder form of pancreatitis, which the assay may not be sensitive enough to detect, 6 or a reduction in acinar cell mass in advanced stages of pancreatitis due to pancreatic atrophy and fibrosis.…”

“…Classification and diagnosis algorithms using this logic have been developed for pancreatitis in humans 20,21 and could be useful for pancreatitis in cats, too. Readers are referred to other publications for detailed discussions about lipases 22 and their use for diagnosing pancreatitis in veterinary medicine 17 and to the recent ACVIM consensus statement on pancreatitis in cats. 23 Due to the often mild or vague clinical presentation, and its unknown relevance with respect to commonly found histological changes, 1 the clinical significance of pancreatitis or the detection of increased pancreas-specific lipase in cats might vary from patient to patient.…”

“…Serum lipase activity, as measured by assays using 1,2‐o‐dilauryl‐rac‐glycero‐3‐glutaric acid‐(6′‐methylresorufin) ester (DGGR) as a substrate, has been evaluated for its diagnostic utility in pancreatitis in cats and was shown to have a good agreement with the Spec fPL assay 9,10,15 . However, studies focused on agreement need to be interpreted cautiously for several reasons: (1) DGGR is not a specific substrate for hydrolysis by pancreatic lipase but is also broken down by other enzymes 16 and as a result, lipase of extra‐pancreatic sources could impact the results of the DGGR lipase activity assay; (2) agreement between different biomarkers is not equivalent to these biomarkers having the same sensitivity and specificity 17 and thus differentiation between health and disease; (3) agreement of a biomarker with a reference standard (eg, ultrasound results or histopathology) might be influenced by the imperfection of the selected reference standard (for example, the result of the reference standard might be affected by differences in disease severity, disease chronicity, and lesion distribution), as early pancreatitis might not be associated with evident morphologic changes 18 . Thus, the poor agreement between a biomarker using selected cutoffs for diagnosing pancreatitis with either ultrasonographic diagnosis of pancreatitis 10 or pancreatic histopathology 11 might reflect that patients had a reduction in the release of enzymes due to a milder form of pancreatitis, which the assay may not be sensitive enough to detect, 6 or a reduction in acinar cell mass in advanced stages of pancreatitis due to pancreatic atrophy and fibrosis 19 .…”

“…Classification and diagnosis algorithms using this logic have been developed for pancreatitis in humans 20,21 and could be useful for pancreatitis in cats, too. Readers are referred to other publications for detailed discussions about lipases 22 and their use for diagnosing pancreatitis in veterinary medicine 17 and to the recent ACVIM consensus statement on pancreatitis in cats 23 …”

Partial validation of the Vcheck canine pancreatic lipase assay

“…Measurement of serum or plasma canine pancreatic lipase (cPL), an enzyme that is synthesized in pancreatic acinar cells, is recommended as part of the diagnostic work‐up in dogs with suspected pancreatitis 2,5,6 . A validated canine‐specific cPL ELISA (Spec cPL) is available at referral laboratories, but because acute pancreatitis is a highly dynamic process that can lead to life‐threatening complications quickly, an in‐house cPLI test would be valuable for obtaining rapid test results 2,4,7,8 . The aim of this study was to evaluate a point‐of‐care cPLI test, Vcheck cPL (BioNote, Inc., Hwaseong‐si, Gyeonggi‐do, Republic of Korea), by performing the following studies: (a) precision, (b) linearity under dilution, (c) comparison to a previously validated cPLI ELISA, Spec cPL, and (d) investigating the performance of the assay in a clinical setting by a retrospective clinical study where cPLI concentrations from dogs with and without acute pancreatitis were determined.…”