Low Butyrylcholinesterase Activity in Dogs Signals Inflammation but Trails CRP as a Biomarker

Butyrylcholinesterase, an enzyme long regarded as biologically enigmatic, has now been examined in one of the largest canine clinical studies to date. Researchers at the University of Bern analyzed plasma BChE activity in 950 client-owned dogs admitted to a university teaching hospital, asking whether the enzyme behaves in dogs as it does in people, where low activity has been linked to obesity, pancreatitis, inflammation, sepsis, and malignancy, often with negative prognostic value. The findings, published in the Journal of Veterinary Internal Medicine, confirm that BChE acts as a negative inflammatory marker in dogs, but they also show that its diagnostic power falls short of C-reactive protein, the established benchmark for systemic inflammation.

BChE is synthesized predominantly by the liver and circulates abundantly in plasma, where its catalytic capacity to hydrolyze esters contributes to cholinergic transmission, the cholinergic anti-inflammatory pathway, and the metabolism of drugs and toxins. In humans, the enzyme participates in lipid and ghrelin metabolism, correlates positively with body mass index, waist circumference, cholesterol, and triglycerides, and declines in severity and mortality in conditions such as acute pancreatitis, SIRS, and sepsis. In dogs, prior evidence was sparse and contradictory: small studies in parvovirosis, ehrlichiosis, demodicosis, and leishmaniasis reported high, low, or normal activities, while an experimental endotoxemia model showed decreased BChE after lipopolysaccharide injection.

The Bern team conducted a retrospective cross-sectional study using the laboratory database of the Small Animal Clinic, Vetsuisse Faculty. They included dogs of any diagnosis for which BChE was measured in lithium-heparin plasma within 24 hours of admission, excluding cases of organophosphate or carbamate intoxication, suspected intoxication with unknown substances, and owners residing abroad. BChE was quantified with a commercial butyrylthiocholine substrate reagent on a Cobas c501 biochemistry analyzer, interpreted against a reference interval of 2749 to 8527 U/L. Additional data included white blood cell count, hematocrit, band neutrophil percentages, and multiple biochemical analytes, alongside signalment, vital signs, diagnoses, and survival outcomes.

The study population was broad and diverse. Median age at presentation was 7.4 years, ranging from 1.5 weeks to 17 years, with 510 of 945 sex-recorded dogs male and 435 female. Mixed breeds, French Bulldogs, Labrador Retrievers, and Chihuahuas were the most frequent breeds among 144 represented. Gastrointestinal disease was the most common primary disorder category, followed by other disorders, neurologic or behavioral conditions, neoplastic diseases, and urogenital disorders. Among dogs with classifiable data, 242 of 770 (31.4%) met criteria for SIRS at admission and 73 of 929 (7.9%) were considered septic.

Admission BChE activities ranged from 482 to 17,348 U/L, with a median of 4553 U/L and an interquartile range of 3485 to 5926 U/L. Only 83 of 950 dogs (8.7%) had activity below the reference interval at admission, 807 (84.9%) were within it, and 60 (6.3%) exceeded it. Disease category was significantly associated with low BChE activity: dogs with immune-mediated and gastrointestinal disorders had significantly lower activity than dogs with neurologic disorders, a difference driven primarily by the very low proportion of neurologic cases with low BChE, likely reflecting fewer cases of systemic inflammation in that group.

Dogs with SIRS and with sepsis had significantly lower admission BChE activity than dogs without these conditions. In univariable logistic regression, each 1000 U/L decrease in BChE was associated with 1.14-fold higher odds of SIRS and 1.24-fold higher odds of sepsis. Dogs with low BChE activity had 2.12-fold higher crude odds of SIRS and 3.42-fold higher crude odds of sepsis compared with dogs without low activity. However, discriminatory ability was limited, with ROC area under the curve values of 0.59 for SIRS and 0.63 for sepsis, indicating substantial overlap in BChE activity between affected and unaffected dogs.

Diagnostic performance analysis revealed that BChE was substantially inferior to CRP for identifying both conditions. CRP achieved ROC AUCs of 0.78 for SIRS and 0.89 for sepsis, compared with 0.59 and 0.63 for BChE. Precision-recall analysis likewise showed poor classification performance for BChE, with low PR-AUC values and low F1 scores. Combining CRP and BChE produced only a statistically significant but clinically minimal improvement for SIRS and no improvement for sepsis, confirming that BChE adds little diagnostic value beyond CRP in dogs.

No significant associations were found between admission BChE activity and obesity, acute pancreatitis, or malignancy, though interpretation was constrained by small numbers of obese and pancreatitis cases and incomplete classification of obesity and neoplastic diseases. The authors caution that grouping all tumors together may have masked disease-specific associations, such as the low BChE previously reported in dogs with high-grade mammary carcinoma. Multivariable analysis identified three independent laboratory predictors of low BChE activity: lower hematocrit, increased band neutrophil percentage, and lower cholesterol concentration, findings consistent with inflammatory and systemic disease processes.

Regarding outcome, low admission BChE activity was associated with slightly prolonged hospitalization and increased crude odds of non-survival to discharge (2.17-fold) and at 3 weeks (2.99-fold). However, in multivariable models adjusting for age, SIRS status, hematocrit, cholesterol, creatinine, bilirubin, and band neutrophil percentage, low admission BChE was not independently associated with mortality. Exploratory serial measurements in 207 dogs suggested that at least one low repeat BChE result during hospitalization was more common (25.6%) than low admission activity and was associated with worse survival, though the retrospective, non-standardized nature of repeat sampling and potential effects of fluid therapy warrant cautious interpretation.

The study concludes that BChE activity reflects systemic inflammation and illness severity in hospitalized dogs but has limited utility as a standalone diagnostic or prognostic biomarker compared with established inflammatory markers such as CRP. The authors note limitations including incomplete classification of SIRS, sepsis, and other categories, the absence of consensus definitions for these conditions, and the possibility that critically ill dogs were sampled and documented more extensively than stable patients. Nonetheless, the large and diverse population strengthens the conclusion that BChE behaves as a negative inflammatory marker in dogs, mirroring findings in human medicine while underscoring the enzyme’s continued diagnostic inferiority to CRP in clinical practice.

Subject of Research: Butyrylcholinesterase activity as an inflammatory and prognostic biomarker in dogs

Article Title: Low plasma butyrylcholinesterase activity in dogs: prevalence, association with underlying disorders, laboratory variables, and survival

Article References: Tesseraux, A. M., Howard, J., & Peters, L. M. (2026). Low plasma butyrylcholinesterase activity in dogs: prevalence, association with underlying disorders, laboratory variables, and survival. Journal of Veterinary Internal Medicine, 40(5), Article aalag237. https://doi.org/10.1093/jvimsj/aalag237

Image Credits: AI Generated

DOI: 10.1093/jvimsj/aalag237

Keywords: butyrylcholinesterase, dogs, SIRS, sepsis, C-reactive protein, veterinary medicine, biomarker, inflammation, plasma, activity, prevalence, association