Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies

Abstract

BackgroundCalprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown.ObjectiveEvaluation of fecal calprotectin in dogs with biopsy‐confirmed CIE.Animals127 dogs.MethodsProspective case‐control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C‐reactive protein (CRP) were measured. Food‐ or antibiotic‐responsive cases (FRE/ARE, n = 13) were distinguished from steroid‐/immunosuppressant‐responsive or ‐refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR).ResultsFecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%‐100%) and 75% specificity (95%CI: 43%‐95%).Conclusions and Clinical ImportanceFecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment.

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

“…Hypofolatemia can result from chronic malabsorption in the proximal small intestine and was detected in 14% of dogs with CIE in 1 study,50 but a decreased serum folate concentration is not specific for CIE and normofolatemia does not exclude a diagnosis of CIE. Serum folate concentration can be falsely normal or increased because of secondary small intestinal dysbiosis (with increased folate production by some members of the intestinal microbiota) or hypocobalaminemia and should be monitored after cobalamin supplementation 55. Oral folic acid supplementation (10 μg/kg or 200‐400 μg/dog PO q24h for 30 days) is recommended in patients with moderate or marked hypofolatemia.…”

“…Calprotectin is a stable protein complex that can be extracted and measured in fecal samples 50, 119, 120. Fecal calprotectin concentrations have been evaluated in dogs with chronic gastrointestinal inflammation50, 95, 121 and appear to serve as a useful biomarker of intestinal inflammation in dogs.…”

“…Fecal calprotectin concentrations have been evaluated in dogs with chronic gastrointestinal inflammation50, 95, 121 and appear to serve as a useful biomarker of intestinal inflammation in dogs. Fecal calprotectin concentrations are a good surrogate marker of disease severity in dogs with CIE,50, 95, 121 with a cut‐off value of ~50 μg/g feces to identify dogs with severe clinical disease 121.…”

“…Fecal calprotectin concentrations have been evaluated in dogs with chronic gastrointestinal inflammation50, 95, 121 and appear to serve as a useful biomarker of intestinal inflammation in dogs. Fecal calprotectin concentrations are a good surrogate marker of disease severity in dogs with CIE,50, 95, 121 with a cut‐off value of ~50 μg/g feces to identify dogs with severe clinical disease 121. Fecal calprotectin concentration also appears to have utility in predicting the response to treatment in dogs with CIE,50 and concentrations ≥15.2 μg/g distinguish partial responders or nonresponders (PR/NR) from dogs with IRE that achieve complete clinical remission (CR) with a sensitivity of 80% and a specificity of 75%.…”

“…Fecal calprotectin concentrations are a good surrogate marker of disease severity in dogs with CIE,50, 95, 121 with a cut‐off value of ~50 μg/g feces to identify dogs with severe clinical disease 121. Fecal calprotectin concentration also appears to have utility in predicting the response to treatment in dogs with CIE,50 and concentrations ≥15.2 μg/g distinguish partial responders or nonresponders (PR/NR) from dogs with IRE that achieve complete clinical remission (CR) with a sensitivity of 80% and a specificity of 75%. Given the 45% prevalence of PR/NR in that study, PPV (77%) and NPV (82%) for fecal calprotectin to identify PR/NR are fairly high.…”