Biological Variability of C-Reactive Protein and Specific Canine Pancreatic Lipase Immunoreactivity in Apparently Healthy Dogs

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97330, USA.
Journal of Veterinary Internal Medicine (Impact Factor: 1.88). 05/2011; 25(4):825-30. DOI: 10.1111/j.1939-1676.2011.0729.x
Source: PubMed


C-reactive protein (CRP) and specific canine pancreatic lipase immunoreactivity (Spec cPL) are biomarkers of generalized or nonspecific inflammation and pancreatic inflammation in dogs, respectively. The extent of inter- and intraindividual variation over time of these analytes is not well defined in dogs. The minimal critical difference for sequential determinations of these markers (ie, the smallest change necessary to represent physiological change rather than biological variation), has not been defined.
To determine the inter- and intraindividual variability (CV(G) and CV(I) ) and minimal critical difference for sequential determinations of serum CRP and Spec cPL concentrations in apparently healthy dogs.
Eleven apparently healthy dogs owned by staff or students at a veterinary teaching hospital.
Blood was collected repeatedly at varying intervals over 12 weeks. CRP and Spec cPL concentrations were determined with commercially available assays. Indices of inter-, intraindividual, and assay variability and 1-sided minimal critical differences for sequential concentrations were calculated.
For CRP, CV(G) was 90.8%, CV(I) was 115.5%, and the analytical variability (CV(A) ) was 6.3%; the index of individuality was 0.74, and 1-sided critical difference was 269.9%. For Spec cPL, CV(G) = 49.48%, CV(I) = 193.8%, CV(A) = 8.4%, index of individuality = 0.24, and 1-sided critical difference was 452.6%.
A population-based reference range is appropriate for Spec cPL, but questionable for CRP in dogs. Large changes in serial measurements of Spec cPL are necessary to infer clinical importance, more modest changes in CRP are likely to be meaningful.

Download full-text


Available from: Craig G Ruaux, Oct 07, 2014
1 Follower
40 Reads
  • Source
    • "Diagnosis of pancreatitis in dogs with babesiosis is hindered by mild to moderate forms of pancreatitis not being associated with clinical signs or by clinical signs overlapping with those of babesiosis; yet even mild or moderate pancreatitis may contribute overall to morbidity and mortality. Carney et al. (2011) proposed that population-specific reference ranges need to be created to improve sensitivity of detecting pancreatitis in dogs with chronic stable disease versus dogs with clinical signs ascribable to severe acute pancreatitis. The specificity of serum cPL concentration, with a cut-off value > 400 µg/L, was 97.5% (Neilson-Carley et al. 2011; Newman et al. 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Babesia rossi is the cause of a highly virulent multisystemic disease with a variable outcome, which is a reliable model of systemic inflammatory response syndrome (SIRS). The objective of this study was to determine the concentration of canine pancreatic-specific lipase (cPL) in a population of dogs with naturally acquired B. rossi infection. In addition, the associations between serum cPL and death and SIRS status were examined. An observational study recruited 87 dogs diagnosed with B. rossi infection and serum cPL concentrations were measured daily until discharge or death. The median concentration of serum cPL was 124.0 µg/L (interquartile range: 51.0 µg/L – 475.5 µg/L) on admission (n = 87) and 145.5 µg/L (62.3 µg/L – 434.0 µg/L) on day two of hospitalisation (n = 40). Twenty-four dogs (28%) had a serum cPL concentration within the diagnostic range for pancreatitis (> 400 µg/L) at admission with 13 dogs (32.5%) presenting as such on the second day of hospitalisation. The median concentration of serum cPL in dogs with SIRS was 158 µg/L (interquartile range: 52.5 µg/L – 571.5 µg/L; n = 53), which was significantly higher than in those without SIRS (75 µg/L; 50.3 µg/L – 131.8 µg/L; n = 32) (P = 0.018). This study demonstrated that an unexpectedly high number of dogs diagnosed with naturally acquired canine babesiosis had a serum cPL concentration within the diagnostic range for acute pancreatitis and a significantly higher serum cPL concentration was found in dogs that were classified as having SIRS.
    Journal of the South African Veterinary Association 03/2015; 86(1). DOI:10.4102/jsava.v86i1.1297 · 0.35 Impact Factor
  • Journal of Veterinary Internal Medicine 26(1):1; author reply 2. DOI:10.1111/j.1939-1676.2011.00857.x · 1.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: S100A12 (calgranulin C) is a Ca(2+)-binding protein that has been proposed to play a central role in both innate and acquired immune responses. In humans, S100A12 has been reported to be increased in serum and/or plasma in patients with various inflammatory disorders, and this protein has been suggested to be a sensitive and specific marker for inflammatory bowel disease (IBD). An immunoassay for S100A12 is currently available for use in humans, but antibodies against the human protein do not cross-react with canine S100A12 (cS100A12). Both sensitive and specific markers for canine patients with systemic or localized inflammatory diseases are currently lacking, thus the aim of this study was to develop and analytically validate a radioimmunoassay (RIA) for the quantification of cS100A12 in serum and fecal specimens and to determine the biological variation of cS100A12 in serum from healthy dogs. A competitive liquid-phase RIA was developed and analytically validated by determining assay working range, dilutional parallelism, spiking recovery, and intra- and inter-assay variability. Reference intervals for serum and fecal concentrations of cS100A12 were established from 124 and 65 healthy dogs, respectively, and components of variation for serum cS100A12 were determined from 11 dogs over 2.6 months. The working range of the assay was 0.6-432.7 μg/L. No cross-reactivity was observed with the cS100A8/A9 protein complex, the closest structural analogues available. Observed-to-expected ratios (O/E) for the serial dilution of serum and fecal extracts ranged from 97.2 to 146.8% and from 75.3 to 129.8%, respectively. O/E for spiking recovery for serum and fecal extracts ranged from 87.8 to 130.4% and from 84.8 to 143.8%, respectively. Coefficients of variation (CV) for intra- and inter-assay variability for sera were ≤ 8.1% and ≤ 7.8%, respectively, and were ≤ 7.8% and ≤ 8.7%, respectively, for fecal extracts. Reference intervals for serum and fecal cS100A12 were 33.2-225.1 μg/L and <24-745 ng/g, respectively. For biological variability testing, analytical, intra-individual, inter-individual, and total CV were 5.7, 29.2, 31.2, and 66.0%, respectively, yielding an index of individuality of 0.95 and a minimum critical difference (p<0.05) for sequential values of 84.9%. The RIA for cS100A12 measurement described here is analytically sensitive and specific, linear, accurate, precise, and reproducible, and will facilitate further research into the clinical utility of quantifying serum and fecal cS100A12 in canine patients with inflammatory diseases. Moderate changes in serum cS100A12 concentrations may be clinically relevant; however, the use of a population-based reference interval may require caution.
    Veterinary Immunology and Immunopathology 12/2011; 144(3-4):200-9. DOI:10.1016/j.vetimm.2011.09.011 · 1.54 Impact Factor
Show more