“Stinger”, a dog with sepsis from a bite wound. Image from Valley Center Veterinary Clinic, Valley Center, CA.

N-terminal portion of pro C-type natriuretic peptide. Try to say that one three times fast. ScienceDaily has a cool article detailing a couple new studies showing that this peptide (Nt-pCNP) could be a solid indicator of sepsis as opposed to a generalized inflammatory response. It could potentially be added to current serum chemistry analysis, or packaged as an ELISA snap for quick, in-house diagnostics for pertinent cases.

Overuse of antibiotics has been a long term problem that is being well addressed in human medicine, however they are used much more broadly and liberally in animals due to their non-prescription access (especially in large animal work), and their use as a diagnostic tool for patients who can’t speak and often can’t afford thorough diagnostics. A veterinarian who’s client is unwilling to pay for a culture will often send broad spectrum antibiotics home anyway as a less expensive option in the hopes that they will take care of the problem.

I was unable to find a chemistry profile of Nt-pCNP, but the journal article itself talks a bit about C-type natriuretic peptide. CNP is produced by vascular endothelial cells and immune system macrophages. It “inhibits microbial growth and modifies pathogenicity of microorganisms” (DeClue, 2011). The problem with looking for just CNP as an indicator of sepsis is that it has a very short half life, and tends to degrade even faster in removed serum. Therefore, the researchers decided to use Nt-pCNP as their target molecule.  Nt-pCNP is created in a 1:1 ratio with CNP as a byproduct, and is much more durable and long-lived in both the bloodstream and collected serum.

The results of the study support the hypothesis  that CNP is a good indicator of sepsis, however like anything else, it’s not ideal. CNP was shown to be a poor indicator of sepsis when the infection was peritoneal. This includes gastrointestinal perforations or other possible infections found within the peritoneum (the authors mention that using peritoneal fluid as opposed to serum from a distal point may yield better sensitivity). Taking these false negatives into account, the test had a 65.5% sensitivity, for all other origins of sepsis in the study, sensitivity was 92%. Unfortunately, there appears to be a large potential for ambiguous negatives when peritoneal infection is suspected, but it’s always important to remember to educate clients that medicine is rarely black and white. It’s nice that House is able to identify exactly what’s wrong with each of his patients every week, but most of the time, we’re just going to give them supportive care based on the most likely result. Some of the limitations of the study that the authors mentioned were the small sample size and uncontrolled natures of the ailments that may have influenced the blood chemistry (samples taken from bacterial vs. viral infections, condition as of admission, underlying secondary infection or ailment, etc.).

In the case of this test and many other lab tests, positives are very definitive and help us out, while negatives are ambiguous. This is true whether it’s a heartworm test, fine needle aspirate, fecal flotation, radiology, or any number of other diagnostic tests. Every one is a tool, and hopefully looking at Nt-pCNP levels will give us another way to confirm sepsis while our cultures are growing at the lab, or perhaps offering another faster or less expensive option that the situation necessitates.
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DeClue AE, Osterbur K, Bigio A, & Sharp CR (2011). Evaluation of serum NT-pCNP as a diagnostic and prognostic biomarker for sepsis in dogs. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, 25 (3), 453-9 PMID: 21457321