Neutrophil gelatinase-associated lipocalin in dogs with chronic kidney disease, carcinoma, lymphoma and endotoxaemia.

OBJECTIVES: To measure serum and urine neutrophil gelatinase-associated lipocalin (NGAL) concentrations in healthy dogs and dogs with chronic kidney disease, neoplasia and endotoxaemia. METHODS: Serum and urine NGAL concentrations were measured in 42 healthy dogs, 11 dogs with chronic kidney disease, 12 dogs with carcinoma, 20 dogs with lymphoma and 15 dogs with lipopolysaccharide-induced endotoxaemia. In dogs with chronic kidney disease, NGAL was measured 3 and 6 months later. RESULTS: Compared with healthy controls, dogs with chronic kidney disease (PÄ0·0008), carcinoma (PÄ0·0072) and lymphoma (PÄ0·0008) had elevated serum and urine NGAL and urine NGAL-to-creatinine ratio. Serum and urine NGAL was not significantly different between dogs with chronic kidney disease, carcinoma or lymphoma (Pê0·12). In dogs with non-progressive chronic kidney disease, NGAL concentrations did not change significantly over the 6-month study period. CLINICAL SIGNIFICANCE: NGAL can be elevated by chronic kidney disease and neoplasia, compared with healthy controls. Further research is needed to determine if uNGAL or uNGAL-to-creatinine ratio is more specific than serum levels to detect chronic kidney disease.

Serial Evaluation of Abdominal Fluid and Serum Amino-terminal pro-C-type Natriuretic Peptide in Dogs with Septic Peritonitis.

BACKGROUND: Serum N-terminal pro-C-natriuretic peptide (NT-proCNP) has shown promise as a diagnostic biomarker for sepsis. Its sensitivity to detect dogs with septic peritonitis (SP) is reportedly low, perhaps attributable to the compartmentalization of NT-proCNP in the abdominal cavity. OBJECTIVES: To evaluate the use of an ELISA for the measurement of NT-proCNP in canine abdominal fluid and to describe the peri-operative pattern of abdominal fluid and serum NT-proCNP concentrations in dogs with SP. ANIMALS: Five client-owned dogs with nonseptic abdominal effusion of varying etiologies and 12 client-owned dogs with SP undergoing abdominal surgery and placement of a closed-suction abdominal drain (CSAD). Six dogs were included upon hospital admission; 6 were included the day after surgery. METHODS: Prospective pilot study. A commercially available ELISA kit was analytically validated for use on canine abdominal fluid. The NT-proCNP concentrations were measured in the abdominal fluid of control dogs, and in serum and abdominal fluid of dogs with SP from admission for CSAD removal. RESULTS: In dogs with SP, admission abdominal fluid NT-proCNP concentrations were lower than the concurrent serum concentrations (P = 0.031), and lower than control canine abdominal fluid concentrations (P = 0.015). Postoperatively, abdominal fluid NT-proCNP concentrations remained lower than serum concentrations (P < 0.050), except on day 4. CONCLUSIONS AND CLINICAL IMPORTANCE: The ELISA kit was able to measure NT-proCNP in canine abdominal fluid. In dogs with SP, low serum NT-proCNP concentrations cannot be explained by abdominal compartmentalization.

Effect of synthetic colloid administration on coagulation in healthy dogs and dogs with systemic inflammation.

BACKGROUND: Synthetic colloids are often used during fluid resuscitation and affect coagulation. OBJECTIVE: To compare the effects of an isotonic crystalloid and synthetic colloid on coagulation in healthy dogs and dogs with systemic inflammation. ANIMALS: Sixteen adult purpose-bred Beagles. METHODS: Randomized, placebo-controlled, blinded study. Dogs were randomized into one of two groups receiving fluid resuscitation with either 40 mL/kg IV 0.9% NaCl or tetrastarch after administration of lipopolysaccharide or an equal volume of placebo. After a 14-day washout period, the study was repeated such that dogs received the opposite treatment (LPS or placebo) but the same resuscitation fluid. Blood samples were collected at 0, 1, 2, 4, and 24 hours for measurement of coagulation variables. RESULTS: Administration of either fluid to healthy dogs and dogs with systemic inflammation resulted in similar increases in prothrombin time and activated clotting time. In comparison to saline administration, tetrastarch administration resulted in significantly decreased R (P = .017) in healthy dogs, as well as significantly increased activated partial thromboplastin time (P ≤ .016), CL30% (P ≤ .016), and K (P < .001) and significantly decreased platelet count (P = .019), α (P ≤ .001), MA (P < .001), and von Willebrand factor antigen (P < .001) and collagen binding activity (P ≤ .003) in both healthy dogs and dogs with systemic inflammation. CONCLUSIONS AND CLINICAL IMPORTANCE: Tetrastarch bolus administration to dogs with systemic inflammation resulted in a transient hypocoagulability characterized by a prolonged activated partial thromboplastin time, decreased clot formation speed and clot strength, and acquired type 1 von Willebrand disease.

N-terminal pro-C-natriuretic peptide and cytokine kinetics in dogs with endotoxemia.

BACKGROUND: Serum N-terminal pro-C-natriuretic peptide (NT-proCNP) concentration at hospital admission has sufficient sensitivity and specificity to differentiate naturally occurring sepsis from nonseptic systemic inflammatory response syndrome (SIRS). However, little is known about serum NT-proCNP concentrations in dogs during the course of sepsis. OBJECTIVE: To determine serum NT-proCNP and cytokine kinetics in dogs with endotoxemia, a model of canine sepsis. SAMPLES: Eighty canine serum samples. METHODS: Eight healthy adult Beagles were randomized to receive Escherichia coli lipopolysaccharide (LPS, 5 µg/kg) or placebo (0.9% NaCl) as a single IV dose in a randomized crossover study. Serum collected at 0, 1, 2, 4, and 24 hours was stored at -80°C for batch analysis. Serum NT-proCNP was measured by ELISA and 13 cytokines and chemokines by multiplex magnetic bead-based assay. RESULTS: Serum NT-proCNP concentrations did not differ significantly between LPS- and placebo-treated dogs at any time. When comparing serum cytokine concentrations, LPS-treated dogs had higher interleukin-6 (IL-6), IL-10, TNF-α and KC-like at 1, 2, and 4 hours; higher CCL2 at 1, 2, 4, and 24 hours; and higher IL-8 and CXCL10 at 4 hours compared to placebo-treated dogs. There were no differences in serum GM-CSF, IFN-γ, IL-2, IL-7, IL-15 or IL-18 between LPS- and placebo-treated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum NT-proCNP concentration does not change significantly in response to LPS administration in healthy dogs. Certain serum cytokine and chemokine concentrations are significantly increased within 1-4 hours after LPS administration and warrant further investigation as tools for the detection and management of sepsis in dogs.

Investigation of a commercial ELISA for the detection of canine procalcitonin.

BACKGROUND: Rapid identification of sepsis enables prompt administration of antibiotics and is essential to improve patient survival. Procalcitonin (PCT) is a biomarker used to diagnose sepsis in people. Commercial assays to measure canine PCT peptide have not been validated. OBJECTIVE: To investigate the validity of a commercially available enzyme-linked immunosorbent assay (ELISA) marketed for the measurement of canine PCT. ANIMALS: Three dogs with sepsis, 1 healthy dog, 1 dog with thyroid carcinoma. METHODS: Experimental study. The ELISA's ability to detect recombinant and native canine PCT was investigated and intra-assay and interassay coefficients of variability were calculated. Assay validation including mass spectrometry of the kit standard solution was performed. RESULTS: The ELISA did not consistently detect recombinant canine PCT. Thyroid lysate yielded a positive ELISA signal. Intra-assay variability ranged from 18.9 to 77.4%, while interassay variability ranged from 56.1 to 79.5%. Mass spectrometry of the standard solution provided with the evaluated ELISA kit did not indicate presence of PCT. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this investigation do not support the use of this ELISA for the detection of PCT in dogs.

Hypocalcemia and hypovitaminosis D in dogs with induced endotoxemia.

BACKGROUND: Hypocalcemia is a documented electrolyte disturbance in people and animals with sepsis, but its mechanism is poorly understood. OBJECTIVE: To investigate mechanisms of hypocalcemia in dogs with experimentally induced endotoxemia. ANIMALS: Six healthy mixed breed dogs were included in this nonrandomized, placebo-controlled, crossover study. METHODS: Dogs initially were injected with placebo (0.9% NaCl; 1 mL, IV) and then lipopolysaccharide (LPS; 2 µg/kg, IV) after a 5-day washout period. Blood and urine samples were collected for measurement of serum total calcium (tCa), ionized calcium (iCa), total magnesium (tMg), ionized magnesium (iMg), parathyroid hormone (PTH), 25-hydroxyvitamin D (vitamin D), venous blood gases, and fractional excretion (FE) of calcium. RESULTS: After LPS administration, body temperature increased and blood pressure decreased. Both iCa and tCa decreased (P < .01), but iMg was not significantly different between control and LPS treatments. PTH concentrations increased (P < .01) and vitamin D concentrations decreased (P < .01). Venous pH, bicarbonate, base excess, and blood glucose also decreased (P < .01). Urine tCa concentration was below the limit of detection for all dogs after LPS administration. CONCLUSIONS: Hypocalcemia occurs during endotoxemia in dogs and is associated with hypovitaminosis D. Hypomagnesemia, hypoparathyroidism, alkalosis, and increased calciuresis are not associated with hypocalcemia in endotoxemic dogs.

Babesiosis caused by a large Babesia species in 7 immunocompromised dogs.

BACKGROUND: A large unnamed Babesia species was detected in a dog with lymphoma. It was unknown if this was an underrecognized pathogen. OBJECTIVE: Report the historical and clinicopathologic findings in 7 dogs with babesiosis caused by a large unnamed Babesia species characterize the 18S ribosomal ribonucleic acid (rRNA) genes. ANIMALS: Seven immunocompromised dogs from which the Babesia was isolated. METHODS: Retrospective case review. Cases were identified by a diagnostic laboratory, the attending clinicians were contacted and the medical records were reviewed. The Babesia sp. 18S rRNA genes were amplified and sequenced. RESULTS: Six of 7 dogs had been splenectomized; the remaining dog was receiving oncolytic drugs. Lethargy, anorexia, fever, and pigmenturia were reported in 6/7, 6/7, 4/7, and 3/7 dogs. Laboratory findings included mild anemia (7/7) and severe thrombocytopenia (6/7). Polymerase chain reaction (PCR) assays used to detect Babesia sensu stricto species were all positive, but specific PCR assays for Babesia canis and Babesia gibsoni were negative in all dogs. The 18S rRNA gene sequences were determined to be identical to a large unnamed Babesia sp. previously isolated. Cross-reactive antibodies against other Babesia spp. were not always detectable. Five dogs were treated with imidocarb dipropionate and 1 dog with atovaquone/azithromycin; some favorable responses were noted. The remaining dog was untreated and remained a clinically stable carrier. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with pigmenturia, anemia, and thrombocytopenia should be tested for Babesia sp. by PCR. Serology is not sufficient for diagnosis of this Babesia sp. Asplenia, chemotherapy, or both might represent risk factors for persistent infection, illness, or both.

Ionized hypocalcemia in critically ill dogs.

BACKGROUND: Ionized hypocalcemia (iHCa) is a common electrolyte disturbance in critically ill people, especially those with sepsis. The cause of the iHCa is not entirely understood and is likely multifactorial. Critically ill people with iHCa have longer hospital stays and higher mortality rates compared to people with normocalcemia. There are no published clinical studies evaluating the incidence and impact of iHCa in critically ill dogs. HYPOTHESIS: iHCa occurs in critically ill dogs, is more prevalent in dogs with systemic inflammatory response syndrome (SIRS) or sepsis, and is associated with longer hospital stays and higher mortality. ANIMALS: One hundred and forty-one client-owned dogs admitted to a companion animal intensive care unit (ICU) in a veterinary teaching hospital. METHODS: Prospective observational study of sequentially enrolled dogs. Blood was collected and analyzed within an hour of admission from all dogs presented to the ICU that met study inclusion criteria. RESULTS: The incidence of iHCa (iCa < 1.11 mmol/L) was 16%. The presence of iHCa was associated with longer ICU (P= .038) and hospital (P= .012) stays but not with decreased survival (P= .60). Dogs with sepsis as defined by >or=3 SIRS criteria and a positive culture were more likely to have iHCa (P= .050). CONCLUSIONS AND CLINICAL RELEVANCE: In dogs not previously treated with fluids or blood products intravenously, the finding of iHCa upon admission to the ICU predicted a longer duration of ICU and hospital stay. Septic dogs with positive cultures were more likely to have iHCa.