Serum concentrations of leptin and adiponectin in dogs with chronic kidney disease

BackgroundAn imbalance in adipokines is associated with the progression of chronic kidney disease (CKD) in humans. However, alterations in adipokines in dogs with CKD remain unclear.ObjectivesTo examine whether adipokine concentrations in serum differ between healthy dogs and dogs with CKD and to determine the correlation between serum adipokine concentrations and CKD severity in dogs.AnimalsTwenty dogs with CKD and 10 healthy dogs.MethodsIn this cross‐sectional study, serum concentrations of leptin, adiponectin, interleukin (IL)‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured in healthy dogs and dogs with CKD, which were classified according to the International Renal Interest Society guidelines.ResultsSerum leptin concentrations were positively correlated with systolic arterial blood pressure (r = .41), creatinine concentrations (r = .39), and symmetric dimethylarginine concentrations (r = .73). Serum adiponectin concentrations (median [range]) in CKD dogs with borderline or non‐proteinuric (20.25 [14.9‐45.8] ng/mL) were significantly higher than those in proteinuric CKD dogs (13.95 [6.4‐22.1] ng/mL; P = .01). Serum IL‐6 (median [range]; 43.27 [24.30‐537.30] vs 25.63 [6.83‐61.03] pg/mL; P = .02), IL‐18 (median [range]; 25.98 [11.52‐280.55] vs 10.77 [3.53‐38.45] pg/mL; P = .01), and TNF‐α (median [range]) concentrations (11.44 [8.54‐38.45] vs 6.105 [3.97‐30.68] pg/mL; P = .02) were significantly different between proteinuric and borderline or non‐proteinuric CKD dogs.Conclusions and Clinical Importanceleptin and adiponectin concentrations in serum might be associated with severity of CKD and proteinuria in dogs with CKD, respectively.     

Serum C‐Reactive Protein as a Diagnostic Biomarker in Dogs with Bacterial Respiratory Diseases

Background

C‐reactive protein (CRP) is a major acute‐phase protein in dogs. Serum concentrations are low in healthy animals, but increase rapidly after inflammatory stimuli.

Objective

The aim of the study was to investigate CRP concentrations in various respiratory diseases of dogs and to determine if CRP can be used as a biomarker in the diagnosis of bacterial respiratory diseases.

Animals

A total of 106 privately owned dogs with respiratory diseases (17 with bacterial tracheobronchitis [BTB], 20 with chronic bronchitis [CB], 20 with eosinophilic bronchopneumopathy [EBP], 12 with canine idiopathic pulmonary fibrosis [CIPF], 15 with cardiogenic pulmonary edema [CPE], and 22 with bacterial pneumonia [BP]) and 72 healthy controls.

Methods

The study was conducted as a prospective cross‐sectional observational study. CRP was measured in serum samples. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and selected diagnostic methods such as cytological and microbiological analysis of respiratory samples, echocardiography, and histopathology.

Results

Dogs with BP had significantly higher CRP concentrations (median, 121 mg/L; interquartile range, 68–178 mg/L) than dogs with BTB (23, 15–38, P = .0003), CB (13, 8–14, P < .0001), EBP (5, 5–15, P < .0001), CIPF (17, 10–20, P < .0001), or CPE (19, 13–32, P < .0001) and healthy controls (14, 8–20, P < .0001). Dogs with BTB had significantly higher CRP concentrations than dogs with CB (P = .001) or EBP (P < .0001) and healthy controls (P = .029).

Conclusion and Clinical Importance

These results indicate that CRP has potential for use as an additional biomarker, especially in the diagnostics of BP.     

Simultaneous steroids measurement in dogs with hyperadrenocorticism using a column-switching liquid chromatography-tandem mass spectrometry method

We developed an analytical method using an on-line column-switching liquid chromatography with triple quadrupole mass spectrometry (LC/MS/MS) for quantifying multiple steroids in serum. Using the developed method, we evaluated the serum concentration of nine steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 21-deoxycortisol, deoxycorticosterone, progesterone, 17α-OH-progesterone and aldosterone) in dogs with hyperadrenocorticism (HAC). Serum was mixed with stable isotope internal standards and thereafter purified by the automated column-switching system. The limit of detection ranged 2–16 pg/ml for nine steroids. In the baseline samples, five steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, and 17α-OH-progesterone) were detected in all dogs. The concentrations of cortisone, 11-deoxycortisol, and 17α-OH-progesterone in dogs with HAC (n=19) were significantly higher those in dogs without HAC (n=15, P<0.02). After the adrenocorticotropic hormone stimulation test, six steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 17α-OH-progesterone, and deoxycorticosterone) were above the limit of quantification in all dogs. Cortisol, corticosterone, cortisone, and deoxycorticosterone concentrations of dogs with HAC were significantly higher than those of dogs without HAC (P<0.02). In addition, 11-deoxycortisol and 17α-OH-progesterone concentration was higher in dogs with HAC than in dogs without HAC (P=0.044 and P=0.048, respectively). The on-line column-switching LC/MS/MS would be feasible for measuring multiple steroids in dog serum. The results suggest that cortisone, 11-deoxycortisol, and 17α-OH-progesterone would be related to HAC. Further studies are warranted to assess the clinical feasibility of steroid profile in dogs with HAC.     

Ultra‐long‐acting recombinant insulin for the treatment of diabetes mellitus in dogs

BackgroundFor the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin‐fragment‐crystallizable (Fc) has an ultra‐long plasma half‐life because it recycles through cells, protected from proteolysis.HypothesisGlycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS‐218d) administered subcutaneously once‐weekly.AnimalsFive client‐owned dogs with naturally occurring DM.MethodsProspective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate‐acting insulin q12h were transitioned to once‐weekly injections of a preliminary construct identified as AKS‐218d. The dose of AKS‐218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS‐218d) and during the last week of treatment. Data were compared using nonparametric paired tests.ResultsOnce‐weekly AKS‐218d, compared to baseline twice‐daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [−0.5‐1.1]; P = .6), fructosamine concentration (−75 mmol/L [−215 to +126]; P = .4), or mean IG (+81 mg/dL [−282 to +144]; P = .8). No adverse reactions were reported.ConclusionControl of clinical signs, body weight, and maintenance of glycemia was achieved with this once‐weekly novel insulin construct in 4 of 5 dogs.     

Clinical evaluation of urinary liver-type fatty acid-binding protein for the diagnosis of renal diseases in dogs

Liver-type fatty acid-binding protein (L-FABP) is a biomarker for the early detection of renal diseases in humans. L-FABP is a cytotoxic oxidation product secreted from the proximal tubules under ischemic and oxidative stress conditions. First, L-FABP gene expression in the kidney and liver was evaluated. Next, the urinary L-FABP concentrations in dogs with or without renal diseases were measured using a novel enzyme-linked immunosorbent assay kit. Urinary L-FABP was normalized relative to urinary creatinine (uCre) concentrations (µg/g uCre). Finally, the relationships between urinary L-FABP and renal biomarkers used in canine medicine or serum alanine transaminase (ALT) as an indicator of liver damage were examined. Serum and urine samples from 94 client-owned dogs including 23 dogs with renal diseases and 71 dogs without renal diseases were used for analysis. Relative L-FABP gene expression was confirmed both in the liver and kidney. Dogs with renal diseases had a significantly higher urinary L-FABP than those without, and its predictive cutoff value was 26 µg/g uCre. Urinary L-FABP was significantly correlated with serum creatinine (r=0.4674, P<0.01), urea nitrogen (r=0.4907, P<0.01), urine specific gravity (r=−0.5100, P<0.01), and urine protein/creatinine ratio (r=0.7216, P<0.01), but not with serum ALT. Hence, dogs with a high urinary L-FABP value were more likely to have renal diseases.     

Serum Biomarkers of Clinical and Cytologic Response in Dogs with Idiopathic Immune‐Mediated Polyarthropathy

Background

Immune‐mediated polyarthopathy (IMPA) is common in dogs, and is monitored by serial arthrocenteses.

Hypothesis/Objectives

Plasma C‐reactive protein (CRP), interleukin‐6 (IL‐6), and CXCL8 (interleukin‐8) would serve as noninvasive markers of joint inflammation in IMPA.

Animals

Nine client‐owned dogs with idiopathic IMPA; 6 healthy controls.

Methods

Prospective study. Plasma CRP, IL‐6, and CXCL8 were measured by ELISA at baseline, 2, and 4 weeks during treatment with prednisone at 50 mg/m²/day. Arthrocenteses, the canine brief pain inventory (CBPI), and accelerometry collars were used to assess joint inflammation, lameness, and mobility at all 3 time points.

Results

C‐reactive protein concentrations were higher in IMPA dogs (median 91.1 μg/mL, range 76.7–195.0) compared with controls (median <6.3 μg/mL, <6.3–13.7; P = .0035), and were significantly lower at week 2 (10.6 μg/mL, <6.3–48.8) and week 4 (<6.3 μg/mL, <6.3–24.4; P < .001).C‐reactive protein was correlated with median CBPI scores (r = 0.68; P = .0004), joint cellularity (r = 0.49, P = .011), and mobility by accelerometry (r = −0.42, P = .048). Plasma IL‐6 concentrations were also higher in IMPA dogs (median 45.9 pg/mL), compared with controls (median <15.7 pg/mL; P = .0008). IL‐6 was lower in IMPA dogs by week 4 (<15.7 pg/mL; P = .0099), and was modestly correlated with CBPI scores (r = 0.47, P = .023). CXCL8 did not differ significantly between IMPA and healthy dogs.

Conclusions

Plasma CRP and IL‐6 might be useful surrogate markers of synovial inflammation and disease activity in dogs with IMPA.     

Cardiac Troponin I and T as Prognostic Markers in Cats with Hypertrophic Cardiomyopathy

Background

Myocardial injury detected by cardiac troponin I and T (cTnI and cTnT) in cardiac disease is associated with increased risk of death in humans and dogs.

Hypothesis

Presence of myocardial injury predicts long‐term death in cats with hypertrophic cardiomyopathy (HCM), and ongoing myocardial injury reflects change in left ventricular wall thickness over time.

Animals

Thirty‐six cats with primary HCM.

Methods

Prospective cohort study. Cats with HCM were included consecutively and examined every 6 months. Echocardiography, ECG, blood pressure, and serum cTnI and cTnT were evaluated at each visit. Cox proportional hazards regression analysis was performed to evaluate prognostic potential of serum troponin concentrations at admission and subsequent examinations. Correlations were used to examine associations between troponin concentrations and cardiac hypertrophy.

Results

Troponin concentrations at admission were median [range] 0.14 [0.004–1.02] ng/mL for cTnI, and 13 [13–79.5] ng/L for cTnT. Both were prognostic for death (P = .032 and .026) as were the last available concentrations of each (P = .016 and .003). The final cTnT concentration was a significant predictor of death even when adjusting for the admission concentration (P = .043). In a model containing both markers, only cTnT remained significant (P = .043). Left ventricular free wall thickness at end‐diastole (LVFWd) at admission was correlated with cTnI at admission (r = 0.35, P = .035), however no significant correlations (r = 0.2–0.31, P = .074–.26) were found between changes in troponin concentrations and left ventricular thickness over time.

Conclusions and Clinical Importance

Myocardial injury is part of the pathophysiology leading to disease progression and death. Low sensitivities and specificities prevent outcome prediction in individual cats.     

Outcomes of esophageal and gastric bone foreign bodies in dogs

BackgroundBone foreign bodies are commonly encountered in small animal practice. Esophageal bone foreign bodies (E‐bFBs) warrant removal, whereas gastric bone foreign bodies might not.ObjectivesDescribe management and outcomes for dogs with esophageal or gastric bone foreign bodies.AnimalsOne hundred twenty‐nine dogs with esophageal (n = 45) or gastric (n = 84) bone foreign bodies.MethodsRetrospective review of medical records.ResultsDogs with E‐bFBs were younger than dogs with gastric bone foreign bodies (median age esophageal, 4 years [IQR 2‐8]; median age gastric, 6 years [IQR 3‐10]; P = .03), and had a higher bone cross‐sectional area relative to body weight (median esophageal, 98.21 mm²/kg [IQR 48.25‐142.6]; median gastric, 28.6 mm²/kg [IQR 17.25‐64.28]; P < .001). Forty‐two of 45 esophageal foreign bodies were resolved non‐surgically and 3 by esophagotomy. Esophageal erosions were more likely with distal entrapment (OR 12.88, [95% CI 31.95‐129.29], P = .01) and longer duration (OR 18.82 [95% CI 2.22‐273.97], P = .01). Sixty‐two of 84 bone gastric foreign bodies were left in situ. Endoscopic removal was successful in 20 of 22 (91%; 95% CI 70‐99) attempts.Conclusions and Clinical ImportanceWhile all E‐bFBs were dislodged either by advancement into the stomach, endoscopic removal, or esophagotomy, the majority of gastric bone foreign bodies were left in situ for dissolution, with no reported complications. Gastric advancement of E‐bFBs should be considered when oral removal is not feasible, and dissolution can be considered even with large bones.     

Serial evaluation of thoracic radiographs and acute phase proteins in dogs with pneumonia

BackgroundAcute phase proteins (APP) may guide treatment of pneumonia in dogs but correlations with radiographic abnormalities are poorly characterized.ObjectivesDevelop a thoracic radiographic severity scoring system (TRSS), assess correlation of radiographic changes with APP concentrations, and compare time to APP and radiograph normalization with duration of antimicrobials treatment.AnimalsSixteen client‐owned dogs, 12 with aspiration pneumonia, and 4 with community‐acquired pneumonia.MethodsConcentrations of C‐reactive protein (CRP), serum amyloid A (SAA), and haptoglobin were measured on days 1, 3, 7, 14, 28, and 60 and orthogonal 2‐view thoracic radiographs were obtained on days 1, 7, 14, 28, and 60. Treatment was clinician‐guided and blinded to APP concentrations. Radiographic severity scores were assigned by blinded, randomized retrospective review by 2 board‐certified radiologists with arbitration by a third radiologist.ResultsMedian (interquartile range [IQR]) time to normalization of CRP (7 days [7‐14]) and SAA concentrations (7 days [7‐14]) were shorter than antimicrobial treatment duration (17.5 days [14.5‐33.5]; P = .001 and .002, respectively) and TRSS normalization (14 days [8.8‐52], P = .02 and .02, respectively). The CRP and SAA concentrations were positively correlated with TRSS (CRP r _s , 0.643; SAA r _s , 0.634; both P < .0001). Both CRP and SAA identified normal thoracic radiographs area under the curve (AUC) 0.873 and 0.817, respectively, both P < .0001. Interobserver agreement for TRSS assignment was moderate (κ, .499; P < .0001).Conclusion and Clinical ImportanceConcentrations of CRP and SAA normalized before radiographic resolution and before clinicians discontinued antimicrobial treatment. The CRP and SAA concentrations may guide duration of antimicrobial treatment for dogs with pneumonia.     

Serotonin Concentrations in Platelets,Plasma, Mitral Valve Leaflet,and Left Ventricular Myocardial Tissue in Dogs with Myxomatous Mitral Valve Disease

Hypothesis/Objectives

Altered serotonin (5‐hydroxytryptamine, 5HT) signaling is postulated in development and progression of canine myxomatous mitral valve disease (MMVD). Little is known regarding platelet, plasma, valvular, or myocardial 5HT concentration ([5HT]) in affected dogs. We quantified [5HT] in platelet‐rich plasma (PRP), platelet‐poor plasma (PPP), mitral valve leaflets (MV), and left ventricular myocardium (LV).

Animals

Forty‐five dogs comprised 4 plasma groups of Cavalier King Charles Spaniels (CKCS) or non‐CKCS, either healthy (CON) or MMVD affected: CKCS CON (n = 12); non‐CKCS CON (n = 8); CKCS MMVD (n = 14); non‐CKCS MMVD (n = 11). Twenty‐four dogs comprised 3 tissue groups: MMVD (n = 8); other‐HD (heart disease) (n = 7); non‐HD, extracardiac disease (n = 9).

Methods

High‐performance liquid chromatography measured PRP, PPP, MV, and LV [5HT].

Results

Platelet‐rich plasma platelet [5HT] was greater in CKCS CON (1.83 femtograms/platelet [fg/plt]; range, 0.20–4.76; P = .002), CKCS MMVD (1.58 fg/plt; range, 0.70–4.03; P = .005), and non‐CKCS MMVD (1.72 fg/plt; range, 0.85–4.44; P = .003) versus non‐CKCS CON (0.92 fg/plt; range, 0.63–1.30). There was no group difference in PPP [5HT]. MV [5HT] was significantly higher in MMVD (32.4 ng/mg; range, 8.4–106.7) versus non‐HD (3.6 ng/mg; range, 0–28.3; P = .01) and LV [5HT] was significantly higher in MMVD (11.9 ng/mg; range, 4.0–104.8) versus other‐HD (0.9 ng/mg; range, 0–10.1; P = .011) and non‐HD (2.5 ng/mg; range, 0–6.9; P = .001).

Conclusions and Clinical Importance

Platelet [5HT] was highest in healthy CKCS and both MMVD groups, but plasma [5HT] showed no group differences. Tissue [5HT] was highest in MV and LV of MMVD‐affected dogs, suggesting altered 5HT signaling as a potential feature of MMVD. Interactions of platelet, valvular, and myocardial 5HT signaling warrant further investigation.     

Blood plasma concentrations of oestradiol-17β, testosterone and testosterone/oestradiol ratio in dogs with neoplastic and degenerative testicular diseases

Oestradiol-17β and testosterone blood plasma concentrations were measured in dogs with Leydig-cell tumours (n=20), Sertoli-cell tumours (n=6), seminomas (n=9), unilateral inguinal cryptorchidism (n=7), abdominal cryptorchidism (n=9, one bilateral), degenerate scrotal testicles (n=6, two bilateral), and animals with normal scrotal testicles (n=20). The testosterone/oestradiol ratio (testosterone concentration [ng/mL] × 100/oestradiol concentration [pg/mL]) was calculated.A considerably higher oestradiol concentration was found in dogs with Sertoli-cell tumours (29.0, 14.4–48.3 pg/mL; median, minimum–maximum; P=0.0256, Mann–Whitney test) and lower oestradiol levels were found in animals with seminomas (12.0, 3.4–17.6 pg/mL; P=0.0025) compared to the healthy control group (18.0, 8.6–31.5 pg/mL). Testosterone concentration was decreased in dogs with Sertoli-cell tumours (0.08, 0.03–0.77 ng/mL) when compared to the control group (1.95, 0.05–3.70 ng/mL; P=0.0012). Testosterone/oestradiol ratios differed from the control (9.6, 0.58–35.8) only in dogs with Sertoli-cell tumours (0.32, 0.06–2.80; P=0.0005). Clinical signs of feminization were observed in five dogs with Sertoli-cell tumour and one dog with a Leydig-cell tumour, and were more often associated with decreased testosterone/oestradiol ratios than with an increased oestradiol-17β concentration.     

Effects of Pioglitazone on Insulin Sensitivity and Serum Lipids in Obese Cats

Background

Pioglitazone is a thiazolidinedione (TZD) insulin sensitizer approved for use in human type 2 diabetes mellitus. Therapeutic options for diabetes in cats are limited.

Objective

To evaluate the effects of pioglitazone in obese cats, which are predisposed to insulin resistance, to assess its potential for future use in feline diabetes mellitus.

Animals

A total of 12 obese purpose‐bred research cats (6 neutered males and 6 spayed females, 5–7 years of age, weighing 5.4–9.8 kg).

Methods

Randomized, placebo‐controlled 3‐way crossover study. Oral placebo or pioglitazone (Actos™; 1 or 3 mg/kg) was administered daily for 7‐week periods, with IV glucose tolerance testing before and after each period.

Results

Three mg/kg pioglitazone significantly improved insulin sensitivity (geometric mean [95% CI] 0.90 [0.64–1.28] to 2.03 [1.49–2.78] min ⁻¹pmol⁻¹L; P = .0014 versus change with placebo), reduced insulin area under the curve during IVGTT (geometric mean [range] 27 [9–64] to 18 [6–54] min∙nmol/L; P = .0031 versus change with placebo), and lowered serum triglyceride (geometric mean [range] 71 [29–271] to 48 [27–75] mg/dL; P = .047 versus change with placebo) and cholesterol (geometric mean [range] 187 [133–294] to 162 [107–249] mg/dL; P = .0042 versus change with placebo) concentrations in the obese cats. No adverse effects attributable to pioglitazone were evident in the otherwise healthy obese cats at this dosage and duration.

Conclusions and Clinical Importance

Results of this study support a positive effect of pioglitazone on insulin sensitivity and lipid metabolism in obese cats, and suggest that further evaluation of the drug in cats with diabetes mellitus or other metabolic disorders might be warranted.     

Acute kidney injury in dogs: Etiology,clinical and clinicopathologic findings,prognostic markers,and outcome

BackgroundAcute kidney injury (AKI) is a common, potentially fatal condition.ObjectivesTo characterize the etiologies, clinical and clinicopathologic findings, hospitalization period, and outcome of dogs with AKI and to identify markers of negative prognosis.AnimalsTwo hundred forty‐nine client‐own dogs diagnosed with AKI and hospitalized at a veterinary teaching hospital.MethodsRetrospective study. Search of medical records for dogs with AKI.ResultsCommon clinical signs included lethargy (225/249, 90%), anorexia (206/249, 83%), and vomiting (168/249, 68%). Etiologies included ischemic/inflammatory (144/249, 58%), infectious (19/249, 8%), nephrotoxicosis (14/249, 6%), or other (13/249, 5%). Hospital‐acquired AKI was diagnosed in 9% (23/249) of the dogs. Median presentation and peak serum creatinine (sCr) concentrations were 4 mg/dL (range, 1.1‐37.9) and 4.6 mg/dL (range, 1.1‐43.1), respectively. Dogs were classified to AKI grades as follows: Grade I, 6 (2%), Grade II, 38 (15%), Grade III, 89 (36%), Grade IV, 77 (31%), and Grade V, 39 (16%). One hundred and sixty‐four (66%) dogs survived. There was a positive association between death and AKI grade (P = .009). The case fatality rate was higher among dogs with anuria compared with dogs without anuria (50% vs 28%, respectively; odds ratio [95% confidence interval]: 2.5 [1.39‐4.6]; P = .002). Forty‐seven (18.8%) dogs underwent hemodialysis, of which 60% survived.Conclusion and Clinical ImportanceTwo‐thirds of dogs with AKI survived. Hospital‐acquired AKI was common. The severity of AKI, as reflected by presence of anuria, AKI grade, and other body organs involvement, was associated with the outcome.     

Changes in renin‐angiotensin‐aldosterone system during cardiac remodeling after mitral valvuloplasty in dogs

BackgroundInformation regarding changes in renin‐angiotensin‐aldosterone system (RAAS) during cardiac remodeling after mitral valvuloplasty (MVP) in dogs remains lacking.Hypothesis/ObjectivesTo assess the longitudinal effects of MVP on circulating RAAS activity.AnimalsEight client‐owned dogs receiving MVP for myxomatous mitral valve disease (MMVD).MethodsThis is a cohort study. Plasma renin activity (PRA), angiotensin II (AT2), aldosterone (PAC), blood urea nitrogen (BUN), and creatinine concentrations, were measured in these dogs before (baseline) and at 3 consecutive monthly follow‐ups (Post‐1M, Post‐2M, Post‐3M). Echocardiography was concomitantly used to assess the process of cardiac recovery after MVP.ResultsThe echocardiography revealed a significant decrease in LVIDDN, LA/Ao, FS, E velocity, E/A, E′ sep, S′ lat, E′ lat, and A′ lat after MVP compared with baseline (P < .05). There was a significant reduction in the PRA (2.45, 3.05, 2.74 vs 8.8 ng/mL/h; P = .002), AT2 (466, 315, 235 vs 1200 pg/mL; P = .009), and PAC (39.88, 47, 54.62 vs 179.5 pg/mL; P = .01), respectively at Post‐1M, Post‐2M, Post‐3M compared to the baseline. Additionally, BUN and creatinine concentrations decreased from Post‐1M. The RAAS variables showed significant, weak to moderate, relationship with selected echocardiographic variables.Conclusions and Clinical ImportanceMitral valvuloplasty contributes to decreased RAAS activity in MMVD dogs, which paralleled the process of cardiac reverse remodeling up to Post‐3M. This information facilitates formulating strategies to optimize clinical outcomes for dogs after MVP.     

Serum Concentrations of Gastrin after Famotidine and Omeprazole Administration to Dogs

Background

The duration of antacid‐induced hypergastrinemia after cessation of administration of omeprazole and famotidine apparently has not been determined in dogs.

Hypothesis

That serum gastrin will return to basal concentrations by 7 days after cessation of famotidine or omeprazole administration.

Animals

Nine healthy, adult, male, research colony dogs.

Methods

Randomized, cross‐over design. Serum gastrin was determined daily for 7 days to establish baseline concentrations. Famotidine (1.0 mg/kg q24h) or omeprazole (1.0 mg/kg q24h) was administered PO for 7 days followed by a 14‐day washout. Serum concentrations of gastrin were determined daily during 7 days of administration and daily for 7 days after cessation of administration. Each drug was evaluated in 8 of the 9 dogs.

Results

Omeprazole caused a significant increase in serum gastrin concentration (37.2 ± 7.3 to 71.3 ± 19.0 ng/L; P = .006). Famotidine induced a transient increase in serum gastrin (37.2 ± 7.3 to 65.5 ± 38.5 ng/L; P = .02) that peaked at administration day 3 and declined thereafter. By day 7 after cessation of both drugs, there was no difference in serum gastrin concentrations compared to those before administration (famotidine P = .99; omeprazole P = .99). During or after administration, gastrin concentrations above 3 times the upper reference range were rare (12 of 224 samples).

Conclusions and Clinical Importance

A 7‐day withdrawal from short‐term administration of famotidine or omeprazole is sufficient for serum gastrin to return to baseline concentrations. Withholding famotidine or omeprazole for longer before investigating pathologic causes of hypergastrinemia is unnecessary.     

Investigation of serum survivin in dogs suffering from cancer: a multicenter study

BackgroundIn contrast to human medicine, only a small number of serum tumor markers are established in veterinary medicine even though they are a non-invasive diagnostic tool.ObjectivesThis study examined whether survivin could be suitable as a potential canine serum tumor marker.MethodsThis study measured the serum survivin concentrations of dogs with mammary tumors (n = 33), squamous cell carcinoma (n = 9), soft-tissue sarcoma (n = 18) and multicentric lymphoma (n = 22), using a commercially available, competitive immunoassay kit (BlueGene). The serum survivin concentrations were compared with those of a healthy control group (n = 20) and a control group of dogs with non-neoplastic diseases (n = 17).ResultsDogs with malignant tumors had serum survivin concentrations between 15 and 5,906 pg/mL (median, 72 pg/mL), those in the healthy group ranged from 7 to 99 pg/mL (median, 21 pg/mL) and those in the group of dogs suffering from non-neoplastic diseases from 15 to 93 pg/mL (median, 42 pg/mL). The differences in the survivin concentrations between the healthy dogs and dogs with malignant tumors and between the dogs with non-neoplastic diseases and those with malignant tumors were significant (p < 0.001 and p = 0.006, respectively).ConclusionsThe serum survivin concentrations in dogs with malignant tumors, with some exceptions, are higher than in dogs with benign tumors and dogs that do not suffer from a malignancy. Therefore, survivin can provide information on the presence of malignant tumors and be used as a tumor marker in dogs.     

Evaluation of the Effects of a Therapeutic Renal Diet to Control Proteinuria in Proteinuric Non‐Azotemic Dogs Treated with Benazepril

Background

Angiotensin‐converting enzyme inhibitors (ACEIs) are currently used to control proteinuria in dogs with chronic kidney disease. Renal diets (RDs) have beneficial effects in the management of azotemic dogs, but its role in proteinuric non‐azotemic (PNAz) dogs has been poorly documented.

Hypothesis

Administration of a RD to PNAz dogs treated with benazepril (Be) improves proteinuria control compared with the administration of a maintenance diet (MD).

Animals

Twenty‐two PNAz (urine protein/creatinine ratio [UPC] >1) dogs.

Methods

Randomized open label clinical trial design. Dogs were assigned to group‐MD (5.5 g protein/100 kcal ME)/Be or to group‐RD (3.7 g protein/100 kcal ME)/Be group during 60 days. Dogs with serum albumin (Alb) <2 g/dL received aspirin (1 mg/kg/12 hours). A physical examination, systolic blood pressure (SBP) measurement, complete blood count (CBC), biochemistry panel, urinalysis, and UPC were performed at day 0 (D0) and day 60 (D60).

Results

At D0, there were no significant differences between groups in the evaluated variables. During the study, logUPC (geometric mean (95% CI) and SBP (mean±SD mmHg) significantly decreased (paired t‐test, P = 0.001) in Group‐RD (logUPC_D0 = 3.16[1.9–5.25]; UPC_D60 = 1.20 [0.59–2.45]; SBP_D0 = 160 ± 17.2; SBP_D60 = 151 ± 15.8), but not in Group‐MD (UPC_D0 = 3.63[2.69–4.9]; UPC_D60 = 2.14 [0.76–6.17]; SBP_D0 = 158 ± 14.7; SBP_D60 = 153 ± 11.5). However, RM‐ANOVA test did not confirm that changes were consequence of dietary modification. Weight and Alb concentration did not change significantly in any group.

Conclusion and Clinical Relevance

The administration of a RD to PNAz dogs treated with Be might help to control proteinuria and SBP compared with the administration of a MD, without inducing clinically detectable malnutrition, but more studies are warranted.     

Plasma and Urine Neutrophil Gelatinase–Associated Lipocalin (NGAL) in Dogs with Acute Kidney Injury or Chronic Kidney Disease

Background

Neutrophil gelatinase–associated lipocalin (NGAL) is a protein that is used in human medicine as a real‐time indicator of acute kidney injury (AKI).

Hypothesis

Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL‐to‐creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD).

Animals

18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI.

Methods

Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single‐injection plasma inulin clearance was performed in the healthy dogs.

Results

Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5–21.2), 22.0 ng/mL (7.7–62.3), and 48.3 ng/mL (5.7–469.0), respectively. UNCR was 2 × 10⁻⁸ (0–46), 1,424 × 10⁻⁸ (385–18,347), and 2,366 × 10⁻⁸ (36–994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027).

Conclusions and Clinical Importance

Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.     

Hypomagnesemia in Brachycephalic Dogs

Background

Brachycephalic dogs are at risk for arterial hypertension and obstructive sleep apnea, which are both associated with chronic magnesium (Mg) depletion.

Hypothesis/Objectives

To compare the period prevalence of hypomagnesemia between Boxers and Bulldogs presented to a referral teaching hospital. To screen a group of Bulldogs for evidence of hypomagnesemia, and to obtain pilot data regarding the utility of parenteral Mg tolerance testing (PMgTT) in the diagnosis of whole‐body Mg deficiency.

Animals

Chemistry laboratory submissions were retrospectively analyzed for serum total Mg (tMg) in Boxers and Bulldogs. Prospectively, 16 healthy client‐owned Bulldogs were enrolled.

Methods

Retrospective case study. tMg concentrations were compared between Boxers and Bulldogs. Dogs with low serum albumin or high serum creatinine concentrations were excluded. Prospectively, ionized Mg (iMg), tMg, and arterial blood pressure were measured and iMg‐to‐tMg ratio (iMg : tMg) was calculated. Parenteral Mg tolerance testing (PMgTT) was performed in 3/16 dogs.

Results

In the retrospective study, period prevalence of hypomagnesemia was 4.7% in Boxers and 15% in Bulldogs (P = .02). The risk ratio for hypomagnesemia in Bulldogs was 1.8 when compared to Boxers (CI: 1.3–2.7). In the prospective study, iMg was [median (interquartile)] 0.43 (0.42–0.46) mmol/L (reference range 0.4–0.52), tMg was 1.9 (1.8–1.9) mg/dL (reference range 1.9–2.5). iMg : tMg was [mean (±SD)] 0.59 ± 0.04. Percentage retention after PMgTT were 55%, 95%, and 67%, respectively.

Conclusions and Clinical Importance

Mg deficiency is common in Bulldogs and could contribute to comorbidities often observed in this breed. iMg : tMg and PMgTT might prove helpful in detecting chronic subclinical Mg deficiency.     

Evaluation of circulating IGF-I and IGFBP-3 as biomarkers for tumors in dogs

BackgroundSerum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets.ObjectivesThis study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors.MethodsThe serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA).ResultsThe ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5–175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5–79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2–57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6–70.5]) in healthy dogs.ConclusionsThe serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.