Endotoxic kidney injury in Beagle dogs assessed by serum creatinine and symmetric dimethylarginine, and urinary neutrophil gelatinase-associated lipocalin and clusterin.

Sepsis of Gram negative bacterial origin results in lipopolysaccharide-induced endotoxemia. This often leads to acute kidney injury (AKI) and its recognition remains a challenge and delays treatment. As renal damage occurs before a rise in serum creatinine is detected, new early biomarkers of kidney injury need to be explored. The aim of this study was to determine changes in serum parameters of renal function and urine biomarkers of renal injury. This was a descriptive study. Endotoxemia was induced intravenously in six anaesthetized Beagles (T1). To achieve normotension, dogs received fluids (T2), followed by a continuous infusion of noradrenaline and dexmedetomidine or 0.9% NaCl (T3). Ten minutes later, the dogs received fluids (T4) and noradrenaline and dexmedetomidine or 0.9% NaCl in a crossover manner (T5). At each timepoint, blood and urine were collected for serum creatinine, urea, symmetric dimethylarginine, urine protein/creatinine (UPC) ratio, urine neutrophil-gelatinase-associated lipocalin (U-NGAL), U-NGAL/creatinine ratio, urine clusterin (U-clusterin) and U-clusterin/creatinine ratio. Data were analyzed using a mixed-effect model taking into account time and stage of veterinary AKI (VAKI). Three of six dogs had a VAKI stage ≥1; one with anuria and elevated creatinine. Serum creatinine (P < 0.001), U-NGAL/creatinine ratio (P = 0.01) and U-clusterin/creatinine ratio increased over time (P < 0.01). The UPC ratio (mean (range) 0.68 (0.35-2.3) versus 0.39 (0.15-0.71) P < 0.01) and U-NGAL (3164 pg/mL (100-147,555) versus 100 (100-14,524), P = 0.01) were higher in VAKI stage ≥1 versus stage 0, respectively. Endotoxemia induced VAKI stage ≥1 in half of the dogs. Repeated measurement of selected parameters could detect AKI early.

131 treatment in dogs with hyperthyroidism caused by a non-resectable ectopic thyroid tumour: 5 cases (2008-2019).

OBJECTIVES: This study aimed to describe the clinical and diagnostic characteristics, as well as outcomes of radioiodine treatment in dogs with hyperthyroidism caused by a non-resectable ectopic thyroid tumour. MATERIALS AND METHODS: This retrospective study reviewed the medical records between 2008 and 2018 of dogs diagnosed with hyperthyroidism secondary to a non-resectable ectopic thyroid tumour and treated with radioiodine. RESULTS: Five dogs were included in the study. Three dogs had sublingual ectopic tumours, of which one also had a unilateral cervical thyroid tumour. The remaining two dogs were diagnosed with an ectopic thyroid tumour at the level of the caudal pharynx and the heart base, respectively. All cases were treated with radioiodine. The size of the ectopic masses decreased after radioiodine treatment. Total thyroxine concentrations returned to reference ranges in all dogs. Further, clinical signs of hyperthyroidism disappeared after treatment in all patients. One dog developed myelosuppression secondary to radioiodine treatment. The dog with metastasis had a very short survival compared to the four dogs without metastasis (3 months compared to 7, 36, 50 and 24 months, respectively) and succumbed most likely to thyroid-related problems. In the remaining four dogs, their quality of life improved. They died due to diseases unrelated to the ectopic thyroid tumour. CLINICAL SIGNIFICANCE: Radioiodine therapy should be considered as a treatment option in dogs diagnosed with hyperthyroidism due to a non-resectable ectopic thyroid tumour.

Evaluation of acute kidney injury in dogs with complicated or uncomplicated Babesia rossi infection.

Dogs with babesiosis can present with multiple complications, including acute kidney injury (AKI). The objective of this study was to characterize AKI in dogs with babesiosis caused by Babesia rossi at presentation and after treatment. Thirty-five client-owned dogs with B. rossi infection and 10 control dogs were included in this prospective observational study. Blood and urine were collected in Babesia-infected dogs at presentation (T0, n = 35), after 24 h (T24h, n = 11), and after 1 month (T1m, n = 9). The following urinary kidney injury biomarkers were assessed: urinary protein to creatinine ratio (UPC), urinary glomerular injury biomarkers (immunoglobulin G (uIgG) and C-reactive protein (uCRP)), and urinary tubular injury biomarkers (retinol-binding protein (uRBP) and neutrophil gelatinase-associated lipocalin (uNGAL)). Serum functional renal biomarkers were creatinine (sCr) and symmetric dimethylarginine (sSDMA). Post-mortem kidney biopsies were analyzed by light and transmission electron microscopy. At T0, all kidney injury biomarkers were significantly higher in Babesia-infected dogs compared to healthy controls (P < 0.001), while functional renal biomarkers were not significantly different (P > 0.05). At T24h, all urinary tubular injury biomarkers and UPC decreased significantly (P < 0.01), while glomerular injury biomarkers did not (P = 0.084). At T1m, all urinary kidney injury biomarkers decreased to values not significantly different from healthy controls (P > 0.5). Significant changes in functional renal biomarkers were not seen after treatment (P > 0.05). Dogs with complicated babesiosis had significantly higher glomerular injury biomarkers, UPC, and sSDMA compared to uncomplicated cases (P < 0.05), while all tubular injury biomarkers and sCr were not significantly different (P > 0.1). Dogs with babesiosis caused by B. rossi showed transient kidney injury, which was detected by all kidney injury biomarkers, but remained undetected by functional biomarkers. All infected dogs, irrespective of disease severity, suffered comparable kidney injury based on tubular injury biomarker concentrations, while loss of function was seen more often in dogs with complicated babesiosis based on sSDMA results.

Urinary neutrophil gelatinase-associated lipocalin as an early biomarker for acute kidney injury in dogs.

Neutrophil gelatinase-associated lipocalin (NGAL) is used as an early biomarker of renal injury in people. In dogs, increases in urinary NGAL (uNGAL) precede increases in serum creatinine (sCr) in experimental and clinical evaluations of acute kidney injury (AKI) and chronic kidney disease. This study compared uNGAL in two subsets of dogs with AKI and their respective controls. One set included dogs with snake-envenomation at risk for or presenting with International Renal Interest Society (IRIS) grade I AKI; the other group included dogs with AKI, where renal injury was the result of various causes, and IRIS grade was ≥II. Additionally, this study evaluated haemoglobin (Hb) interference during NGAL analysis in Hb spiked urine and plasma from healthy dogs. In both AKI groups, uNGAL was significantly higher than in matched healthy control dogs (P<0.01). Moreover, uNGAL was significantly higher in dogs with IRIS grade ≥II AKI than in dogs at risk of IRIS grade I AKI (P=0.04). In dogs at risk of IRIS grade I AKI, there were no significant differences in uNGAL and uNGAL/uCr between dogs bitten by cytotoxic or neurotoxic snakes (P=0.44). Additionally, Hb did not interfere with the canine NGAL immunoassay. In conclusion, this study confirms the value of uNGAL as a biomarker for early renal damage: uNGAL was significantly increased in dogs with snake-envenomation at risk for or presenting with IRIS grade I AKI, which could be left undiagnosed if evaluated with the traditional renal biomarker sCr. In addition, Hb did not interfere with NGAL measurement in dogs.

Assessment of acute kidney injury in canine parvovirus infection: Comparison of kidney injury biomarkers with routine renal functional parameters.

Dogs with naturally occurring canine parvovirus (CPV) infection are at risk of developing acute kidney injury (AKI) due to several factors, including severe dehydration, hypotension and sepsis. Serum creatinine (sCr) and serum urea are insensitive markers for the assessment of early kidney injury. Therefore, the aim of this study was to investigate potential kidney injury in dogs with CPV infection using both routine renal functional parameters and several kidney injury biomarkers. Twenty-two dogs with CPV infection were prospectively enrolled and compared with eight clinically healthy control dogs. Urinary immunoglobulin G (uIgG) and C-reactive protein (uCRP) were measured to document glomerular injury, whereas urinary retinol-binding protein (uRBP) and neutrophil gelatinase-associated lipocalin (uNGAL) served as markers for tubular injury. These biomarkers were compared to routine renal functional parameters, including sCr, serum urea, urinary protein:creatinine ratio (UPC) and urine specific gravity (USG). Dogs with CPV infection had significantly higher concentrations of uIgG, uCRP, uRBP and uNGAL compared to healthy dogs. In contrast, sCr was significantly lower in dogs with CPV infection compared to controls, while serum urea was not significantly different. UPC and USG were both significantly higher in CPV-infected dogs. This study demonstrated that dogs with CPV infection had evidence of AKI, which remained undetected by the routine functional markers sCr and serum urea, but was revealed by UPC, uIgG, uCRP, uRBP and uNGAL. These results emphasize the added value of novel urinary kidney injury biomarkers to detect canine patients at risk of developing AKI.

Variability of serum concentrations of cystatin C and urinary retinol-binding protein, neutrophil gelatinase-associated lipocalin, immunoglobulin G, and C-reactive protein in dogs.

BACKGROUND: Markers of kidney dysfunction and damage have potential to detect chronic kidney disease (CKD) in early stages. However, data on long-term variation of these markers in healthy dogs is lacking and is crucial for the interpretation of results. HYPOTHESIS/OBJECTIVES: To determine temporal variations of serum cystatin C (sCysC) and urinary retinol-binding protein (uRBP), neutrophil gelatinase-associated lipocalin (uNGAL), immunoglobulin G (uIgG), and C-reactive protein (uCRP) in healthy dogs. ANIMALS: Eight clinically healthy adult Beagles were evaluated. METHODS: Longitudinal observational study. Serum cystatin C was determined by particle-enhanced nephelometric immunoassay. Urinary retinol-binding protein, uNGAL, uIgG and uCRP were determined by ELISA and concentrations were indexed to urinary creatinine. Within- and between-dog variance components (VC) and within-dog coefficients of variation (CV) were determined from blood and urine collected at eight time points over 1.5 years. RESULTS: Urinary C-reactive protein (uCRP) concentrations were consistently below the detection limit (5.28 ng/mL). Mean ± within-dog standard deviation for sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 ± 0.01 mg/L, 0.09 ± 0.03 mg/g, 2.32 ± 2.03 µg/g and 12.47 ± 10.98 mg/g, respectively. Within-dog CV for sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c exhibit a wide range of long-term within-dog variability. Researchers and veterinarians might need to take this into account when interpreting their results. To assess their diagnostic and predictive ability, future studies need to establish reference ranges for healthy dogs and dogs with CKD.

Renal azotemia and associated clinical and laboratory findings in dogs with Babesia rossi infection.

The occurrence of acute kidney injury in canine babesiosis is not well documented. Furthermore, interpretation of urine specific gravity (USG) to assess renal concentrating ability is hampered by the frequent presence of hemoglobinuria in this disease. This cross-sectional study aimed to test the hypothesis that renal azotemia (RA) is underdiagnosed according to current canine babesiosis literature by determining its occurrence at presentation, using urine osmolality instead of USG to measure urinary concentration. The second objective was to examine potential associations between the presence of RA and selected clinical and laboratory variables at presentation. Medical records available from 3 previously performed prospective data collections were reviewed retrospectively. Client-owned dogs that were diagnosed with babesiosis caused by Babesia rossi, were included if a complete blood count, biochemistry profile, and urinalysis was performed at admission. Urine osmolality was measured to identify dogs with RA. Differences between dogs with RA and dogs without RA were assessed by nonparametric statistics. One hundred and fifty-two dogs were included, of which 26 (17%) were azotemic at admission. The occurrence of RA was 14% (21/152), hence 81% (21/26) of all azotemic dogs were diagnosed with RA. In contrast, when diagnosis of RA was based on an admission USG < 1.030, only 23% (6/26) of the azotemic dogs would have been considered to have RA. Several signalment and clinicopathological findings were found to be associated with the presence of RA, including older age, and the presence of collapse, hypoglycemia, hyperphosphatemia, cerebral babesiosis, and acute respiratory distress syndrome. Lastly, survival at discharge was significantly lower in dogs diagnosed with RA at presentation. Our results clarified that RA is more common than previously reported in B. rossi. This study also demonstrated that USG determination is not a reliable method to evaluate renal concentrating ability in azotemic dogs with babesiosis. Thus, if available, urine osmolality should be part of the diagnostic work-up of dogs infected with B. rossi to avoid misclassification of dogs with RA as having prerenal azotemia. If urine osmolality cannot be measured, clinicians should realize that most azotemic dogs with B. rossi infection have RA.

A single dose of intravenous combretastatin A4-phosphate is reasonably well tolerated and significantly reduces tumour vascularization in canine spontaneous cancers.

Combretastatin A4-phosphate (CA4P) is an anti-tumour vascular targeting agent which selectively blocks tumour blood flow. Research on CA4P in rodent tumour models is extensive; however, knowledge of its effect on spontaneous cancer is scarce. This study was conducted in canine patients with spontaneous solid tumours. The goal was to assess the toxicity and efficacy of CA4P in various spontaneous tumour types. Eight dogs with spontaneous tumours were enrolled and treated with a single dose of 75 mg m-2 intravenous CA4P. The dogs were screened and monitored before and after injection. Pre- and post-treatment tumour blood flow was analysed in vivo by power Doppler ultrasound (PDUS) and contrast-enhanced ultrasound (CEUS). Vessel destruction and tumour necrosis were evaluated by histopathology. Clinically relevant toxicity was limited to one case of temporary tetraparesis; other adverse events were mild. Significant cardiovascular changes were mostly confined to changes in heart rate and cTnI levels. Macroscopic tumour size reduction was evident in 2 dogs. Based on PDUS and CEUS, CA4P induced a significant decrease in vascular index and tumour blood flow. Post-treatment, histopathology revealed a significant increase of necrotic tumoural tissue and a significant reduction in microvessel density in tumoural tissue. Anti-vascular and necrotizing effects of CA4P were documented in a variety of canine spontaneous cancers with only minimal side effects. This is the first study reporting the administration of CA4P to canine cancer patients with in vivo and ex vivo assessment, and a first step toward implementing CA4P in combination therapies in veterinary oncology patients. The use of CA4P in canine patients was approved and registered by the Belgian Federal Agency for Medicines and Health Products (FAMHP) (approval number 0002588, registration number 6518 ID 2F12).

Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 µSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients.

Contrast-Enhanced Ultrasound Examination for the Assessment of Renal Perfusion in Cats with Chronic Kidney Disease.

BACKGROUND: Contrast-enhanced ultrasound examination (CEUS) is a functional imaging technique allowing noninvasive assessment of tissue perfusion. Studies in humans show that the technique holds great potential to be used in the diagnosis of chronic kidney disease (CKD). However, data in veterinary medicine are currently lacking. OBJECTIVES: To evaluate renal perfusion using CEUS in cats with CKD. ANIMALS: Fourteen client-owned cats with CKD and 43 healthy control cats. METHODS: Prospective case-controlled clinical trial using CEUS to evaluate renal perfusion in cats with CKD compared to healthy control cats. Time-intensity curves were created, and perfusion parameters were calculated using off-line software. A linear mixed model was used to examine differences between perfusion parameters of cats with CKD and healthy cats. RESULTS: In cats with CKD, longer time to peak and shorter mean transit times were observed for the renal cortex. In contrast, a shorter time to peak and rise time were seen for the renal medulla. The findings for the renal cortex indicate decreased blood velocity and shorter total duration of enhancement, likely caused by increased vascular resistance in CKD. Increased blood velocity in the renal medulla has not been described before and may be because of a different response to regulatory factors in cortex and medulla. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrast-enhanced ultrasound examination was capable of detecting perfusion changes in cats with CKD. Further research is warranted to assess the diagnostic capabilities of CEUS in early stage of the disease process.

A dose-escalation study of combretastatin A4-phosphate in healthy dogs.

Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m-2 . At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low-grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m-2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m-2 , low-grade hypertension and high-grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m-2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m-2 , although transient, does not invite to use this dose in canine oncology patients.

Evaluation of Renal Perfusion in Hyperthyroid Cats before and after Radioiodine Treatment.

BACKGROUND: Hyperthyroidism and chronic kidney disease (CKD) are common in elderly cats. Consequently, both diseases often occur concurrently. Furthermore, renal function is affected by thyroid status. Because changes in renal perfusion play an important role in functional renal changes in hyperthyroid cats, investigation of renal perfusion may provide novel insights. OBJECTIVES: To evaluate renal perfusion in hyperthyroid cats with contrast-enhanced ultrasound (CEUS). ANIMALS: A total of 42 hyperthyroid cats was included and evaluated before and 1 month after radioiodine treatment. METHODS: Prospective intrasubject clinical trial of contrast-enhanced ultrasound using a commercial contrast agent (SonoVue) to evaluate renal perfusion. Time-intensity curves were created, and perfusion parameters were calculated by off-line software. A linear mixed model was used to examine differences between pre- and post-treatment perfusion parameters. RESULTS: An increase in several time-related perfusion parameters was observed after radioiodine treatment, indicating a decreased blood velocity upon resolution of the hyperthyroid state. Furthermore, a small post-treatment decrease in peak enhancement was present in the renal medulla, suggesting a lower medullary blood volume. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrast-enhanced ultrasound indicated a higher cortical and medullary blood velocity and higher medullary blood volume in hyperthyroid cats before radioactive treatment in comparison with 1-month post-treatment control.

Results of Screening of Apparently Healthy Senior and Geriatric Dogs.

BACKGROUND: There is a growing interest in health care of elderly dogs; however, scientific information about physical and laboratory examination findings in this age group is limited. OBJECTIVES: To describe systolic blood pressure (SBP), and results of physical examination and laboratory tests in senior and geriatric dogs that were judged by the owner to be healthy. ANIMALS: Hundred client-owned dogs. METHODS: Dogs were prospectively recruited. Owners completed a questionnaire. SBP measurement, physical, orthopedic and neurologic examination, direct fundoscopy and Schirmer tear test were performed. Complete blood count, serum biochemistry, and urinalysis were evaluated. RESULTS: Forty-one senior and 59 geriatric dogs were included. Mean SBP was 170 ± 38 mmHg, and 53 dogs had SBP > 160 mmHg. Thirty-nine animals were overweight. A heart murmur was detected in 22, severe calculus in 21 and 1 or more (sub)cutaneous masses in 56 dogs. Thirty-two dogs had increased serum creatinine, 29 hypophosphatemia, 27 increased ALP, 25 increased ALT, and 23 leukopenia. Crystalluria, mostly amorphous crystals, was commonly detected (62/96). Overt proteinuria and borderline proteinuria were detected in 13 and 18 of 97 dogs, respectively. Four dogs had a positive urine bacterial culture. Frequency of orthopedic problems, frequency of (sub)cutaneous masses, and platelet count were significantly higher in geriatric compared with senior dogs. Body temperature, hematocrit, serum albumin, and serum total thyroxine concentration were significantly lower in geriatric compared with senior dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Physical and laboratory abnormalities are common in apparently healthy elderly dogs. Veterinarians play a key role in implementing health screening and improving health care for elderly pets.

Proteinuria in Apparently Healthy Elderly Dogs: Persistency and Comparison Between Free Catch and Cystocentesis Urine.

BACKGROUND: Up to 25% of elderly humans have proteinuria, often associated with underlying lesions. Data concerning the presence of proteinuria in elderly dogs is scarce. OBJECTIVES: To describe the presence and persistence of proteinuria and to compare urinary protein : creatinine ratio (UPC) between free catch and cystocentesis urine samples in apparently healthy elderly dogs. ANIMALS: Hundred apparently healthy elderly dogs. METHODS: Prospective study. Owners of 100 elderly dogs were asked to collect 2 free catch urine samples. Dogs were considered healthy based on owner's perception and an age chart, based on ideal bodyweight, was used to define dogs as senior or geriatric. UPC of urine collected by free catch and cystocentesis were compared. Overt proteinuria and borderline proteinuria were defined as UPC >0.5 and between 0.2 and 0.5, respectively, if examination of sediment did not explain proteinuria. Proteinuria was considered persistent if present at both sampling times. RESULTS: At baseline, 71 owners succeeded in collecting urine. Eleven percent of dogs had overt proteinuria, 14% were borderline proteinuric, and 75% nonproteinuric. Thirty-seven repeated urine samples, with a median time interval of 31 days (range 10-90), were available. Nineteen percent of dogs had a persistently increased UPC (>0.2), with persistent overt proteinuria present in 8%. A strong correlation (ρ = 0.88) was found between UPC of urine collected by free catch and cystocentesis. CONCLUSIONS AND CLINICAL IMPORTANCE: As 19% of study dogs had persistent proteinuria, our findings emphasize that measurement of proteinuria should be part of geriatric health screening. For UPC in dogs, free catch urine provides a good alternative to cystocentesis.

Combretastatin A4-phosphate and its potential in veterinary oncology: a review.

For many years, research on anticancer therapy has focussed almost exclusively on targeting cancer cells directly, to selectively kill them or restrict their growth. But limited advances in this strategy have led researchers to shift their attention to other potential targets. Active research is now on-going on targeting tumour stroma. Vascular disrupting agents (VDAs) appear a promising class of anticancer drugs that are currently under investigation as a sole or combined therapy in human cancer patients. This article will briefly touch on the history and biology of combretastatin A4-phosphate (CA4P) as a typical example of VDAs and will concentrate on the side effects that can be expected when used in veterinary patients. Particularly, the pathogenesis of these side effects and how they may be prevented and/or treated will be discussed. The purpose of this article is to illustrate the potentials of CA4P as anticancer therapy in veterinary oncology patients.

Immunological and angiogenic markers during metronomic temozolomide and cyclophosphamide in canine cancer patients.

Metronomic chemotherapy stimulates the immune response via depletion of regulatory T cells (Tregs) and suppresses angiogenesis by modulating the secretion of thrombospondin-1 (TSP-1) and vascular endothelial growth factor (VEGF). In this study, blood was collected from 10 healthy dogs and from 30 canine cancer patients before and 2 and 4 weeks after treatment with metronomic temozolomide (6.6 mg m-2 ), cyclophosphamide (12.5 mg m-2 ) or cyclophosphamide and temozolomide. The percentage of circulating CD25+ Foxp3+ CD4+ Tregs and the plasma levels of TSP-1 and VEGF were measured. There was a significant difference in the percentage of Tregs between cancer patients and healthy dogs. A significant decrease in Tregs was noted in patients treated with metronomic cyclophosphamide and the combination. Treatment with temozolomide had no effect on the percentage of Tregs. TSP-1 and VEGF levels were, respectively, significantly lower and higher in cancer patients than in healthy dogs, but they were not influenced by any of the studied metronomic treatment regimens.

Evaluation of Cystatin C for the Detection of Chronic Kidney Disease in Cats.

BACKGROUND: Serum cystatin C (sCysC) and urinary cystatin C (uCysC) are potential biomarkers for early detection of chronic kidney disease (CKD) in cats. An in-depth clinical validation is required. OBJECTIVES: To evaluate CysC as a marker for CKD in cats and to compare assay performance of the turbidimetric assay (PETIA) with the previously validated nephelometric assay (PENIA). ANIMALS: Ninety cats were included: 49 CKD and 41 healthy cats. METHODS: Serum CysC and uCysC concentrations were prospectively evaluated in cats with CKD and healthy cats. Based on plasma exo-iohexol clearance test (PexICT), sCysC was evaluated to distinguish normal, borderline, and low GFR. Sensitivity and specificity to detect PexICT < 1.7 mL/min/kg were calculated. Serum CysC results of PENIA and PETIA were correlated with GFR. Statistical analysis was performed using general linear modeling. RESULTS: Cats with CKD had significantly higher mean ± SD sCysC (1.4 ± 0.5 mg/L) (P < .001) and uCysC/urinary creatinine (uCr) (291 ± 411 mg/mol) (P < .001) compared to healthy cats (sCysC 1.0 ± 0.3 and uCysC/uCr 0.32 ± 0.97). UCysC was detected in 35/49 CKD cats. R(2) values between GFR and sCysC or sCr were 0.39 and 0.71, respectively (sCysC or sCr = µ + GFR + Îµ). Sensitivity and specificity were 22 and 100% for sCysC and 83 and 93% for sCr. Serum CysC could not distinguish healthy from CKD cats, nor normal from borderline or low GFR, in contrast with sCr. CONCLUSION: Serum CysC is not a reliable marker of reduced GFR in cats and uCysC could not be detected in all CKD cats.

The effect of imepitoin, a recently developed antiepileptic drug, on thyroid parameters and fat metabolism in healthy Beagle dogs.

Since early 2013, imepitoin has been used in most European countries for the management of recurrent single generalised epileptic seizures in dogs with idiopathic epilepsy. It has been reported that imepitoin is as effective as phenobarbital (PB) in controlling seizures in dogs with newly diagnosed idiopathic epilepsy and it has a clinically superior safety profile. As the use of imepitoin gains popularity, its effect on serum thyroid parameters warrants further investigation since long-term PB administration influences thyroid parameters in dogs, which could lead to misinterpretation of laboratory results and incorrect diagnosis of thyroidal illness. A prospective study was conducted to compare the effect of orally administered PB and imepitoin on serum concentrations of total thyroxine (TT4), triiodothyronine, free thyroxine, thyroglobulin autoantibodies, thyroid-stimulating hormone, cholesterol and triglycerides in healthy Beagle dogs. These parameters were determined prior to and at 6, 12 and 18 weeks after antiepileptic drug administration. The starting dose of PB (5 mg/kg PO twice daily; range, 4.4-6.0 mg/kg) was monitored and adjusted to obtain optimal therapeutic serum concentrations (30-35 g/mL). Imepitoin was administered at 30 mg/kg PO twice daily (range, 29.2-35.7 mg/kg). Imepitoin administration did not affect any of the thyroid parameters over an 18-week period. In contrast, serum TT4 concentrations decreased significantly over time in dogs receiving PB (P <0.05). Serum cholesterol concentrations increased significantly over time in dogs in the imepitoin group, but not to the same extent as commonly seen in dogs with primary hypothyroidism.