Phosphocalcic metabolism and its potential association with biomarkers of kidney disease in dogs with spontaneous hyperadrenocorticism.

The pathogenesis of increased serum phosphate concentration and proteinuria in dogs with spontaneous hyperadrenocorticism (HAC) is unclear. A potential link between proteinuria and calcium/phosphate metabolism has never been studied in dogs with HAC. The aims of the study were: (1) To evaluate calcium/phosphate metabolism in dogs with spontaneous HAC and compare to healthy dogs as well as to dogs with non-HAC illness; (2) to look for associations between markers of calcium/phosphate metabolism and biomarkers of kidney disease in dogs with HAC. Fifty-four dogs were included in the study, classified as HAC (n=27), non-HAC disease (n=17), and healthy (n=10). Serum calcium, phosphate, 25(OH)Vitamin D, 1,25(OH)2Vitamin D, plasma intact parathyroid hormone concentration (iPTH), FGF23, and urinary fractional excretion of calcium and phosphate were evaluated in all dogs at diagnosis and compared between each group. The correlation between these variables and urine protein-to-creatinine ratio (UPC) and urinary N-acetylglucosaminidase-to-creatinine ratio (uNAG/C) was evaluated in the HAC group. Medians [range] of serum phosphate concentration, urinary fractional excretion of calcium (FE(Ca)), and iPTH were significantly higher in dogs with HAC than in dogs with non-HAC illness (P<0.01) and healthy dogs (P<0.01). Increased 1,25(OH)2Vitamin D/25(OH)Vitamin D was also observed (P<0.001). In HAC group, UPC was significantly negatively correlated with 25(OH)Vitamin D (r(s): -0.54; P<0.01). Urinary NAG/C was significantly positively correlated with serum phosphate (r(s): 0.46; P=0.019). Increased serum phosphate, urinary excretion of calcium, and hyperparathyroidism were observed in dogs with HAC. Vitamin D metabolism may be shifted towards increased 1-alpha hydroxylation.

Description of serum symmetric dimethylarginine concentration and of urinary SDS-AGE pattern in dogs with ACTH dependent hyperadrenocorticism.

Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4-132.6; 79.2-114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5-12; 7-9]; sCr, 57.2 µmol/L [35.2-212.2; 52.8-92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7-13; 8-10]; sCr, 70.4 µmol/L [61.6-79.2; 61.6-70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment.

Feline ureteral rupture with para-ureteral urinomas following blunt trauma: clinical presentation and long-term outcome after treatment by urinary diversion for five cases from 2012 to 2019.

CASE HISTORY: Medical records were reviewed for cats that underwent surgical treatment of traumatic ureteral rupture (TUR) using urinary diversion procedures between 2012 and 2019. CLINICAL FINDINGS AND TREATMENT: Five cats had presented with injuries associated with road traffic accidents. These included three cats with abdominal hernias that required surgical management. At a median of 15 days after the accident, cats represented with lethargy, the presence of an abdominal mass or with lower urinary tract symptoms and in all cats contrast diagnostic imaging showed proximal unilateral TUR with associated para-ureteral urinoma. Four cats received subcutaneous ureteral bypass (SUB) device placement and one had ureteral anastomosis over a stent. Unilateral cyst-like retroperitoneal fluid consistent with para-ureteral urinoma was observed in all cats and a diffuse retroperitoneal haematoma was noticed in four cats. No immediate major complications occurred, and all cats had post-operative serum creatinine concentration within the reference interval. The cat that had received a ureteral stent subsequently required placement of a SUB following stent encrustation 15 months after surgery. Median follow-up time was 34 (min 28, max 58) months and renal function was normal in all cats at the last follow-up. CLINICAL RELEVANCE: Urinary diversion procedures provided long-term stable renal function following proximal TUR in these five cats. Delayed, subtle non-specific clinical signs subsequent to high-energy blunt trauma causing abdominal hernia and associated diffuse retroperitoneal haematoma, should raise suspicion of TUR. ABBREVIATIONS: AFAST: Abdominal focused assessment with sonography for trauma; SUB: Subcutaneous ureteral bypass; TUR: Traumatic ureteral rupture.

Treatment of urinary incontinence in a cat with genitourinary dysplasia using an urethral sphincter occluder.

A 2-year-old spayed female Maine Coon presented with urinary incontinence and recurrent urinary tract infection since 2 months of age. Clinical examination was unremarkable. Ultrasonography, CT and cystourethroscopy revealed urogenital abnormalities consistent with genitourinary dysplasia. Urethral pressure profilometry suggested urethral sphincter mechanism incompetence. Surgical placement of an artificial urethral sphincter occluder was performed. Mild decrease of urinary incontinence was observed 6 weeks postoperatively. Inflation of the occluder under urethral pressure profilometry was subsequently performed and resolved the incontinence. This is the first report to describe the use of urodynamic testing at the time of inflation of an artificial urethral sphincter occluder to adjust the degree of urethral occlusion.

Clinical description of Corynebacterium urealyticum urinary tract infections in 11 dogs and 10 cats.

OBJECTIVES: To examine the clinical signs, laboratory findings, possible predisposing factors, antimicrobial sensitivity and outcomes of dogs and cats diagnosed with urinary tract infection caused by Corynebacterium urealyticum. MATERIALS AND METHODS: Retrospective, observational study of dogs and cats that were diagnosed with urinary tract infection caused by C. urealyticum. RESULTS: This report concerns a total of 11 dogs and 10 cats. All cats had a history of urethral catheterisation, and six cats had undergone urological surgery before diagnosis of this specific infection. Dogs had history of neurogenic urinary incontinence (n=5), urethral catheterisation (n=4), urological surgery (n=4), lower urinary tract disease (n=2) or prostatic disease (n=1). In seven animals, previous urine culture was negative. Median urine pH was 8.6 (interquartile range 7.5 to 9), and 19 animals had pyuria and struvite crystalluria. Encrusted cystitis was diagnosed by abdominal ultrasound in nine animals. All but one isolate were resistant to at least three antimicrobial classes. Thirteen isolates were sensitive to tetracyclines. There was bacterial and clinical resolution of the infection in nine dogs and seven cats. Two animals died from sepsis and two cats were euthanased because of clinical deterioration. CLINICAL SIGNIFICANCE: Urinary tract infection caused by C. urealyticum should be suspected in animals with pre-existing urinary disorders, especially if urine is alkaline and there is struvite crystalluria, negative routine urine culture and encrusted cystitis.

Treatment of inflammatory rectal strictures by digital bougienage: a retrospective study of nine cases.

OBJECTIVES: Inflammatory rectal strictures in dogs and cats have been rarely reported. The aim of this study was to describe nine cases and their treatment by digital bougienage. METHODS: Medical records of dogs and cats referred for constipation, dyschezia or tenesmus and diagnosed with an inflammatory rectal stricture were obtained from the database of two referral centres between 2007 and 2014 and reviewed. RESULTS: Four dogs and five cats met the inclusion criteria. Four of the five cats were purebred kittens. Three cats and two dogs had a history of diarrhoea and two dogs had a history of bone ingestion. Digital rectal examination revealed rectal strictures in all cases. Histopathology revealed a lymphoplasmacytic infiltration in all four dogs and in two cats. All cases were treated by digital bougienage. A psyllium-enriched diet was prescribed in all cats and in two dogs. A complete resolution of clinical signs was reported in all eight cases for which follow-up information was available. CLINICAL SIGNIFICANCE: Benign rectal strictures associated with gastrointestinal inflammation should be routinely included in the differential diagnosis of constipation, tenesmus and dyschezia, especially after an episode of acute or chronic diarrhoea. The treatment described here is simple, minimally invasive and effective in the long term.

Pulmonary vascular dysfunction in end-stage cystic fibrosis: role of NF-kappaB and endothelin-1.

Pulmonary hypertension is rare in chronic respiratory diseases but has a strong impact on the prognosis and is partly underlined by factors other than hypoxaemia. The aim of the present study was to assess the potential role of endothelin-1 (ET-1) and nuclear factor (NF)-kappaB vasoconstrictive pathways in pulmonary hypertension. The effects of ET-1 receptors blockers (BQ 123 and 788) and of genistein were assessed on response to acetylcholine of pulmonary vascular rings from cystic fibrosis (CF) lung transplant recipients (n = 23). NF-kappaB and ET-1 receptor expression was immunodetected in pulmonary arteries and quantitated using Western blotting. ET-1 vascular content was quantitated using ELISA. In total, 14 out of 23 subjects exhibited strongly impaired pulmonary vasodilation (p<0.01 versus nine out of 23 subjects with a normal response) associated with an activation of ET-1 receptors A and NF-kappaB pathways. Genistein restored vasodilation in subjects with an abnormal response. Pulmonary vascular dysfunction is frequent in end-stage CF, involving the NF-kappaB pathway and that of ET-1 through ET-1 receptor A (ETAR). These data leave a conceptual place for ETAR blockers and isoflavones in the management of the devastating vascular complication of chronic obstructive respiratory diseases such as CF.

Quantitative evaluation of renal function in healthy Beagle puppies and mature dogs.

Daily urinary collection and assessment of glomerular filtration rate (GFR) and effective renal plasma flow were performed in ten 2-month-old Beagle puppies and ten 6-9 year-old Beagle dogs to identify age-associated differences in renal function. The most striking differences in puppies compared to mature dogs were a higher daily urinary volume (+65%), GFR (+87%), free water reabsorption (+159%), a lower daily protein excretion (-88%), and fractional excretion of phosphorus (-35%). Renal function in Beagle puppies, but not mature dogs, was also quite different compared to data published in younger adult dogs.

[Endothelial vasoactive factors: predictive markers of the results of the Fontan intervention?]. / Facteurs vasoactifs endothéliaux: marqueurs prédictifs du résultat de l'intervention de Fontan?

UNLABELLED: We retrospectively analyzed the pulmonary biopsies of a Fontan intervention in order to identify predictive markers of its result. The pulmonary biopsies of 17 patients who benefited from the Fontan intervention and 6 controls were studied. The histomorphometric measurements and endothelial expression of vasoactive factors (NO synthase, endothelin-1) and angiogenic factors (VEGF) were analyzed with immunohistochemistry at the level of intra-acini pulmonary arterioles. Eight patients presented a good surgical result (group 1). Distal arterioles presented a thin and regular wall: the NO synthase, endothelin and VEGF expression was low. Nine patients presented a failure of the Fontan operation (group 2). The distal arterioles were slightly musculated (p<0.01 vs. group 1 and group control). The endothelin-1 expression was comparable to that observed in group 1. Conversely, the NO synthase and VEGF expressions were significantly increased in that group (<0.001 vs. group 1 and group control). CONCLUSION: In case of Fontan operation failure, the histological modifications are subtle with a muscular extension of the distal pulmonary arterioles wall. Conversely, a marked increase of NO synthase and VEGF expression is observed which can witness of an endothelial dysfunction. This study could be able to define predictive factors of the evolution and refine the selection of patients candidate for a Fontan operation.

Short-term efficiency and safety of gene delivery into canine kidneys.

BACKGROUND: Gene delivery of biologically active molecules to the kidney may have potential therapeutic applications in renal and cardiovascular diseases. Recombinant adenovirus is one of the most efficient vectors for in vivo gene delivery. However, in vivo toxicity at the site of administration has to be evaluated for the successful use of adenovirus-mediated gene transfer. The aim of this study was to document precisely the short-term safety of different routes of intra-renal adenoviral administration and to compare their transduction efficiency. METHODS: Dog puppies were injected with an adenoviral vector expressing the beta-galactosidase reporter gene in both kidneys via three different routes, i.e. intra-renal-ureteral route (IU) and intra-renal-arterial route with (IAC) or without (IA) clamping of the renal vein. Toxicity of viral administration was assayed on day 4 at both physiological and histological levels. Renal samples were monitored for the presence of nuclear beta-galactosidase-expressing cells. RESULTS: All renal physiological parameters (glomerular filtration rate, effective renal plasma flow, and electrolyte excretion fractions) remained stable whatever the route of viral administration. No histological lesion was detected in any of the haematoxylin-eosin-stained kidney sections, and there was no evidence of ischaemia-reperfusion injury in the kidneys subjected to venous clamping. Efficient transgene expression was obtained in dog kidneys following IAC and IU injection of adenoviral vectors. Gene transfer via the IAC route induced gene expression predominantly in the cortical interstitial cells. Retrograde IU adenoviral injection resulted in reduced transduction efficiency compared with the IAC route, with transgene expression occurring mainly in the distal tubular and pyelic epithelial cells. CONCLUSIONS: The two major findings of this study were (i) the absence of acute histological and functional renal alteration following intra-arterial and intra-ureteral injections of adenoviral vectors in both kidneys of healthy dogs, and (ii) the efficiency of transgene expression with specific cellular targeting according to the route of administration.