Pseudohypoaldosteronism and acquired renal aldosterone resistance with hyperkalemic type IV renal tubular acidosis in 2 cats.

This report describes the diagnosis and treatment of aldosterone resistance (AR) and acquired hyperkalemic type IV renal tubular acidosis (RTA) in 2 cats comparable to acquired pseudohypoaldosteronism in people. One cat developed AR from chronic kidney disease after an acute kidney injury and was treated with furosemide per os, which resolved the hyperkalemic RTA. The second cat developed transient AR secondary to a bacterial urinary tract infection associated with urethral catheterization, and treatment with antibiotics resolved the hyperkalemic RTA.

International renal interest society best practice consensus guidelines for intermittent hemodialysis in dogs and cats.

Intermittent hemodialysis (IHD) is an advanced adjunctive standard of care for severe acute kidney injury (AKI) and other indications. Most animals with AKI are managed medically, however, when the disease is severe, medical management may not control the consequences of the disease, and animals with a potential for renal recovery may die from the consequences of uremia before recovery has occurred. Extracorporeal therapies aid the management of AKI by expanding the window of opportunity for recovery of sufficient kidney function to become dialysis independent. Intermittent hemodialysis (IHD) was introduced into veterinary medicine over 50 years ago, however, updated guidelines for the delivery of IHD have not been published for several decades. To that end, the International Renal Interest Society (IRIS) constituted a Working Group to establish best practice guidelines for the safe and effective delivery of IHD to animals with indications for dialytic intervention. The IRIS Working Group generated 60 consensus statements and supporting rational for a spectrum of prescription and management categories required for delivery of IHD on designated intermittent dialysis platforms (i.e., AKI, chronic hemodialysis and intoxications). A formal consensus method was used to validate the recommendations by a blinded jury of 12 veterinarians considered experts in extracorporeal therapies and actively performing IHD. Each vote provided a level of agreement for each recommendation proposed by the Working Group. To achieve a consensus, a minimum of 75% of the voting participants had to "strongly agree" or "agree" with the recommendation.

International Renal Interest Society best practice consensus guidelines for the diagnosis and management of acute kidney injury in cats and dogs.

Acute kidney injury (AKI) is defined as an injury to the renal parenchyma, with or without a decrease in kidney function, as reflected by accumulation of uremic toxins or altered urine production (i.e., increased or decreased). AKI might result from any of several factors, including ischemia, inflammation, nephrotoxins, and infectious diseases. AKI can be community- or hospital-acquired. The latter was not previously considered a common cause for AKI in animals; however, recent evidence suggests that the prevalence of hospital-acquired AKI is increasing in veterinary medicine. This is likely due to a combination of increased recognition and awareness of AKI, as well as increased treatment intensity (e.g., ventilation and prolonged hospitalization) in some veterinary patients and increased management of geriatric veterinary patients with multiple comorbidities. Advancements in the management of AKI, including the increased availability of renal replacement therapies, have been made; however, the overall mortality of animals with AKI remains high. Despite the high prevalence of AKI and the high mortality rate, the body of evidence regarding the diagnosis and the management of AKI in veterinary medicine is very limited. Consequently, the International Renal Interest Society (IRIS) constructed a working group to provide guidelines for animals with AKI. Recommendations are based on the available literature and the clinical experience of the members of the working group and reflect consensus of opinion. Fifty statements were generated and were voted on in all aspects of AKI and explanatory text can be found either before or after each statement.

ACVIM consensus statement on diagnosis and management of urinary incontinence in dogs.

Urinary incontinence (UI) is a disorder of micturition that can occur in dogs of any age, sex, and breed depending on the underlying cause and time of onset. Diagnosis and treatment for various causes of UI in dogs have been described by multiple comprehensive single author review articles, but large prospective clinical trials comparing treatment outcomes in veterinary medicine are lacking. The objectives of this consensus statement therefore are to provide guidelines on both recommended diagnostic testing and treatment for various causes of UI in dogs. Specifically, pathophysiology directly related to the canine urinary system will be reviewed and diagnostic and therapeutic challenges will be addressed. A panel of 12 experts in the field (8 small animal internists [L. Adams, J. Bartges, A. Berent, J. Byron, J. Foster, A. Kendall, S. Vaden, J. Westropp], 2 neurologists [J. Coates, N. Olby], 1 radiologist [G. Oetelaar], and 1 surgeon [C. Adin]) was formed to assess and summarize evidence in the peer-reviewed literature and to complement it with consensus recommendations using the Delphi method. Some statements were not voted on by all panelists. This consensus statement aims to provide guidance for management of both male and female dogs with underlying storage or voiding disorders resulting in UI.

Adeno-associated virus-vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease.

BACKGROUND: A treatment of chronic kidney disease (CKD)-associated anemia in cats is needed. SB-001 is an adeno-associated virus-vectored (AAV)-based gene therapeutic agent that is administered intramuscularly, causing the expression of feline erythropoietin. HYPOTHESIS/OBJECTIVE: We hypothesized that SB-001 injection would lead to a sustained increase in PCV in cats with CKD-associated anemia. ANIMALS: Twenty-three cats with International Renal Interest Society (IRIS) Stage 2 to 4 CKD-associated anemia were enrolled at 4 veterinary clinics. METHODS: In a prospective clinical trial, cats were treated with 1 of 3 regimens of SB-001 (Lo 1.2 × 109 genome copies [GCs] on Day 0; Lo ± Hi [supplemental 2nd dose of 3.65 × 109 GC on Day 42]; Hi 3.65 × 109 GC IM on Day 0) and followed for 70 days. RESULTS: A response to SB-001 at any time between Day 28 and Day 70 was seen in 86% (95% confidence interval 65, 97%) of all cats. There was a significant (P < .003) increase in PCV from Day 0 to Day 28 (mean increase 6 ± 6 percentage points [pp]; n = 21), Day 42 (8 ± 9 pp; n = 21), Day 56 (10 ± 11 pp; n = 17), and Day 70 (13 ± 14 pp, n = 14). Twelve cats were hypertensive at baseline, 4 of which developed encephalopathy during the study. An additional 6 cats became hypertensive during the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Results of this study suggest that SB-001 therapy represents a suitable single injection treatment that can address nonregenerative anemia in cats with CKD. It was generally well tolerated; however, hypertension and encephalopathy developed in some cats as previously described in association with erythropoiesis-stimulating agent therapy.

Population pharmacokinetic analysis of enrofloxacin and its active metabolite ciprofloxacin after intravenous injection to cats with reduced kidney function.

BACKGROUND: It is unknown if enrofloxacin accumulates in plasma of cats with reduced kidney function. HYPOTHESIS: To determine if enrofloxacin and its active metabolite ciprofloxacin have reduced clearance in azotemic cats. ANIMALS: Thirty-four cats hospitalized for clinical illness with variable degree of kidney function. METHODS: Prospective study. After enrofloxacin (dose 5 mg/kg) administration to cats, sparse blood sampling was used to obtain 2 compartment population pharmacokinetic results using nonlinear mixed-effects modeling. Plasma enrofloxacin and ciprofloxacin concentrations were measured and summed to obtain the total fluoroquinolone concentration. A model of ciprofloxacin metabolism from enrofloxacin was created and evaluated for covariate effects on clearance, volume of distribution, and the metabolic rate of ciprofloxacin generation from enrofloxacin. RESULTS: Body weight was the only covariate found to affect total fluoroquinolone volume of distribution (effect 1.63, SE 0.19, P < .01) and clearance (effect 1.63, SE 0.27, P < .01). Kidney function did not have a significant effect on total fluoroquinolone clearance (median 440.8 mL/kg/h (range 191.4-538.0 mL/kg/h) in cats with normal kidney function, 365.8 mL/kg/h (range 89.49-1092.0 mL/kg/h) in cats with moderate kidney dysfunction, and 308.5 mL/kg/h (range 140.20-480.0 mL/kg/h) in cats with severe kidney dysfunction (P = .64). Blood urea nitrogen concentration influenced the metabolic generation of ciprofloxacin from enrofloxacin (effect 0.51, SE 0.08, P < .01), but other markers of kidney function did not. CONCLUSIONS AND CLINICAL IMPORTANCE: Adjustment of enrofloxacin dosage is not indicated for azotemic cats.

Multiple variants in XDH and MOCOS underlie xanthine urolithiasis in dogs.

Hereditary xanthinuria is a rare autosomal recessive disease caused by missense and loss of function variants in the xanthine dehydrogenase (XDH) or molybdenum cofactor sulfurase (MOCOS) genes. The aim of this study was to uncover variants underlying risk for xanthinuria in dogs. Affected dogs included two Manchester Terriers, three Cavalier King Charles Spaniels, an English Cocker Spaniel, a Dachshund, and a mixed-breed dog. Four putative causal variants were discovered: an XDH c.654G > A splice site variant that results in skipping of exon 8 (mixed-breed dog), a MOCOS c.232G > T splice site variant that results in skipping of exon 2 (Manchester Terriers), a MOCOS p.Leu46Pro missense variant (Dachshund), and a MOCOS p.Ala128Glyfs*30 frameshift variant that results in a premature stop codon (Cavalier King Charles Spaniels and English Cocker Spaniel). The two splice site variants suggest that the regions skipped are critical to the respective enzyme function, though protein misfolding is an alternative theory for loss of function. The MOCOS p.Leu46Pro variant has not been previously reported in human or other animal cases and provides novel data supporting this residue as critical to MOCOS function. All variants were present in the homozygous state in affected dogs, indicating an autosomal recessive mode of inheritance. Allele frequencies of these variants in breed-specific populations ranged from 0 to 0.18. In conclusion, multiple diverse variants appear to be responsible for hereditary xanthinuria in dogs.

Urine cortisol-creatinine and protein-creatinine ratios in urine samples from healthy dogs collected at home and in hospital.

BACKGROUND: Recently, urine protein:creatinine ratios (UPC) were shown to be lower in urine samples from dogs collected at home (AH) as compared to those collected in hospital (IH). Stress-inducing procedures and travel to the hospital have been hypothesized to cause prerenal proteinuria. OBJECTIVES: Evaluate patient stress using urine cortisol:creatinine ratios (UCCr) and correlate UCCr to UPC in urine samples obtained AH and IH. ANIMALS: Thirty-six healthy, client-owned dogs. METHODS: Prospective, non-masked study. Two voided urine samples were obtained (AH and IH). Complete urinalysis as well as UPC and UCCr were performed. Clients graded their dogs' stress level AH, in transport, and IH. RESULTS: The UCCr was significantly higher in IH samples than in AH samples (P < .0001), but UPC was not significantly different between AH and IH urine samples (P = .14). In all samples and in both collection settings, UCCr was not significantly correlated with UPC. Travel time and time IH were not correlated with change in UCCr or UPC. In 8 dogs with borderline or overt proteinuria, no significant difference was found in UPC between settings, but UCCr was significantly higher in IH samples. CONCLUSIONS AND CLINICAL IMPORTANCE: The UPC was not higher when measured in urine samples collected IH compared to AH. Dogs had higher UCCr IH, but UCCr was not associated with UPC. Stress, as estimated by UCCr, did not affect proteinuria. Further evidence is needed to support the claim that stress may result in proteinuria in healthy dogs.

Complications and clinical utility of ultrasonographically guided pyelocentesis and antegrade pyelography in cats and dogs: 49 cases (2007-2015).

OBJECTIVE: To describe the diagnostic utility and clinical safety of ultrasonographically guided percutaneous pyelocentesis and antegrade pyelography in cats and dogs. DESIGN: Retrospective case series. ANIMALS: 39 cats and 10 dogs with 55 affected kidneys. PROCEDURES: Medical records were reviewed to identify cats and dogs that underwent ultrasonographically guided pyelocentesis and antegrade pyelography between June 1, 2007, and December 31, 2015. Data collected included procedure descriptions; results of diagnostic imaging, urine cytologic evaluation, and bacterial culture; and evidence of complications. Animals were assigned to the pyelocentesis group (underwent only pyelocentesis) or to the antegrade pyelography group (underwent pyelocentesis followed immediately by pyelography). RESULTS: The diagnostic rate for pyelography was 94% (31/33; 95% confidence interval [CI], 80.4% to 98.9%). The total, minor, and major complication rates for both treatment groups combined were 25% (95% CI, 15.8% to 38.3%), 24% (95% CI, 14.4% to 36.3%), and 2% (95% CI, 0.09% to 9.6%), respectively. Performing bacterial culture of urine obtained by pyelocentesis did not provide an advantage over performing bacterial culture of urine obtained from the lower urinary tract. CONCLUSIONS AND CLINICAL RELEVANCE: Findings indicated that ultrasonographically guided pyelocentesis and antegrade pyelography were well-tolerated techniques for investigating upper urinary tract disease in cats and dogs and that pyelography had a higher diagnostic rate than previously reported; therefore, pyelography should be considered for identification of mechanical and functional ureteral patency abnormalities in cats and dogs.

Characterization of subclinical bacteriuria, bacterial cystitis, and pyelonephritis in dogs with chronic kidney disease.

OBJECTIVE To determine the prevalence of bacteriuria (ie, a positive microbial culture result for ≥ 1 urine sample) in dogs with chronic kidney disease (CKD) and characterize findings of subclinical bacteriuria (SBU), bacterial cystitis, or pyelonephritis in these patients. DESIGN Retrospective, observational study. ANIMALS 182 dogs. PROCEDURES Medical records from January 2010 through July 2015 were reviewed to identify dogs with CKD that underwent urinalysis and urine microbial culture. Signalment, clinicopathologic data, stage of CKD according to previously published guidelines, results of urinalysis and urine culture, and abdominal ultrasonographic findings were recorded. Dogs with positive urine culture results were categorized as having SBU, bacterial cystitis, or pyelonephritis on the basis of these data. Prevalence of bacteriuria was calculated. Associations between CKD stage, presence of bacteriuria, and diagnosis category were analyzed statistically. RESULTS 33 of 182 (18.1%) dogs (40/235 [17.0%] urine samples) had positive culture results. All dogs received antimicrobials on the basis of culture and susceptibility test findings. Most positive culture results (18/40 [45%] samples) were found for dogs with SBU, followed by dogs with pyelonephritis (16/40 [40%]) and cystitis (6/40 [15%]). Escherichia coli was the most frequently observed isolate (29/40 [73%] cultures from 25/33 dogs). The CKD stage was not associated with presence of bacteriuria or diagnosis category. CONCLUSIONS AND CLINICAL RELEVANCE The prevalence of positive urine culture results in dogs with CKD was lower than that reported for dogs with some systemic diseases that may predispose to infection. Prospective research is needed to assess the clinical importance of SBU in dogs with CKD.

Associations between dialysate sodium concentration and plasma sodium concentration of dogs receiving intermittent hemodialysis treatments.

OBJECTIVE To compare dialysate sodium concentration and patient plasma sodium concentration of dogs during intermittent hemodialysis treatments. SAMPLE 211 intermittent hemodialysis treatments performed on 40 client-owned dogs for the management of dialysis-dependent uremia. PROCEDURES Medical records were reviewed to determine the plasma sodium concentration of each dog before and after routine hemodialysis treatments. Associations between detected changes in plasma sodium concentration and dialysate sodium concentration were evaluated by use of Spearman rank correlations and linear regression analysis. RESULTS Significant linear correlations were found between the dialysate sodium concentration and patient sodium concentration. The starting dialysate-to-patient sodium gradient was associated with the strongest correlation to the change in patient sodium concentration at the end of the dialysis session. Modest correlations existed between the dialysate sodium concentration and postdialysis patient sodium concentration as well as between the predialysis dialysate-to-patient sodium gradient and postdialysis dialysate-to-patient sodium gradient. CONCLUSIONS AND CLINICAL RELEVANCE The dialysate sodium concentration was correlated with the patient sodium concentration in dogs, and the dialysate-to-patient sodium gradient could be used to further refine this association to predict the postdialysis patient sodium concentration and potentially manage dysnatremia during hemodialysis. Prospective studies should be performed to determine how these associations can be used to correct aberrations as well as to avoid unwanted alterations in patient sodium concentrations.

Treatment of ibuprofen toxicity with serial charcoal hemoperfusion and hemodialysis in a dog.

OBJECTIVE: To describe the efficacy of serial charcoal hemoperfusion and hemodialysis in removing ibuprofen from a dog with severe clinical signs of toxicity. CASE SUMMARY: A dog ingested a minimum of 2,200 mg/kg of ibuprofen resulting in progressive neurologic dysfunction that progressed to a comatose state by the time of presentation. Extracorporeal charcoal hemoperfusion coupled serially with hemodialysis was performed to remove ibuprofen from this patient. Serial charcoal hemoperfusion and hemodialysis therapy resulted in complete reversal of the neurologic dysfunction in this dog. No evidence of acute kidney or hepatic injury was observed. Serum ibuprofen concentrations confirmed the efficacy of this treatment. NEW INFORMATION PROVIDED: This report details the technique for extracorporeal extraction of ibuprofen, a methodology that could be employed for other toxicities due to substances with similar pharmacokinetics. Complications and limitations (eg, saturation of the charcoal cartridge) of the therapy are discussed.

Update on Mineral and Bone Disorders in Chronic Kidney Disease.

The inappropriate phosphorus retention observed in chronic kidney disease is central to the pathophysiology of mineral and bone disorders observed in these patients. Subsequent derangements in serum fibroblast growth factor 23, parathyroid hormone, and calcitriol concentrations play contributory roles. Therapeutic intervention involves dietary phosphorus restriction and intestinal phosphate binders in order to correct phosphorus retention and maintain normocalcemia. Additional therapies may be considered to normalize serum fibroblast growth factor 23 and parathyroid hormone.

Proliferative, necrotizing and crescentic immune complex-mediated glomerulonephritis in a cat.

CASE SUMMARY: A 5-year-old cat was examined for vomiting and anorexia of 2 days' duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main biochemical findings. Serial analyses of the urine revealed isosthenuria, proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected surrounding the right kidney by ultrasonography. Histopathologic evaluation of ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent with proliferative, necrotizing and crescentic glomerulonephritis with fibrin thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic-active interstitial nephritis. Owing to a lack of clinical improvement, the cat was eventually euthanized. Post-mortem renal biopsies were processed for light microscopy, transmission electron microscopy and immunofluorescence. This revealed severe focal proliferative and necrotizing glomerulonephritis with cellular crescent formation, podocyte injury and secondary segmental sclerosis. Ultrastructural analysis revealed scattered electron-dense deposits in the mesangium, and immunofluorescence demonstrated positive granular staining for λ light chains, consistent with immune complex-mediated glomerulonephritis. Severe diffuse acute tubular epithelial injury and numerous red blood cell casts were also seen. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of naturally occurring proliferative, necrotizing and crescentic immune complex glomerulonephritis in a cat.

Endoscopy-guided ectopic egg removal from the urinary bladder in a leopard tortoise (Stigmochelys pardalis).

Egg retention in the urinary bladder of a leopard tortoise was diagnosed by radiography and confirmed by cystoscopy. The egg was removed with a modified polypectomy snare, aided by a flexible endoscope and insufflation. No complications occurred during the procedures and the tortoise made a complete recovery.

Excision par endoscopie guidée d'un œuf ectopique de la vessie urinaire d'une tortue-panthère(Stigmochelys pardalis). La rétention des œufs dans la vessie urinaire d'une tortue-panthère a été diagnostiquée par radiographie et confirmée par cystoscopie. L'œuf a été excisé avec une anse de polypectomie modifiée à l'aide d'un endoscope flexible et d'une insufflation. Aucune complication ne s'est produite durant les interventions et la tortue s'est complètement rétablie.(Traduit par Isabelle Vallières).

Use of linezolid to treat MRSP bacteremia and discospondylitis in a dog.

A 1.5 yr old male German shepherd dog was evaluated for recurrent intermittent episodes of fever and lethargy. Clinicopathologic abnormalities were suggestive of a discospondylitis at the seventh and eighth thoracic vertebrae. Blood and urine cultures yielded growth of methicillin-resistant Staphylococcus pseudintermedius (MRSP) that was resistant to all commonly used antibiotics. Extralabel antibiotic susceptibility testing demonstrated susceptibility of both blood and urine isolates to linezolid. The prescribed dose was extrapolated from pharmacokinetic (PK) studies and the isolate's plasma minimum inhibitory concentration (MIC). Linezolid was administered for 23 wk and resulted in successful resolution of bacteremia, bacteriuria, and discospondylitis. When justified, linezolid should be considered to treat methicillin-resistant infections.

A case of apparent canine erysipeloid associated with Erysipelothrix rhusiopathiae bacteraemia.

BACKGROUND: Erysipelothrix rhusiopathiae is a Gram-positive facultative anaerobe found worldwide and is most commonly associated with skin disease in swine, while anecdotal reports of cases in dogs have been associated with endocarditis. HYPOTHESIS/OBJECTIVES: Clinicians should consider systemic infectious diseases as a potential cause of erythematous skin lesions. ANIMALS: A 5-year-old female spayed Labrador retriever presented with lethargy, anorexia and erythematous skin lesions while receiving immunosuppressive therapy for immune-mediated haemolytic anaemia. Four days prior to presentation, the dog had chewed on a raw turkey carcase. METHODS: Complete blood count, serum chemistry profile, urinalysis and blood cultures. RESULTS: Blood cultures yielded a pure growth of E. rhusiopathiae serotype 1b. Amoxicillin 22 mg/kg orally twice daily for 2 weeks and discontinuation of azathioprine resulted in remission of fever and skin lesions. CONCLUSIONS AND CLINICAL IMPORTANCE: This report is the first documentation, to the best of the authors' knowledge, of Erysipelothrix infection, a known zoonosis, in an immunosuppressed dog, highlighting the need for infectious disease monitoring in patients receiving such therapy. This information may also help educate veterinarians to include Erysipelothrix infection as a differential diagnosis in dogs with fever and skin lesions, as well as the role of blood cultures in diagnosing this disease.

Bilateral ureteropelvic junction stenosis causing hydronephrosis and renal failure in an adult cat.

A 3.5-year-old male neutered cat was presented for investigation of renomegaly appreciated during a routine physical examination. Marked renomegaly due to bilateral hydronephrosis was detected and further testing identified International Renal Interest Society stage 2, non-hypertensive, non-proteinuric chronic kidney disease. Ten months later the cat was evaluated for acute lethargy; severe azotemia with oliguria was documented. Medical therapy failed to result in clinical improvement and the cat was euthanased. Necropsy revealed bilateral marked hydronephrosis secondary to a tortuous proximal ureter consistent with proximal ureteropelvic junction stenosis. This is the first report of this disorder leading to progressive renal failure in a cat.