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.

ACVIM consensus update on Lyme borreliosis in dogs and cats.

An update of the 2006 American College of Veterinary Internal Medicine (ACVIM) Small Animal Consensus Statement on Lyme Disease in Dogs: Diagnosis, Treatment, and Prevention was presented at the 2016 ACVIM Forum in Denver, CO, followed by panel and audience discussion and a drafted consensus statement distributed online to diplomates for comment. The updated consensus statement is presented below. The consensus statement aims to provide guidance on the diagnosis, treatment, and prevention of Lyme borreliosis in dogs and cats.

Focal Segmental Glomerulosclerosis in Related Miniature Schnauzer Dogs.

Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs in particular. This study describes the morphologic features present in the kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS, characterized by solidification of portions of the capillary tuft, affected 32% to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in older dogs. Seven of 8 dogs had arteriolar hyalinosis. Ultrastructurally, all dogs had evidence of a podocytopathy in the absence of electron-dense deposits, glomerular basement membrane splitting, or fibrils. All dogs had multifocal to extensive podocyte foot process effacement. Other podocyte changes included microvillous transformation, the presence of vacuoles or protein resorption droplets, cytoplasmic electron-dense aggregates, and occasional binucleation. Variable amounts of intraglomerular lipid were present in all dogs. All dogs were proteinuric, with measured values for the urine protein-to-creatinine ratio ranging from 1.2 to 6.5. Azotemia was mild to absent and dogs were euthanatized at 5.1 to 14 years of age, in all cases due to nonrenal diseases. The underlying cause of FSGS in these Miniature Schnauzer dogs has yet to be determined, but contributors likely include genetic podocytopathy, lipid abnormalities, and glomerular hypertension.

Clinical features of hypoadrenocorticism in soft-coated wheaten terrier dogs: 82 cases (1979-2013).

The objective of this retrospective case series, which included 82 client-owned soft-coated wheaten terriers, was to characterize clinical features of hypoadrenocorticism in this breed. Median age at diagnosis was 3.5 years. There was no gender predilection. Clinicopathologic findings included sodium/potassium ratio < 27 (85%), hyperkalemia (76%), hyponatremia (63%), elevated blood urea nitrogen (83%) or creatinine (71%), and hypercalcemia (36%). Nine dogs with normal sodium and potassium (11%) were older and less often azotemic, hyperphosphatemic, or hypercalcemic. Twenty-one dogs (26%) developed protein-losing nephropathy (n = 18) and/or end-stage renal disease (n = 3). Overall median survival time was 5.4 years, but was shorter in dogs with normal sodium and potassium at diagnosis (4.2 years), or those with subsequent protein-losing nephropathy (4.2 years). This population showed no gender predilection, unlike that reported in the general canine population with hypoadrenocorticism, and more comorbid protein-losing nephropathy than in the general soft-coated wheaten terrier population.

Caractéristiques cliniques de l'hypoadrénocorticisme chez les chiens Terrier irlandais à poil doux : 82 cas (1979­2013). L'objectif de cette série de cas rétrospectifs, qui incluait 82 Terriers irlandais à poil doux appartenant à des clients, consistait à déterminer les caractéristiques cliniques de l'hypoadrénocorticisme chez cette race. L'âge moyen du diagnostic était de 3,5 ans. Il n'y avait pas de prédilection selon le sexe. Les résultats clinicopathologiques incluaient le ratio sodium-potassium < 27 (85 %), l'hyperkaliémie (76 %), l'hyponatrémie (63 %), un taux élevé d'azote uréique du sang (83 %) ou de la créatinine (71 %) et l'hypercalcémie (36 %). Neuf chiens avec un taux de sodium et de potassium normal (11 %) étaient âgés et étaient moins souvent azotémiques, hyperphosphatémiques ou hypercalcémiques. Vingt-et-un chiens (26 %) ont développé la néphropathie avec perte de protéines (n = 18) et/ou la maladie rénale en phase terminale (n = 3). Le temps de survie global moyen était de 5,4 ans, mais il était écourté chez les chiens avec un taux normal de sodium et de potassium au moment du diagnostic (4,2 ans) ou chez ceux atteints subséquemment de néphropathie avec perte de protéines (4,2 ans). Cette population n'a pas présenté de prédilection selon le sexe, contrairement à ce qui avait été signalé dans l'ensemble de la population canine atteinte d'hypoadrénocorticisme, et elle affichait une hausse de néphropathie concomitante avec perte de protéines par rapport à la population générale des Terriers irlandais à poil doux.(Traduit par Isabelle Vallières).

Clinicopathologic and atypical features of naturally occurring leptospirosis in dogs: 51 cases (2000-2010).

OBJECTIVE: To determine clinicopathologic features, percentage of atypical abnormalities, antibody titers against Leptospira serogroups, and importance of convalescent titers in dogs with leptospirosis. DESIGN: Retrospective case series. ANIMALS: 51 dogs with leptospirosis. PROCEDURES: Criteria for inclusion were at least 1 positive microscopic agglutination test (MAT) result (titer ≥ 1:1,600 in vaccinated dogs, titer ≥ 1:800 in nonvaccinated dogs, or ≥ 4-fold increase in convalescent titer), a complete medical record (including leptospirosis vaccination date, reason for initial evaluation, and CBC, serum biochemical analysis, and urinalysis results), and clinical signs or laboratory findings consistent with leptospirosis. RESULTS: Initial clinical signs, temporal distribution, and signalment were similar to previous reports. Convalescent MAT titers were necessary for diagnosis in 45% of cases. Atypical abnormalities included radiographic evidence of pulmonary disease in 10 of 23 dogs and hepatic involvement alone in 7 of 51 dogs. Other abnormalities included proteinuria in 34 of 51 dogs, thrombocytopenia in 26 of 51, coagulopathy in 7 of 24 dogs, hypoalbuminemia in 14 of 51 dogs, and glucosuria in 9 of 51 dogs. Significant associations were found between antibodies against serogroup Grippotyphosa and renal involvement and serogroup Icterohaemorrhagiae and hepatic involvement. CONCLUSIONS AND CLINICAL RELEVANCE: Increased awareness of atypical abnormalities may decrease misdiagnosis of leptospirosis in dogs. Results of concurrent infectious disease testing should be interpreted with caution; misdiagnosis of leptospirosis could pose a public health risk. Convalescent titers were necessary to identify infection when acute testing results were negative. Further research is needed to determine the true associations between antibodies against identified serogroups and clinical features.

Lyme nephritis.

OBJECTIVE: To review what is known and highlight knowledge gaps regarding Lyme nephritis (LN). DATA SOURCES: Publications identified via PubMed using the keywords "Borrelia burgdorferi," "Borreliosis," "glomerulonephritis," "protein-losing nephropathy," "autoimmunity," and "retriever," and as generated by investigators working in the fields of Borreliosis and immune-mediated glomerulonephritis. HUMAN DATA SYNTHESIS: Postborrelial immune-mediated glomerulonephritis was described recently in 6 people; 3 responded to antimicrobials/steroids, 1 to antimicrobials/angiotensin-converting enzyme inhibitor/warfarin, 1 required hemodialysis but became hemodialysis independent after 5 months and treatment with antimicrobials, steroids, plasmapheresis, immunoglobulin, and 1 did not respond to steroids and angiotensin-converting enzyme inhibitor and still requires hemodialysis. VETERINARY DATA SYNTHESIS: Lyme nephritis is seen in <1-2% of Lyme seropositive dogs, with an average onset at 5-6 years. Labrador and Golden Retrievers are predisposed to this condition. Prior or concurrent lameness is described in 9-28% cases. Historical presentations include acute progressive protein-losing nephropathy with membranoproliferative glomerulonephritis, tubular necrosis/regeneration, and interstitial nephritis, but possibly milder forms exist. Complications include thromboembolic events, hypertension, effusive disease, and oliguric/anuric renal failure. Diagnostic tests help stage disease and rule out other causes. Renal biopsy is advocated early, when intervention may help, and to prove if immune-complex disease exists. Treatment includes standard therapy for protein-losing nephropathy, long-term antimicrobials, and perhaps immunosuppressive therapy. CONCLUSIONS: There is no experimental model of LN to study predisposing factors, pathogenesis, onset, progression, treatment, or prevention. There are no predictive tests to identify the few individuals at highest risk, therefore all seropositive dogs should be screened and monitored for proteinuria. Lyme nephritis mimics other forms of protein-losing nephropathy and sometimes Leptospirosis. Renal biopsy helps show if immune-complex disease exists, but may not prove LN specifically. More studies are warranted on dogs with Lyme-specific immune-complex deposition to evaluate risk factors, understand pathogenesis, variability of expression, and to validate treatment and prevention protocols.

Familial renal disease in soft-coated wheaten terriers.

OBJECTIVE: To review what is known about the familial renal diseases in soft-coated wheaten terriers (SCWT), provide an update in developments in this field including the relationship with protein-losing nephropathy (PLN) and the potential association with protein-losing enteropathy (PLE). DATA SOURCES: Information was derived from studies of dogs maintained in the North Carolina State University colony, information contained within an open registry of affected dogs, and data gathered from the general population of wheaten terriers at risk as well as studies performed on banked DNA samples from affected SCWT in the general population and normal geriatric dogs seen at the University of Pennsylvania (PennVet). HUMAN DATA SYNTHESIS: A two-hit pathogenesis has been proposed in some types of human focal segmental glomerulosclerosis, specifically the subset of cases that are associated with a podocytopathy. At risk podocytes may be predisposed to injury by disease processes that would be reversible in other patients. VETERINARY DATA SYNTHESIS: Mutations were found in association with PLN in SCWT, indicating a podocytopathy that causes a change in glomerular permselectivity. This podocytopathy leads to the development of lesions resembling focal segmental glomerulosclerosis. There is also strong evidence supporting a high prevalence of food hypersensitivity reactions in SCWT, although it is unclear if these reactions have a primary or secondary role in the development of PLE. There are also suggestions of immunodysregulation in affected SCWT. CONCLUSIONS: PLN in SCWT is due to a podocytopathy. The cause of PLE has not been identified; however, it is possible that PLE develops from a functional-structural abnormality in the intestines and food allergies develop as secondary phenomena. It is also possible that inflammatory events that are the result of either immunodysregulation or food allergies might lead to the development of PLE. In either case, PLE most likely exacerbates PLN in affected SCWT.

MHC class II association study in eight breeds of dog with hypoadrenocorticism.

Canine hypoadrenocorticism is an endocrine disorder characterised by inadequate secretion of steroid hormones from the adrenal glands. Pathology results from immune-mediated destruction of the adrenal cortex, which is similar to that seen in the human Addison's disease. Both the canine and human diseases have similar clinical presentation, with the diagnosis based on performing a dynamic adrenocorticotropic hormone stimulation test. MHC class II has previously been associated with the human and canine diseases. In the current study, we conducted an MHC class II association study in eight breeds of dog with diagnoses of hypoadrenocorticism. We demonstrated significant differences in dog leukocyte antigen (DLA) haplotype frequencies in six of these breeds: Cocker spaniel, Springer spaniel, Labrador, West Highland white terrier (WHWT), Bearded collie, and Standard poodle. In the Springer spaniel, the DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01 haplotype was significantly associated with disease risk (p = 0.014, odds ratio (OR) = 5.14) and showed a similar trend in the Cocker spaniel. This haplotype is related to one associated with hypoadrenocorticism in the Nova Scotia duck tolling retriever. Similar haplotypes shared between breeds were demonstrated, with DLA-DRB1*001:01--DQA1*001:01--DQB1*002:01 more prevalent in both affected Labrador (p = 0.0002, OR = 3.06) and WHWT (p = 0.01, OR = 2.11). Other haplotypes that have not previously been associated with the disease were identified. The inter-breed differences in DLA haplotypes associated with susceptibility to canine hypoadrenocorticism could represent divergent aetiologies. This could have implications for clinical diagnosis and future comparative studies. Alternatively, it may suggest that the gene of interest is closely linked to the MHC.

Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft-coated Wheaten Terrier dogs.

Dogs of the soft-coated wheaten terrier breed (SCWT) are predisposed to adult-onset, genetically complex, protein-losing nephropathy (average onset age = 6.3 ± 2.0 years). A genome-wide association study using 62 dogs revealed a chromosomal region containing three statistically significant SNPs (p(raw) ≤ 4.13 × 10(-8); p(genome) ≤ 0.005) when comparing DNA samples from affected and geriatric (≥14 years) unaffected SCWTs. Sequencing of candidate genes in the region revealed single nucleotide changes in each of two closely linked genes, NPHS1 and KIRREL2, which encode the slit diaphragm proteins nephrin and Neph3/filtrin, respectively. In humans, mutations in nephrin and decreased expression of Neph3 are associated with podocytopathy and protein-losing nephropathy. The base substitutions change a glycine to arginine in the fibronectin type 3 domain of nephrin and a proline to arginine in a conserved proline-rich region in Neph3. These novel mutations are not described in other species, nor were they found in 550 dogs of 105 other breeds, except in 3 dogs, including an affected Airedale terrier, homozygous for both substitutions. Risk for nephropathy is highest in dogs homozygous for the mutations (OR = 9.06; 95 % CI = 4.24-19.35). This is the first molecular characterization of an inherited podocytopathy in dogs and may serve as a model for continued studies of complex genetic and environmental interactions in glomerular disease.

Resolution of a proteinuric nephropathy associated with Babesia gibsoni infection in a dog.

A 4 yr old male castrated Labrador retriever was evaluated for a short history of inappetance, lethargy, small-bowel diarrhea, polyuria, and polydipsia. Clinicopathologic abnormalities were consistent with protein-losing nephropathy and renal azotemia. Expansive infectious disease testing implicated Babesia gibsoni via whole blood polymerase chain reaction. Renal histopathology results were consistent with membranoproliferative glomerulonephritis and immune complex deposition. The dog was treated with azithromycin, atovaquone, and one dose of corticosteroids/cyclophosphamide. Three months after therapy was completed, the dog was clinically healthy, and all clinicopathologic abnormalities (including Babesia species polymerase chain reaction) had resolved. Atypical presentations of Babesia gibsoni should be considered with proteinuric nephropathy.

Protein-losing nephropathy in small animals.

Genetic and acquired defects of glomerular permselectivity may lead to proteinuria and protein-losing nephropathy (PLN). Morbidity and mortality from complications of PLN may be severe even before progression to azotemia and renal failure. Leakage of plasma proteins into the glomerular filtrate can damage tubular cells and the function of the entire nephron. Detection, localization, and treatment of proteinuria are important to decrease the clinical signs and complications of PLN and the likelihood of progression to renal failure. Thorough diagnostic work-ups help to identify subsets of glomerular disease and their response to specific treatment protocols.

Presumptive hepatotoxicity and rhabdomyolysis secondary to phenazopyridine toxicity in a dog.

OBJECTIVE: To describe a rare, but potential clinical manifestation of phenazopyridine (PAP) toxicity in a dog. CASE SUMMARY: A 6-year-old spayed female Chihuahua was evaluated for ataxia and dysphagia after ingestion of 200 mg (66 mg/kg) of PAP hydrochloride. The dog was presented to the hospital with shifting leg lameness involving all 4 limbs, which progressed to reluctance to walk and severe diffuse muscle hyperesthesia. Clinical laboratory abnormalities included marked increases in serum alanine aminotransferase, aspartate aminotransferase, creatine kinase, mild increases in alkaline phosphatase, and increased c-Tnl-troponin concentration. Treatment included administration of intravenous fluids, muscle relaxants, pain medications, and hepatoprotectants for 5 days in the hospital, and medical management at home for an additional 5 days. Follow-up examinations performed 1 and 6 months after initial presentation revealed the dog to be clinically healthy with serum biochemical profiles within reference intervals. NEW OR UNIQUE INFORMATION PROVIDED: The purpose of this report is to describe an unusual manifestation of PAP toxicosis in a dog, which has not been previously reported in the literature. A review of the ASPCA Animal Poison Control Center database revealed 347 cases of PAP exposure in dogs during 2000-2009 underscoring the importance of being aware of this toxicity in the dog.

ACVIM small animal consensus statement on Lyme disease in dogs: diagnosis, treatment, and prevention.

The purpose of this report is to offer a consensus opinion of ACVIM diplomates on the diagnosis, treatment, and prevention of Borrelia burgdorferi infections in dogs (canine Lyme disease). Clinical syndromes known to commonly be associated with canine Lyme disease include polyarthritis and glomerulopathy. Serological test results can be used to document exposure to B. burgdorferi but not prove illness. Although serum enzyme-linked immunosorbent assay/indirect fluorescent antibody assay titers can stay positive for months to years after treatment, quantitative C6 peptide antibody paired tests need more study. Serological screening of healthy dogs is controversial because it can lead to overdiagnosis or overtreatment of normal dogs, most of which never develop Lyme disease. However, serological screening can provide seroprevalence and sentinel data and stimulate owner education about tick infections and control. Although it is unknown whether treatment of seropositive healthy dogs is beneficial, the consensus is that seropositive dogs should be evaluated for proteinuria and other coinfections and tick control prescribed. Tick control can include a product that repels or protects against tick attachment, thereby helping to prevent transmission of coinfections as well as Borrelia spp. Seropositive dogs with clinical abnormalities thought to arise from Lyme disease generally are treated with doxycycline (10 mg/kg q24h for 1 month). Proteinuric dogs might need longer treatment as well as medications and diets for protein-losing nephropathy. The ACVIM diplomates believe the use of Lyme vaccines still is controversial and most do not administer them. It is the consensus opinion that additional research is needed to study predictors of illness, "Lyme nephropathy," and coinfections in Lyme endemic areas.

Canine borreliosis.

A guild of organisms carried by the same vector (Ixodes ticks) in Lyme-endemic areas may be confounding the understanding of Lyme disease in dogs. A new diagnostic method, the C6 peptide test for Lyme, and serology and PCR testing for Ehrlichia, Babesia, and Bartonella species will help to sort out seroprevalence and symptomatology caused by exposure to these agents or by coinfections. In addition, Rickettsia, Leptospira, Mycoplasma species, and more could be involved in dogs diagnosed with a "doxycycline-responsive" disease. The author does not recommend treating asymptomatic Borrelia carrier dogs, but does recommend screening them for proteinuria and for exposure to other agents. A positive Lyme titer is a marker of exposure to Ixodes ticks and the agents they carry. The risk/benefit of vaccination will be understood better as the symptomatology and immunopathogenesis of Lyme disease are defined. Meanwhile, tick control is highly recommended for all dogs in Lyme-endemic areas.