ACVIM consensus update on Lyme borreliosis in dogs and cats Littman, Meryl P.; Gerber, Bernhard; Goldstein, Richard E. ...
Journal of veterinary internal medicine,
May/June 2018, Letnik:
32, Številka:
3
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
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.
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.
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.
Lyme nephritis Littman, Meryl P.
Journal of veterinary emergency and critical care (San Antonio, Tex. : 2000),
03/2013, Letnik:
23, Številka:
2
Journal Article
Recenzirano
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.
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.
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.
Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present ...clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immunecomplex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1) glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked), and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive); and 2) glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to nonsynonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic counseling using DNA testing is available for several breeds but many more inherited canine models of glomerulopathy still need to be characterized. Dog breeds, with their long haplotypes and linkage disequilibrium, represent excellent models to study the underlying molecular basis for protein-losing nephropathy, glomerular function, genetic manipulations, possible environmental triggers, and treatments. Results of studies of genetic canine diseases will help dogs and other species, including man. Keywords: Alport, glomerulosclerosis, glomerulonephritis, nephrin, NPHS1, podocytopathy
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.
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.
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.
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