A comparative study of chronic kidney disease in dogs and cats: induction of cyclooxygenases

The present study investigated whether renal cyclooxygenase (COX) induction is associated with the severity of chronic kidney disease (CKD) in dogs and cats. The collected kidneys were examined histopathologically and immunohistochemically. The immunoreactivities of COX-1 and COX-2 were evaluated quantitatively, and the correlations to the plasma creatinine concentrations, glomerular size, glomerulosclerosis, interstitial fibrosis, and interstitial cell infiltration were evaluated statistically. Immunoreactivities for COX-1 were heterogeneously observed in the medullary distal tubules and collecting ducts; no correlations with the severity of renal damage were detected. Immunoreactivities for COX-2 were heterogeneously observed in the macula densa (MD) regions. In dogs, the percentage of COX-2-positive MD was significantly correlated with the glomerular size. In cats, glomeruli with COX-2-positive MD had significantly higher sclerosis scores than those with COX-2-negative MD. In conclusion, renal COX-2 is induced in canine and feline CKD, especially in relation to the glomerular changes.     

Quantitative analysis of inflammatory and immune responses in dogs with gastritis and their relationship to Helicobacter spp. infection

The present study sought to quantitatively examine mucosal inflammatory and immune responses in dogs with gastritis and the relationship of these responses to infection with Helicobacter. Gastric biopsies from 30 dogs were evaluated for B- and T-lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. Mucosal atrophy, fibrosis, cellularity, and severity of gastritis were graded qualitatively. Messenger-RNA (mRNA) for actin, interleukin-1beta (IL-1beta), IL-4, IL-8, and IL-10, transforming growth factor beta (TGF-beta), and interferon gamma (IFN-gamma) was quantified by polymerase chain reaction (PCR). The presence of Helicobacter spp. was determined by urease activity, histology, PCR, and enzyme-linked immunosorbent assay. mRNA for IL-1beta, IL-8, IL-10, TGF-beta, and IFN-gamma was detected in most dogs. IL-4 mRNA was detected in only 1 dog. Correlations were observed for IL-1beta versus IL-8 and IL-10; IL-8 versus IL-10, IFN-gamma, and TGF-beta; and IL-10 versus IFN-y. Mucosal pathology was related to cytokine mRNA expression (neutrophils to IL-8 and IFN-gamma, macrophages and lymphocytes to IFN-gamma, and fibrosis to IL-1beta). Gastritis was categorized as lymphoplasmacytic in all dogs, and its histologic severity correlated with atrophy, infiltration with lymphocytes and macrophages, and expression of IL-10 and IFN-gamma. Of the dogs examined, 76.7% were infected with Helicobacter spp. Infection was associated with increased expression of TGF-beta and fibrosis. Circulating anti-Helicobacter immunoglobulin G titers were higher in uninfected than infected dogs. We conclude that lymphoplasmacytic gastritis in dogs is characterized by concurrent activation of proinflammatory and immunomodulatory cytokines, with increased mRNA expression related to mucosal pathology. No significant associations between Helicobacter infection and proinflammatory cytokine expression, severity of gastritis, or differences in the pathogenicity of different Helicobacter spp. were found.     

Connective tissue growth factor expression in the rat remnant kidney model and association with tubular epithelial cells undergoing transdifferentiation

Connective tissue growth factor (CTGF) has been shown to mediate many actions of transforming growth factor-beta (TGF-beta) in the fibrotic response in several diseases. We compared expression of CTGF, TGF-beta, platelet-derived growth factor (PDGF), TNF-alpha, and interleukin-1 (IL-1) by in situ hybridization in Sprague-Dawley rats euthanized at 0, 2, 4, and 8 weeks after 5/6 nephrectomy using the rat remnant kidney model of renal failure. Collagen was evaluated by trichrome stains, immunohistochemistry, and electron microscopy. We compared expression patterns to cells undergoing metaplasia. Tubular epithelial regeneration and transdifferentiation to myofibroblasts were assessed morphologically and by proliferating cell nuclear antigen, smooth muscle actin, desmin, and vimentin immunohistochemistry. CTGF expression was minimal in controls, mild at 2 weeks and marked by 4 to 8 weeks in interstitial fibroblasts, coinciding with damage, regeneration, and fibrosis. TGF-beta expression was increased in many cell types at 2 weeks, increased further by 4 weeks, then remained constant. PDGF-B messenger RNA was found in many stromal cells at 2-4 weeks, but expression decreased at 8 weeks. No significant IL-1 or TNF-alpha staining was detected. We conclude that CTGF and interacting factors are associated with development or progression of chronic interstitial fibrosis. Proximity of CTGF, TGF-beta, and PDGF mRNA expression to regenerative epithelial cells and those transdifferentiating to myofibroblasts suggests that growth factors may modulate renal tubular epithelial differentiation.     

Positive correlation between renal tubular flattening and renal tubular injury/interstitial fibrosis in murine kidney disease models

The number of patients with chronic kidney disease (CKD) is growing continuously globally. In order to study pathogenesis and mechanisms, many animal models have been developed, including spontaneous, genetic, and induced models. Although each type of CKD shows disease-specific tissue changes in the early stages, tubular disorder and interstitial fibrosis histologically occur in the course of progression to end-stage renal failure. Therefore, the quantification of tubular disorder and interstitial fibrosis in CKD research using animal models is essential for measuring the degree of CKD severity and, thus, efficacy of therapeutic agents. Several strategies have been used to quantify interstitial fibrosis. Among scoring factors, renal tubular flattening can be quantitatively evaluated easily and inexpensively. However, the diagnostic value of renal tubular flattening evaluation has not been investigated previously. Therefore, in this study, we investigated the correlation between renal tubular flattening and interstitial fibrosis or renal tubular injury markers. We observed a strong correlation between the degree of tubular injury/interstitial fibrosis and renal tubular flattening in three types of mouse renal disease model. This is advantageous because rapidly advancing technologies such as artificial intelligence and image processing can be easily applied; hence, a more precise, objective, and quantitative diagnosis should be possible in the future.     

Calponin Expression in Renal Tubulointerstitial Fibrosis Induced in Rats by Cisplatin

Renal tubulointerstitial fibrosis is the common feature of chronic renal failure, regardless of its etiology. Myofibroblasts play important roles in progression of the fibrosis and are characterized by expressions of various cytoskeletons such as vimentin, desmin and α-smooth muscle actin (α-SMA). To pursue the characteristics of the cells, we immunohistochemically investigated the relationship between calponin (a marker of terminal smooth muscles) expression and myofibroblasts in cisplatin-induced rat renal tubulointerstitial fibrosis. Calponin-expressing interstitial cells increased with fibrosis and reacted simultaneously to vimentin or α-SMA (a marker of well-differentiated myofibroblasts) but not desmin or Thy-1 (a marker of myofibroblasts at the early stage). The present study shows that calponin may be expressed transiently in relatively well-developed myofibroblasts in rat renal fibrosis. Calponin could become a marker for myofibroblast development in chronic renal toxicity in rats.     

Characterization of the inflammatory infiltrate in canine chronic hepatitis.

Canine chronic hepatitis (CCH) is a progressive inflammatory disease of unknown etiology. To characterize the inflammatory infiltrate, 16 dogs with CCH were selected and classified into three groups based on the stage of fibrosis, as evaluated with Masson's trichrome stain. The inflammatory infiltrate in each liver section was immunohistochemically characterized and evaluated using CD3, lysozyme, lamba and kappa light chain, and alpha-smooth muscle actin antibodies. Numerous breeds were affected, and middle-aged females predominated in this select group. Necroinflammatory activity progressively increased and then waned as the hepatitis progressed to cirrhosis. CD3+ lymphocytes were the most numerous lymphoid cells in dogs with CCH. Degenerate hepatocytes were occasionally surrounded by CD3+ lymphocytes. Necrosis was positively correlated with the number of CD3+ lymphocytes. The lamba and kappa light chain-positive cell infiltrate was variable but generally mild. A positive correlation between the lambda and kappa light chain-positive cells and the portal alpha-smooth muscle actin was found. The number of alpha-smooth muscle actin-positive cells (myofibroblasts) in portal triads and fibrous septa was positively correlated with the stage of fibrosis. In contrast, no correlation was found between the number of lysozyme-positive cells (Kupffer cells) and the stage of fibrosis. These results further support the idea of an immune-mediated process in CCH and suggest that periductular myofibroblasts play an important role in canine liver fibrogenesis.     

Correlation of electrophoretic urine protein banding patterns with severity of renal damage in dogs with proteinuric chronic kidney disease

Background

Urine protein loss is common in dogs with chronic kidney disease (CKD). Currently available noninvasive means of evaluating CKD in dogs cannot accurately predict the severity of glomerular and tubulointerstitial damage. Electrophoretic analysis of urine proteins can indicate the compromised renal compartment (glomerular vs tubular), but extensive evaluation of protein banding pattern associations with histologic damage severity has not been performed in dogs.

Objectives

We aimed to evaluate electrophoretic banding patterns as indicators of the presence and severity of glomerular and tubulointerstitial damage in dogs with naturally occurring, predominantly proteinuric CKD.

Methods

We performed a retrospective study using urine and renal tissue from 207 dogs with CKD. Urine protein banding patterns were correlated with histologic severity of renal damage. Sensitivity and specificity of banding patterns for the detection of glomerular and tubulointerstitial damage were determined.

Results

Banding patterns were 97% sensitive and 100% specific for the detection of glomerular damage and 90% sensitive and 100% specific for the detection of tubulointerstitial damage. Correlations between composite banding patterns and the severity of renal damage were strong, while glomerular banding patterns correlated moderately with glomerular damage severity, and tubular gel scores correlated weakly to moderately with the severity of tubulointerstitial damage.

Conclusions and clinical importance

Urine protein banding patterns are useful for the detection of glomerular and tubulointerstitial damage in dogs with proteinuric CKD.     

Renal fibrosis in feline chronic kidney disease: Known mediators and mechanisms of injury

Chronic kidney disease (CKD) is a common medical condition of ageing cats. In most cases the underlying aetiology is unknown, but the most frequently reported pathological diagnosis is renal tubulointerstitial fibrosis. Renal fibrosis, characterised by extensive accumulation of extra-cellular matrix within the interstitium, is thought to be the final common pathway for all kidney diseases and is the pathological lesion best correlated with function in both humans and cats. As a convergent pathway, renal fibrosis provides an ideal target for the treatment of CKD and knowledge of the underlying fibrotic process is essential for the future development of novel therapies. There are many mediators and mechanisms of renal fibrosis reported in the literature, of which only a few have been investigated in the cat. This article reviews the process of renal fibrosis and discusses the most commonly cited mediators and mechanisms of progressive renal injury, with particular focus on the potential significance to feline CKD.     

Histologic and ultrastructural studies of juvenile onset renal disease in four Rottweiler dogs

Juvenile onset renal disease is described in 2 male and 2 female young Rottweiler dogs. Histologic changes in all dogs were cystic dilatation of Bowman's space, mesangial hypercellularity, and glomerulosclerosis. Three dogs also had glomerular crescents and moderate to severe interstitial fibrosis. Electron microscopy revealed glomerular basement membranes of variable thickness, with extensive splitting or lamellation of the lamina densa. These ultrastructural findings are similar to those found in people and in other breeds of dogs with inherited defects in type IV collagen.     

Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas

Fifteen fibrosarcomas, surgically excised from presumed sites of injection in dogs, and 10 canine fibrosarcomas excised from sites not used for injection were histologically and immunohistochemically compared with 20 feline post-vaccinal fibrosarcomas. Canine fibrosarcomas from presumed injection sites were of grade I (3), of grade II (4) and grade III (8). Two fibrosarcomas from non-injection sites were of grade I, four of grade II and four of grade III. Feline samples were classified as grade I (2), grade II (4) and grade III (14). All fibrosarcomas from presumed injection sites of both species showed lymphocytic inflammatory infiltration located at the tumour periphery, while two canine fibrosarcomas from non-injection sites showed perivascular inflammatory infiltration within the neoplasm. All samples were immunohistochemically examined for vimentin, smooth muscle actin, muscle specific actin and desmin expression. All tumours were positive for vimentin. Ten canine fibrosarcomas from presumed injection sites and all feline samples contained cells consistent with a myofibroblastic immunophenotype. Aluminium deposits were detected in eight canine fibrosarcomas from presumed injection sites and 11 feline post-vaccinal fibrosarcomas by the aurintricarboxylic acid method. The present study identifies distinct similarities between canine fibrosarcomas from presumed injection sites and feline post-vaccinal fibrosarcomas, suggesting the possibility of the development of post-injection sarcomas not only in cats, but also in dogs.     

Use of keyhole lung biopsy for diagnosis of interstitial lung diseases in dogs and cats: 13 cases (1998-2001)

OBJECTIVE: To characterize interstitial lung diseases (ILDs) and evaluate use of keyhole lung biopsy for diagnosis of ILDs in dogs and cats. DESIGN: Retrospective study. ANIMALS: 11 dogs and 2 cats. PROCEDURE: Medical records of dogs and cats undergoing keyhole lung biopsy to confirm ILDs were reviewed. Signalment, clinical signs, results of thoracic radiography and other respiratory diagnostic tests, postoperative complications, and patient outcome were analyzed. RESULTS: Clinical respiratory signs included cough, tachypnea, exercise intolerance, and hemoptysis. Thoracic radiographic abnormalities included interstitial, alveolar, and bronchointerstitial patterns and multiple discrete pulmonary nodules. Lung biopsy and histologic examination revealed interstitial pulmonary fibrosis, bronchiolitis obliterans with organizing pneumonia, or unclassified lesions. Outcome after biopsy included no response to treatment, euthanasia, partial or complete remission while receiving medication, and cure. CONCLUSIONS AND CLINICAL RELEVANCE: Recognition and classification of ILDs in dogs and cats are likely to be important in guiding appropriate treatment and providing accurate prognostic information. Ancillary respiratory diagnostic tests are beneficial in ruling out infectious and neoplastic disorders that may mimic ILDs; however, their present use in the diagnosis of ILDs is limited. Results suggest that keyhole lung biopsy is an effective means for obtaining a specimen for histologic diagnosis in dogs and cats with ILDs.     

Interactions between TGFβ1 and cyclic strain in modulation of myofibroblastic differentiation of canine mitral valve interstitial cells in 3D culture

ObjectivesThe mechanisms of myxomatous valve degeneration (MVD) are poorly understood. Transforming growth factor-beta1 (TGFβ1) induces myofibroblastic activation in mitral valve interstitial cells (MVIC) in static 2D culture, but the roles of more physiological 3D matrix and cyclic mechanical strain are unclear. In this paper, we test the hypothesis that cyclic strain and TGFβ1 interact to modify MVIC phenotype in 3D culture.Animals, materials and methodsMVIC were isolated from dogs with and without MVD and cultured for 7 days in type 1 collagen hydrogels with and without 5 ng/ml TGFβ1. MVIC with MVD were subjected to 15% cyclic equibiaxial strain with static cultures serving as controls. Myofibroblastic phenotype was assessed via 3D matrix compaction, cell morphology, and expression of myofibroblastic (TGFβ3, alpha-smooth muscle actin – αSMA) and fibroblastic (vimentin) markers.ResultsExogenous TGFβ1 increased matrix compaction by canine MVIC with and without MVD, which correlated with increased cell spreading and elongation. TGFβ1 increased αSMA and TGFβ3 gene expression, but not vimentin expression, in 15% cyclically stretched MVIC. Conversely, 15% cyclic strain significantly increased vimentin protein and gene expression, but not αSMA or TGFβ3. 15% cyclic strain however was unable to counteract the effects of TGFβ1 stimulation on MVIC.ConclusionsThese results suggest that TGFβ1 induces myofibroblastic differentiation (MVD phenotype) of canine MVIC in 3D culture, while 15% cyclic strain promotes a more fibroblastic phenotype. Mechanical and biochemical interactions likely regulate MVIC phenotype with dose dependence. 3D culture systems can systematically investigate these phenomena and identify their underlying molecular mechanisms.     

Iridociliary epithelial tumors in 100 dogs and 17 cats: a morphological study

The morphological features of iridociliary epithelial tumors in 100 dogs and 17 cats were reviewed. Twenty-seven cases were in either Golden Retrievers or Labrador Retrievers. Affected globes were stained for light microscopy with alcian blue, periodic acid Schiff (PAS) and hematoxylin and eosin stains. Selected tissues were examined by immunohistochemistry for vimentin, desmin, cytokeratin, S-100, neuron-specific enolase (NSE), and glial fibrillary acid protein (GFAP). The presence or absence of hyaluronic acid was recorded by staining with alcian blue before and after digestion of the tissue with hyaluronidase. Canine tumors were divided into papillary and solid tumors based on the pattern of growth. Twenty-eight of 57 papillary tumors exhibited invasive behavior including eight of the 57 which showed infiltration of the sclera. Twenty-nine of 43 solid tumors were invasive including 13 of 43 with scleral invasion. Tumors with scleral invasion were designated adenocarcinoma. Tumors of both types could be pigmented or nonpigmented and often contained smooth basement membranes reminiscent of the inner membrane of the nonpigmented ciliary body epithelial cell. All of the feline tumors were nonpigmented and 14 of 16 feline tumors were solid and two of the tumors were papillary. Eighteen of 20 canine tumors and three of four feline tumors stained positive for vimentin. Cytokeratin stain was positive only in a few of the highly aggressive tumors. The finding of pigmented epithelial cells, thick, smooth basement membrane structures, positive staining for vimentin, S-100, and NSE as well as hyaluronic acid deposition were considered to be features which define iridociliary epithelial tumors in dogs. The positive staining for vimentin and NSE are highly specific markers which help to characterize iridociliary epithelium and distinguish this tumor from metastatic epithelial tumors. The finding of solid nonpigmented tumors with small epithelial cells packeted by thin PAS-positive membranes staining positive for vimentin were considered significant features defining iridociliary epithelial tumors in cats. Follow-up information on survival and cause of death was obtained on 43 canine cases and only two feline cases. The average follow-up interval in dogs was 25 months and only two dogs died with lesions that could have been due to metastasis although neither was confirmed. We concluded that neither iridociliary adenomas nor adenocarcinomas is likely to metastasize.     

Use of continuous renal replacement therapy for treatment of dogs and cats with acute or acute-on-chronic renal failure: 33 cases (2002–2006)

Objective: To describe the indications, clinical features, outcomes and complications associated with use of continuous renal replacement therapy (CRRT) in 17 client-owned dogs and 16 client-owned cats with acute or acute-on-chronic renal failure refractory to aggressive medical management.
Series summary: Twenty-nine percent of dogs and 44% of cats had evidence of pre-existing chronic kidney disease (CKD). Median duration of CRRT was 16.3 hours (range 0.3–83.0 hours) in dogs and 11.5 hours (range 1.0–35.5 hours) in cats. Median canine blood urea nitrogen (BUN) improved from 41.0 mmol/L (115.0 mg/dL) to 11.8 mmol/L (33.0 mg/dL) and creatinine from 636.5 mmol/L (7.2 mg/dL) to 274 mmol/L (3.1 mg/dL). Median feline BUN improved from 46.4 mmol/L (130 mg/dL) to 13.9 mmol/L (39.0 mg/dL) and creatinine from 1069.6 mmol/L (12.1 mg/dL) to 291.7 mmol/L (3.3 mg/dL). Metabolic acidosis resolved in 80% of affected dogs and 71% of affected cats. Hyperkalemia resolved in 100% of affected dogs and 88% of affected cats. Complications noted with CRRT included iatrogenic hypokalemia, iatrogenic metabolic alkalosis, clinical hypocalcemia, total hypercalcemia, filter clotting, anemia, hypothermia, and neurologic complications. Forty-one percent of dogs and 44% of cats survived to discharge. No dogs and only 1 cat developed newly diagnosed CKD.
New or unique information provided: CRRT can be a viable option for the management of acute or acute-on-chronic renal failure in dogs and cats that are refractory to aggressive medical management. The frequency of complications associated with CRRT in this study warrants further experience with this modality before its widespread use can be recommended.     

Immunohistochemical evaluation of intermediate filament expression in canine and feline neoplasms

Specimens of neoplastic tissues from 19 dogs and 4 cats were examined immunohistochemically for intermediate filament expression, using commercially available antibodies. Staining was observed in a wide range of tumor tissues and in normal internal controls by use of antibodies to vimentin, desmin, glial fibrillary acidic protein, and low and high molecular weight cytokeratins. Intermediate filament expression was found to be consistent with light and/or electron microscopic findings, and hence believed to be an accurate indicator of tumor histogenesis in cats and dogs. Three fixatives were evaluated for their relative abilities to preserve antigenicity. Absolute alcohol was superior to B5 fixative and both were superior to formalin. Some tissues that clearly displayed intermediate filament antigens with alcohol and B5 fixative failed to stain when fixed in formalin.     

Relationship among Serum Creatinine,Serum Gastrin,Calcium‐phosphorus Product,and Uremic Gastropathy in Cats with Chronic Kidney Disease

Background

Chronic kidney disease (CKD) in cats is associated with gastrointestinal signs commonly attributed to uremic gastropathy. Consequently, patients often are treated with antacids and gastrointestinal protectants. This therapeutic regimen is based on documented gastric lesions in uremic humans and dogs, but the nature and incidence of uremic gastropathy in cats are unknown.

Hypothesis/Objectives

Evaluate uremic gastropathy in CKD cats to facilitate refinement of medical management for gastrointestinal signs.

Animals

Thirty‐seven CKD cats; 12 nonazotemic cats

Methods

Stomachs were evaluated for the presence of classic uremic gastropathy lesions. Histopathologic lesions were compared with serum creatinine concentrations, calcium‐phosphorus product (CPP), and serum gastrin concentrations.

Results

Gastric ulceration, edema, and vascular fibrinoid change were not observed. The most important gastric lesions in CKD cats were fibrosis and mineralization. Sixteen CKD cats (43%) had evidence of gastric fibrosis of varying severity and 14 CKD cats (38%) had gastric mineralization. CKD cats were more likely to have gastric fibrosis and mineralization than nonazotemic controls (P = .005 and P = .021, respectively). Only cats with moderate and severe azotemia had gastric mineralization. CPP was correlated with disease severity; severely azotemic CKD cats had significantly higher CPP when compared with nonazotemic controls, and to mildly and moderately azotemic cats (P < .05). Gastrin concentrations were significantly higher in CKD cats when compared with nonazotemic controls (P = .003), but increased concentrations were not associated with gastric ulceration.

Conclusions and Clinical Importance

Uremic gastropathy in CKD cats differs from that described in other species and this difference should be considered when devising medical management.     

Expression of alpha-smooth muscle actin and fibronectin in tubulointerstitial lesions of cats with chronic renal failure

OBJECTIVE: To examine renal expression of alpha-smooth muscle actin (alpha-SMA) and fibronectin in cats with tubulointerstitial nephritis (TIN) for use in predicting progression to renal fibrosis. ANIMALS: 19 cats with TIN and 9 cats without nephritis. PROCEDURE: Serum creatinine and BUN concentrations were measured. Indices for glomerular extra-cellular matrix (ECM), tubular injury (TI), and fibronectin were determined in renal specimens to quantify the extent of injury and fibrotic lesions. Expression of alpha-SMA in renal tissue was immunohistochemically detected, and correlations were evaluated between the alpha-SMA index and other histologic and clinical variables. RESULTS: The alpha-SMA index in tubulointerstitial areas (1.63 +/- 0.78) was significantly higher in cats with TIN, especially in the periglomerular and peritubular areas, than in cats without nephritis (0.20 +/- 0.14). The alpha-SMA index was significantly associated with the TI index (r2 = 0.70), fibronectin index (r2 = 0.95), BUN concentration (r = 0.64), and serum creatinine concentration () = 0.66). Of special interest was that interstitial alpha-SMA expression appeared evident in the kidneys at an early stage of TIN, prior to the onset of ECM deposition. CONCLUSION AND CLINICAL RELEVANCE: Analysis of results of histologic and clinical examinations revealed that interstitial alpha-SMA expression may have clinical importance and may be a useful early histologic marker for development of chronic renal failure in cats. An immunohistochemical examination for fibrogenic molecules (such as alpha-SMA expression) may provide fundamental information on the pathogenesis of early-stage renal disease and aid clinical management of cats with chronic renal failure, including TIN.     

Measurement, interpretation, and implications of proteinuria and albuminuria.

Proteinuria is a common disorder in dogs and cats that can indicate the presence of chronic kidney disease (CKD) before the onset of azotemia or the presence of more severe CKD after the onset of azotemia. Although a direct pathogenetic link between glomerular disease, proteinuria, and progressive renal damage has not been established, attenuation of proteinuria has been associated with decreased renal functional decline in several studies. There is a need to continue to increase our understanding of the effects of proteinuria on the glomerulus, the tubule, and the interstitium in dogs and cats.     

Survival and the Development of Azotemia after Treatment of Hyperthyroid Cats

Background: Hyperthyroidism complicates the diagnosis of chronic kidney disease (CKD) as it increases glomerular filtration rate. No practical and reliable means for identifying those cats that will develop azotemia after treatment for hyperthyroidism has been identified. Hyperthyroidism is associated with proteinuria. Proteinuria has been correlated with decreased survival of cats with CKD and with progression of CKD. Hypothesis: Proteinuria and other clinical parameters measured at diagnosis of hyperthyroidism will be associated with the development of azotemia and survival time. Animals: Three hundred client owned hyperthyroid cats treated in first opinion practice. Methods: Retrospective, cohort study relating clinical parameters in hyperthyroid cats at diagnosis to the development of azotemia within 240 days of diagnosis and survival time (all cause mortality). Multivariable logistic regression analysis was used to identify factors that were predictive of the development of azotemia. Multivariable Cox regression analysis was used to identify factors associated with survival. Results: Three hundred cats were eligible for survival analysis and 216 cats for analysis of factors associated with the development of azotemia. The median survival time was 417 days, and 15.3% (41/268) cats developed azotemia within 240 days of diagnosis of hyperthyroidism. Plasma concentrations of urea and creatinine were positively correlated with the development of azotemia. Plasma globulin concentration was negatively correlated with the development of azotemia. Age, urine protein : creatinine ratio, and the presence of hypertension were significantly correlated with decreased survival time. Urine specific gravity and PCV were significantly correlated with increased survival time. Conclusions and Clinical Importance: The proteinuria associated with hyperthyroidism is not a mediator of progression of CKD; however, it does correlate with all cause mortality.