Evaluation of cystatin C for the detection of chronic kidney disease in cats

BackgroundSerum cystatin C (sCysC) and urinary cystatin C (uCysC) are potential biomarkers for early detection of chronic kidney disease (CKD) in cats. An in-depth clinical validation is required. ObjectivesTo evaluate CysC as a marker for CKD in cats and to compare assay performance of the turbidimetric assay (PETIA) with the previously validated nephelometric assay (PENIA). AnimalsNinety cats were included: 49 CKD and 41 healthy cats. MethodsSerum CysC and uCysC concentrations were prospectively evaluated in cats with CKD and healthy cats. Based on plasma exo-iohexol clearance test (PexICT), sCysC was evaluated to distinguish normal, borderline, and low GFR. Sensitivity and specificity to detect PexICT<1.7mL/min/kg were calculated. Serum CysC results of PENIA and PETIA were correlated with GFR. Statistical analysis was performed using general linear modeling. ResultsCats with CKD had significantly higher meanSD sCysC (1.4 +/- 0.5mg/L) (P<.001) and uCysC/urinary creatinine (uCr) (291 +/- 411mg/mol) (P<.001) compared to healthy cats (sCysC 1.0 +/- 0.3 and uCysC/uCr 0.32 +/- 0.97). UCysC was detected in 35/49 CKD cats. R-2 values between GFR and sCysC or sCr were 0.39 and 0.71, respectively (sCysC or sCr=+GFR+epsilon). Sensitivity and specificity were 22 and 100% for sCysC and 83 and 93% for sCr. Serum CysC could not distinguish healthy from CKD cats, nor normal from borderline or low GFR, in contrast with sCr. ConclusionSerum CysC is not a reliable marker of reduced GFR in cats and uCysC could not be detected in all CKD cats

Fibronectin binding of persistent versus resolving methicillin-resistant Staphylococcus aureus bacteremia isolates

Staphylococcus aureus bacterial infection is a serious problem in medicine. The initial and necessary step in virtually all S. aureus infections is binding of a bacterium to surfaces within a host (e.g., tissue or indwelling device). One of the most important binding reactions is between human fibronectin (e.g., presented on endothelial cells or coatings on prosthetic heart values) and fibronectin-binding proteins produced on the surface of S. aureus. I propose that S. aureus isolates that exhibit a clinically complicated progression of infection will show stronger and more frequent binding to fibronectin-coated surfaces in vitro. This study used methicillin- resistant S. aureus (MRSA) isolates from two distinct clinical populations: patients whose bacterial infection resolved within 4 days of antibiotic treatment (n = 7; resolving bacteremia; RB), and patients who still had positive MRSA blood cultures after ≥7 days of receiving antibiotics (n = 7; persistent bacteremia; PB). Fibronectin binding was experimentally measured by using atomic force microscopy (AFM) to probe attractive forces between a fibronectin-coated AFM tip and putative fibronectin-binding receptors on S. aureus cells from each of the 14 isolates. The bacterial isolates that originated from patients that had PB showed statistically higher binding frequency (p = 0.0218), force of binding (p <0.0001), and energy of binding (p <0.0001) relative to RB isolates. These measurements suggest that binding to fibronectin is associated with increased risk of serious infection by S. aureus.No embarg

Re-Examining American Cold War Foreign Policy Between 1976 and 1980 Using Select Newspaper Editorials

This thesis examines how select newspaper editorial sections covered certain American Cold War foreign policy decisions between 1976 and 1980.No embarg

Risk Factors for Development of Chronic Kidney Disease in Cats

BACKGROUND: Identification of risk factors for development of chronic kidney disease (CKD) in cats may aid in its earlier detection. HYPOTHESIS/OBJECTIVES: Evaluation of clinical and questionnaire data will identify risk factors for development of azotemic CKD in cats. ANIMALS: One hundred and forty‐eight client‐owned geriatric (>9 years) cats. METHODS: Cats were recruited into the study and followed longitudinally for a variable time. Owners were asked to complete a questionnaire regarding their pet at enrollment. Additional data regarding dental disease were obtained when available by development of a dental categorization system. Variables were explored in univariable and multivariable Cox regression models. RESULTS: In the final multivariable Cox regression model, annual/frequent vaccination (P value, .003; hazard ratio, 5.68; 95% confidence interval, 1.83–17.64), moderate dental disease (P value, .008; hazard ratio, 13.83; 95% confidence interval, 2.01–94.99), and severe dental disease (P value, .001; hazard ratio, 35.35; 95% confidence interval, 4.31–289.73) predicted development of azotemic CKD. CONCLUSION: Our study suggests independent associations between both vaccination frequency and severity of dental disease and development of CKD. Further studies to explore the pathophysiological mechanism of renal injury for these risk factors are warranted

Determination of extracellular fluid volume in healthy and azotemic cats

BACKGROUND: Methods for determining extracellular fluid volume (ECFV) are important clinically for cats. Bromide dilution has been studied in cats to estimate ECFV. Markers of GFR also distribute in ECFV and can be used for its measurement. HYPOTHESIS/OBJECTIVES: The primary objective was to develop a method of determining ECFV from iohexol clearance in cats and evaluate agreement with that determined using bromide dilution. Additional objectives were to compare ECFV between azotemic and nonazotemic cats and evaluate appropriate methods of standardizing ECFV. ANIMALS: Client‐owned cats with varying renal function. METHODS: Validation of ECFV determined from slope‐intercept iohexol clearance was performed in 18 healthy nonazotemic cats. ECFV was then determined using the validated method and bromide dilution and agreement assessed. Appropriateness of standardization to body weight (BW) and body surface area (BSA) was evaluated. RESULTS: Extracellular fluid volume determined from slope‐intercept iohexol clearance and bromide dilution was 0.84 ± 0.32 L and 0.85 ± 0.19 L (mean ± SD), respectively. There were wide limits of agreement between the methods (−0.58 to 0.54 L) and therefore, agreement was considered to be poor. ECFV did not differ significantly between azotemic and nonazotemic cats (P = .177). BSA was found to be the best method for standardizing ECFV measurement in cats. CONCLUSIONS AND CLINICAL IMPORTANCE: This study developed a method for determining ECFV from slope‐intercept iohexol clearance which provides simultaneous assessment of renal function and an estimate of ECFV. ECFV does not differ between azotemic and nonazotemic cats, which suggests fluid volume loss or overload is not an important clinical feature in cats with mild chronic kidney disease

Urinary active transforming growth factor ß in feline chronic kidney disease

The cytokine transforming growth factor beta 1 (TGF-β1) has been widely implicated in the development and progression of renal fibrosis in chronic kidney disease (CKD) in humans and in experimental models. The aims of this study were to assess the association between urinary active TGF-β1 and (a) development of CKD in a cross-sectional study, (b) deterioration of renal function over 1 year in a longitudinal study, and (c) renal histopathological parameters in cats. A human active TGF-β1 ELISA was validated for use in feline urine. Cross-sectional analysis revealed no significant difference in urinary active TGF-β1:creatinine ratio (aTGF-β1:UCr) between groups with differing renal function. Longitudinally, non-azotaemic cats that developed CKD demonstrated a significant (P = 0.028) increase in aTGF-β1:UCr approximately 6 months before the development of azotaemia, which remained elevated (P = 0.046) at diagnosis (approximately 12 months prior, 8.4 pg/mg; approximately 6 months prior, 22.2 pg/mg; at CKD diagnosis, 24.6 pg/mg). In the histopathology study, aTGF-β1:UCr was significantly higher in cats with moderate (P = 0.02) and diffuse (P = 0.005) renal fibrosis than in cats without fibrosis. Cats with moderate renal inflammation had significantly higher urinary active aTGF-β1 concentrations than cats with mild (P = 0.035) or no inflammatory change (P = 0.004). The parameter aTGF-β1:UCr was independently associated with Log urine protein:creatinine ratio in a multivariable analysis of clinicopathological parameters and interstitial fibrosis score in a multivariable analysis of histopathological features. These results suggest that urinary aTGF-β1 reflects the severity of renal pathology. Increases in urinary aTGF-β1 followed longitudinally in individual cats may indicate the development of CKD