Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs.

BACKGROUND: Symmetric dimethylarginine (SDMA) is a small molecule formed by methylation of arginine, and released into blood during protein degradation. SDMA is primarily eliminated by renal excretion and is a promising endogenous marker of glomerular filtration rate (GFR). OBJECTIVES: To validate an assay for SDMA measurement, determine stability of SDMA in blood, and compare SDMA with serum creatinine concentration (sCr) and GFR for early detection of decreasing kidney function in dogs with chronic kidney disease (CKD). ANIMALS: Eight male dogs affected with X-linked hereditary nephropathy and 4 unaffected male littermates. METHODS: Prospective study validating SDMA measurement using liquid chromatography-mass spectrometry, assessing stability of SDMA in serum and plasma, and serially determining sCr, SDMA, and GFR (using iohexol clearance) in dogs during progression from preclinical disease to end-stage renal failure. Correlations were determined using linear regression. Timepoints at which sCr, SDMA, and GFR identified decreased renal function were compared using defined cutoffs, trending in an individual dog, and comparison with unaffected littermates. RESULTS: Symmetric dimethylarginine was highly stable in serum and plasma, and the assay demonstrated excellent analytical performance. In unaffected dogs, SDMA remained unchanged whereas in affected dogs, SDMA increased during disease progression, correlating strongly with an increase in sCr (r = 0.95) and decrease in GFR (r = -0.95). Although trending improved sCr's sensitivity, SDMA identified, on average, <20% decrease in GFR, which was earlier than sCr using any comparison method. CONCLUSIONS AND CLINICAL IMPORTANCE: Symmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs with CKD.

Age-related injury and compensation claim rates in heavy industry.

BACKGROUND: Although ageing workers face specific health and safety concerns, conflicting evidence exists regarding the effects of age on workplace injury rates and workers' compensation claims. AIMS: To examine injury and workers' compensation claim rates by age and injury type in an aluminium smelter over a 9-year period. METHODS: Routinely collected data for workplace injuries and workers' compensation claims were retrieved for the period from 1997 to 2005. RESULTS: The study included a total of 709 workers who experienced 2281 at-work injuries and submitted 446 claims. In 1997, 16% of employees were aged 50 or over; by 2005 that proportion had more than doubled to 35%. Injury and claim rates in all age groups did not change significantly during this period. Workers younger than 30 years of age had the highest injury rates, with differences most significant for injuries other than sprains and strains. Claim rates were not significantly different across age groups. CONCLUSIONS: These findings do not provide evidence to support the notion that older workers sustain more injuries and are more likely to claim compensation for their injuries. Our findings demonstrate that in this workplace, older workers were able to maintain their ability to work safely. This contrasts with the finding that younger workers had the highest injury and claim rates. While adapting to the needs of an ageing workforce, employers should not lose sight of the need to nurture a strong culture of working safely among their youngest workers.

Long-term outcome in dogs with patent ductus arteriosus: 520 cases (1994-2009).

BACKGROUND: Published information regarding survival and long-term cardiac remodeling after patent ductus arteriosus (PDA) closure in dogs is limited. OBJECTIVES: To report outcome and identify prognostic variables in dogs with PDA, and to identify risk factors for persistent remodeling in dogs with a minimum of 12 months of follow-up after closure. ANIMALS: Five hundred and twenty client-owned dogs. METHODS: Retrospective review of medical records of 520 dogs with PDA. Outcome was determined by contacting owners and veterinarians. Dogs with PDA closure and ≥ 12 months of follow-up were asked to return for a re-evaluation. RESULTS: In multivariable analysis of 506 dogs not euthanized at the time of diagnosis, not having a PDA closure procedure negatively affected survival (HzR = 16.9, P < .001). In 444 dogs undergoing successful PDA closure, clinical signs at presentation (HzR = 17, P = .02), concurrent congenital heart disease (HD) (HzR = 4.8, P = .038), and severe mitral regurgitation (MR) documented within 24 hours of closure (HzR = 4.5, P = .028) negatively affected survival. Seventy-one dogs with ≥ 12 months follow-up demonstrated a significant reduction in radiographic and echocardiographic measures of heart size (P = 0) and increased incidence of acquired HD (P = .001) at re-evaluation. Dogs with increased left ventricular size and low fractional shortening at baseline were more likely to have persistent remodeling at re-evaluation. CONCLUSIONS AND CLINICAL IMPORTANCE: Patent ductus arteriosus closure confers important survival benefits and results in long-term reverse remodeling in most dogs. Clinical signs at presentation, concurrent congenital HD, and severe MR negatively affect survival. Increased left ventricular systolic dimensions and systolic dysfunction at baseline correlated significantly with persistent remodeling.

Urinary biomarkers of renal disease in dogs with X-linked hereditary nephropathy.

BACKGROUND: Sensitive and specific biomarkers for early tubulointerstitial injury are lacking. HYPOTHESIS: The excretion of certain urinary proteins will correlate with the state of renal injury in dogs with chronic kidney disease. ANIMALS: Twenty-five male colony dogs affected with X-linked hereditary nephropathy (XLHN) and 19 unaffected male littermates were evaluated. METHODS: Retrospective analysis of urine samples collected every 2-4 weeks was performed. Urine proteins evaluated were retinol binding protein (uRBP/c), ß2-microglobulin (uB2M), N-acetyl-ß-D-glucosaminidase (uNAG/c), neutrophil gelatinase-associated lipocalin (uNGAL/c), and immunoglobulin G (uIgG/c). Results were correlated with serum creatinine concentration (sCr), glomerular filtration rate (GFR), urine protein : creatinine ratio, and histopathologic analysis of serial renal biopsies. Analytical validation was performed for all assays; uNAG stability was evaluated. RESULTS: All urinary biomarkers distinguished affected dogs from unaffected dogs early in their disease process, increasing during early and midstages of disease. uRBP/c correlated most strongly with conventional measures of disease severity, including increasing sCr (r = 0.89), decreasing GFR (r = -0.77), and interstitial fibrosis (r = 0.80), P < .001. However, multivariate analysis revealed age, sCr, uIgG/c, and uB2M, but not uRBP/c, as significant independent predictors of GFR (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: All urinary biomarkers were elevated before sCr increased, but typically after proteinuria developed in dogs with progressive glomerular disease because of XLHN. uRBP/c measurement might be promising as a noninvasive tool for diagnosis and monitoring of tubular injury and dysfunction in dogs.

Technical note: Analysis of ordinal outcomes from carcass data in beef cattle research.

Beef cattle research commonly uses Yield grade (YG) and Quality grade (QG) as outcomes in nutrition and health experiments. These outcomes, as commonly reported and analyzed, are ordinal variables with an assumed rank derived from an underlying latent variable that may or may not be available for analysis. The objective of this study was to employ mixed-effects ordinal regression and approaches previously reported in animal science and veterinary literature such as contingency table analysis, mixed-effects linear regression, and mixed-effects logistic regression for the analysis of YG and QG data and to compare results with respect to statistical significance and estimated statistical power. Five randomized complete block design experiments were used for initial evaluation. Simulated data sets were used for evaluation of relative differences in statistical power. Scenarios were observed where all of the methods differed in estimate of effect and statistical significance. Power to detect an association was similar between studies under the scenario evaluated. Ordinal regression approaches provide an estimate of effect that can be used in subsequent prediction of performance, which is an advantage over contingency table approaches that only report statistical significance. Further, ordinal models do not require modification of the outcome variable as in logistic regression or assumptions regarding YG or QG distribution in linear regression, which are often not met. Researchers faced with analysis of YG and QG data should consider the use of ordinal regression, particularly with recent advances in statistical software packages capable of implementing this method for data within hierarchical models.