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

Serum Concentrations of Symmetric Dimethylarginine and Creatinine in Dogs with Naturally Occurring Chronic Kidney Disease

Citation: Hall, J. A., Yerramilli, M., Obare, E., Yerramilli, M., Almes, K., & Jewell, D. E. (2016). Serum Concentrations of Symmetric Dimethylarginine and Creatinine in Dogs with Naturally Occurring Chronic Kidney Disease. Journal of Veterinary Internal Medicine, 30(3), 794-802. doi:10.1111/jvim.13942Background: Serum concentrations of symmetric dimethylarginine (SDMA) detected chronic kidney disease (CKD) in cats an average of 17.0 months before serum creatinine (Cr) concentrations increased above the reference interval. Objectives: To report on the utility of measuring serum SDMA concentrations in dogs for detection of CKD before diagnosis by measurement of serum Cr. Animals: CKD dogs (n = 19) included those persistently azotemic for ?3 months (n = 5), dogs that were azotemic at the time of death (n = 4), and nonazotemic dogs (n = 10). CKD dogs were compared with healthy control dogs (n = 20). Methods: Retrospective study, whereby serum Cr concentrations were determined by enzymatic colorimetry and serum SDMA concentrations were determined by liquid chromatography-mass spectrometry in dogs with necropsy confirmed CKD. Results: Serum SDMA increased before serum Cr in 17 of 19 dogs (mean, 9.8 months; range, 2.2-27.0 months). Duration of elevations in serum SDMA concentrations before the dog developed azotemia (N = 1) or before the dog died (N = 1) was not determined. Serum SDMA and Cr concentrations were linearly related (r = 0.84; P < .001). Serum SDMA (r = -0.80) and serum Cr (r = -0.89) concentrations were significantly related to glomerular filtration rate (both P < .001). Conclusion and Clinical Importance: Using serum SDMA as a biomarker for CKD allows earlier detection of kidney dysfunction in dogs than does measurement of serum Cr. Earlier detection might be desirable for initiating renoprotective interventions that slow progression of kidney disease. © 2016 American College of Veterinary Internal Medicine

Comparison of the diagnostic value of symmetric dimethylarginine, cystatin C, and creatinine for detection of decreased glomerular filtration rate in dogs

BACKGROUND: Early detection of decreased glomerular filtration rate (GFR) in dogs is challenging. Current methods are insensitive and new biomarkers are required. OBJECTIVE: To compare overall diagnostic performance of serum symmetric dimethylarginine (SDMA) and serum cystatin C to serum creatinine, for detection of decreased GFR in clinically stable dogs, with or without chronic kidney disease (CKD). ANIMALS: Ninety-seven client-owned dogs: 67 dogs with a diagnosis or suspicion of CKD and 30 healthy dogs were prospectively included. METHODS: Prospective diagnostic accuracy study. All dogs underwent physical examination, systemic arterial blood pressure measurement, urinalysis, hematology and blood biochemistry analysis, cardiac and urinary ultrasound examinations, and scintigraphy for estimation of glomerular filtration rate (mGFR). Frozen serum was used for batch analysis of SDMA and cystatin C. RESULTS: The area under the curve of creatinine, SDMA, and cystatin C for detection of an mGFR &lt;30.8 mL/min/L was 0.98 (95% confidence interval [CI], 0.93-1.0), 0.96 (95% CI, 0.91-0.99), and 0.87 (95% CI, 0.79-0.93), respectively. The sensitivity of both creatinine and SDMA at their prespecified cutoffs (115 μmol/L [1.3 mg/dL] and 14 μg/dL) for detection of an abnormal mGFR was 90%. The specificity was 90% for creatinine and 87% for SDMA. When adjusting the cutoff for cystatin C to correspond to a diagnostic sensitivity of 90% (0.49 mg/L), specificity was lower (72%) than that of creatinine and SDMA. CONCLUSIONS AND CLINICAL IMPORTANCE: Overall diagnostic performance of creatinine and SDMA for detection of decreased mGFR was similar. Overall diagnostic performance of cystatin C was inferior to both creatinine and SDMA

Analyzing the Impacts of Dams on Riparian Ecosystems: A Review of Research Strategies and Their Relevance to the Snake River Through Hells Canyon

River damming provides a dominant human impact on river environments worldwide, and while local impacts of reservoir flooding are immediate, subsequent ecological impacts downstream can be extensive. In this article, we assess seven research strategies for analyzing the impacts of dams and river flow regulation on riparian ecosystems. These include spatial comparisons of (1) upstream versus downstream reaches, (2) progressive downstream patterns, or (3) the dammed river versus an adjacent free-flowing or differently regulated river(s). Temporal comparisons consider (4) pre- versus post-dam, or (5) sequential post-dam conditions. However, spatial comparisons are complicated by the fact that dams are not randomly located, and temporal comparisons are commonly limited by sparse historic information. As a result, comparative approaches are often correlative and vulnerable to confounding factors. To complement these analyses, (6) flow or sediment modifications can be implemented to test causal associations. Finally, (7) process-based modeling represents a predictive approach incorporating hydrogeomorphic processes and their biological consequences. In a case study of Hells Canyon, the upstream versus downstream comparison is confounded by a dramatic geomorphic transition. Comparison of the multiple reaches below the dams should be useful, and the comparison of Snake River with the adjacent free-flowing Salmon River may provide the strongest spatial comparison. A pre- versus post-dam comparison would provide the most direct study approach, but pre-dam information is limited to historic reports and archival photographs. We conclude that multiple study approaches are essential to provide confident interpretations of ecological impacts downstream from dams, and propose a comprehensive study for Hells Canyon that integrates multiple research strategies

Evaluation of the public health impacts of traffic congestion: a health risk assessment

Background: Traffic congestion is a significant issue in urban areas in the United States and around the world. Previous analyses have estimated the economic costs of congestion, related to fuel and time wasted, but few have quantified the public health impacts or determined how these impacts compare in magnitude to the economic costs. Moreover, the relative magnitudes of economic and public health impacts of congestion would be expected to vary significantly across urban areas, as a function of road infrastructure, population density, and atmospheric conditions influencing pollutant formation, but this variability has not been explored. Methods: In this study, we evaluate the public health impacts of ambient exposures to fine particulate matter (PM2.5) concentrations associated with a business-as-usual scenario of predicted traffic congestion. We evaluate 83 individual urban areas using traffic demand models to estimate the degree of congestion in each area from 2000 to 2030. We link traffic volume and speed data with the MOBILE6 model to characterize emissions of PM2.5 and particle precursors attributable to congestion, and we use a source-receptor matrix to evaluate the impact of these emissions on ambient PM2.5 concentrations. Marginal concentration changes are related to a concentration-response function for mortality, with a value of statistical life approach used to monetize the impacts. Results: We estimate that the monetized value of PM2.5-related mortality attributable to congestion in these 83 cities in 2000 was approximately $31 billion (2007 dollars), as compared with a value of time and fuel wasted of$60 billion. In future years, the economic impacts grow (to over $100 billion in 2030) while the public health impacts decrease to$13 billion in 2020 before increasing to $17 billion in 2030, given increasing population and congestion but lower emissions per vehicle. Across cities and years, the public health impacts range from more than an order of magnitude less to in excess of the economic impacts. Conclusions: Our analyses indicate that the public health impacts of congestion may be significant enough in magnitude, at least in some urban areas, to be considered in future evaluations of the benefits of policies to mitigate congestion