NGAL: a new missing link between inflammation and uremic anemia?

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Renal Concerns in the Treatment of Chronic Hepatitis B with Tenofovir

Tenofovir, a third generation oral nucleos(t)ide analogue, currently represents one of the first-line drugs recommended for treating chronic hepatitis B virus (HBV) infection. After oral administration, tenofovir is mostly excreted in the urine by glomerular filtration and proximal tubular secretion. Hence, an impaired kidney function may lead to an increased renal exposure to the drug in patients with coexistent renal damage. This could further worsen kidney disease through different mechanisms of nephrotoxicity such as mitochondrial DNA depletion and tubular cytotoxicity. Despite several studies performed so far to assess tenofovir-related renal toxicity, data in HBV patients are not yet conclusive. Screening of risk factors for kidney disease before starting therapy and a careful monitoring of serum creatinine, glomerular filtration rate, serum phosphate and urine analysis during treatment are advocated to adjust the dose or stop treatment if needed. New biomarkers of tubular injury, such as neutrophil gelatinase associated lipocalin, could become helpful in the future for the timely identification and risk stratification of renal damage induced by tenofovir

Differential cost analysis with simultaneous potentials and anti-potentials

We present a novel approach to differential cost analysis that, given a program revision, attempts to statically bound the difference in resource usage, or cost, between the two program versions. Differential cost analysis is particularly interesting because of the many compelling applications for it, such as detecting resource-use regressions at code-review time or proving the absence of certain side-channel vulnerabilities. One prior approach to differential cost analysis is to apply relational reasoning that conceptually constructs a product program on which one can over-approximate the difference in costs between the two program versions. However, a significant challenge in any relational approach is effectively aligning the program versions to get precise results. In this paper, our key insight is that we can avoid the need for and the limitations of program alignment if, instead, we bound the difference of two cost-bound summaries rather than directly bounding the concrete cost difference. In particular, our method computes a threshold value for the maximal difference in cost between two program versions simultaneously using two kinds of cost-bound summaries---a potential function that evaluates to an upper bound for the cost incurred in the first program and an anti-potential function that evaluates to a lower bound for the cost incurred in the second. Our method has a number of desirable properties: it can be fully automated, it allows optimizing the threshold value on relative cost, it is suitable for programs that are not syntactically similar, and it supports non-determinism. We have evaluated an implementation of our approach on a number of program pairs collected from the literature, and we find that our method computes tight threshold values on relative cost in most examples

Obestatin: a new element for mineral metabolism and inflammation in patients on hemodialysis.

Background: Obestatin plays a key role in the process of energy balance maintenance with an anorectic effect. The main aim of the study was to evaluate obestatin in uremic patients to determine whether it is correlated with nutritional and inflammatory status. Methods: We studied plasma obestatin in uremic patients (n = 50) undergoing hemodialysis therapy and in healthy subjects. Plasma obestatin was measured using an ELISA kit. Results: Obestatin levels in uremic patients were lower than in healthy subjects (p 23 had lower obestatin levels than those with a BMI Conclusions: Based on the present observational data, obestatin might be implicated in the inflammatory state and the disturbances of calcium/phosphate metabolism of hemodialysis patients. However, further studies are warranted to determine whether this hormone plays a key role in contributing to malnutrition and to the chronic inflammatory process

Short-term vascular hemodynamic responses to isometric exercise in young adults and in the elderly

Background: Vascular aging is known to induce progressive stiffening of the large elastic arteries, altering vascular hemodynamics under both rest and stress conditions. In this study, we aimed to investigate changes in vascular hemodynamics in response to isometric handgrip exercise across ages. Participants and methods: We included 62 participants, who were divided into three age categories: 20-40 (n=22), 41-60 (n=20), and 61-80 (n=20) years. Vascular hemodynamics were measured using the Mobil-o-Graph® based on the pulsatile pressure changes in the brachial artery. One-way ANOVA test was performed to analyze the changes induced by isometric handgrip exercise. Results: After isometric handgrip exercise, aortic pulse wave velocity (PWV) increased by 0.10 m/s in the youngest, 0.06 m/s in the middle-age, and 0.02 m/s in the oldest age category. Changes in PWV strongly correlated with those in central systolic blood pressure (cSBP) (r=0.878, P<0.01). After isometric exercise, the mean change of systolic blood pressure (SBP) was −1.9% in the youngest, 0.6% in the middle-aged, and 8.2% in the oldest subjects. Increasing handgrip strength was associated with an increase in SBP and cSBP (1.08 and 1.37 mmHg per 1 kg increase in handgrip strength, res

Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study

Aims: To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial. Methods and results: Circulating cardiac [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT)], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal (cystatin C), and inflammatory [high-sensitivity C-reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 participants with complete data. The relationship between these biomarkers and the primary composite endpoint of heart failure hospitalization or cardiovascular death over 28 months of follow-up (n = 834) was evaluated using Cox proportional hazards regression, the c-statistic and the net reclassification index (NRI). After adjustment, the hazard ratio (HR) for the composite outcome in the top tertile of the distribution compared to the lowest tertile for each biomarker was: NT-proBNP 3.96 (95% CI 3.16–4.98), hsTnT 3.09 (95% CI 2.47–3.88), MR-proADM 2.28 (95% CI 1.83–2.84), copeptin 1.66 (95% CI 1.35–2.04), cystatin C 1.92 (95% CI 1.55–2.37), and hsCRP 1.51 (95% CI 1.27–1.80). A basic clinical prediction model was improved on addition of each biomarker individually, most strongly by NT-proBNP (NRI +62.3%, P &lt; 0.001), but thereafter was only improved marginally by addition of hsTnT (NRI +33.1%, P = 0.004). Further addition of biomarkers did not improve discrimination further. Findings were similar for all-cause mortality. Conclusion: Once NT-proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT-proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome