A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Why Should We Preserve Fishless High Mountain Lakes?

High mountain lakes are originally fishless, although many have had introductions of non-native fish species, predominantly trout, and recently also minnows introduced by fishermen that use them as live bait. The extent of these introductions is general and substantial often involving many lakes over mountain ranges. Predation on native fauna by introduced fish involves profound ecological changes since fish occupy a higher trophic level that was previously inexistent. Fish predation produces a drastic reduction or elimination of autochthonous animal groups, such as amphibians and large macroinvertebrates in the littoral, and crustaceans in the plankton. These strong effects raise concerns for the conservation of high mountain lakes. In terms of individual species, those adapted to live in larger lakes have suffered a higher decrease in the size of their metapopulation. This ecological problem is discussed from a European perspective providing examples from two study areas: the Pyrenees and the Western Italian Alps. Species-specific studies are urgently needed to evaluate the conservation status of the more impacted species, together with conservation measures at continental and regional scales, through regulation, and at local scale, through restoration actions, aimed to stop further invasive species expansions and to restore the present situation. At different high mountain areas of the world, there have been restoration projects aiming to return lakes to their native fish-free status. In these areas autochthonous species that disappeared with the introduction of fish are progressively recovering their initial distribution when nearby fish-free lakes and ponds are available

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD

Abstract BACKGROUND AND OBJECTIVES: Soluble TNF-like weak inducer of apoptosis (sTWEAK) is a proinflammatory cytokine belonging to the TNF superfamily. sTWEAK concentrations have been associated with the presence of CKD and cardiovascular disease (CVD). We hypothesized that sTWEAK levels may relate to a higher prevalence of atherosclerotic plaques, vascular calcification, and cardiovascular outcomes observed in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A 4-year prospective, multicenter, longitudinal study was conducted in 1058 patients with CKD stages 3-5D (mean age =58±13 years old; 665 men) but without any history of CVD from the NEFRONA Study (a study design on the prevalence of surrogate markers of CVD). Ankle-brachial index and B-mode ultrasound were performed to detect the presence of carotid and/or femoral atherosclerotic plaques together with biochemical measurements and sTWEAK assessment. Patients were followed for cardiovascular outcomes (follow-up of 3.13±1.15 years). RESULTS: Patients with more advanced CKD had lower sTWEAK levels. sTWEAK concentrations were independently and negatively associated with carotid intima-media thickness. sTWEAK levels were lower in patients with carotid atherosclerotic plaques but not in those with femoral plaques. After adjustment by confounders, the odds ratio (OR) for presenting carotid atherosclerotic plaques in patients in the lowest versus highest tertile of sTWEAK was 4.18 (95% confidence interval [95% CI], 2.89 to 6.08; P<0.001). Furthermore, sTWEAK levels were lower in patients with calcified carotid atherosclerotic plaques. The OR for presenting calcified carotid plaques was 1.77 (95% CI, 1.06 to 2.93; P=0.02) after multivariable adjustment. After the follow-up, 41 fatal and 68 nonfatal cardiovascular events occurred. In a Cox model, after controlling for potential confounding factors, patients in the lowest tertile of sTWEAK concentrations had a higher risk of fatal and nonfatal cardiovascular events (hazard ratio [HR], 2.40; 95% CI, 1.33 to 4.33; P=0.004) and cardiovascular mortality (HR, 2.67; 95% CI, 1.05 to 6.76; P=0.04). CONCLUSIONS: Low sTWEAK levels were associated with the presence of carotid atherosclerotic plaques in patients with CKD. Additionally, lower sTWEAK levels were associated with a higher risk of cardiovascular morbidity and mortality

Soluble TWEAK and atheromatosis progression in patients with chronic kidney disease

BACKGROUND AND AIMS: Circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) concentrations are related to the presence of chronic kidney disease (CKD) and cardiovascular disease (CVD). However, there are no data regarding the potential association between sTWEAK and atheromatosis progression in patients free of cardiovascular events. METHODS: Soluble TWEAK serum concentration was measured in 702 CKD patients without any previous CV event from The National Observatory of Atherosclerosis in Nephrology (NEFRONA) Study. B-mode ultrasound was performed to detect the presence of carotid and/or femoral atherosclerotic plaques. The association between sTWEAK levels, atherosclerotic burden (number of plaques) and atheromatosis progression (increase in the number of plaques) after 24 months of follow-up was analyzed. RESULTS: A continuous decrease in sTWEAK concentrations, with an increase in the number of atherosclerotic plaques after 24 months of follow-up, was observed in the studied population. Multivariable linear regression analysis showed that age, blood pressure, HDL-c, and sTWEAK concentrations were independent predictors of atherosclerotic burden after 24 months of follow-up. In addition, sTWEAK concentrations diminished in CKD patients in whom progressive silent atherosclerosis was observed. Multivariable linear regression analysis showed that age, sex, smoking status and sTWEAK levels were independent predictors of atheromatosis progression after 24 months of follow-up. CONCLUSIONS: Lower sTWEAK concentrations are associated with atherosclerotic burden and atheromatosis progression in CKD patients free of clinical CVD. These data suggest that sTWEAK could serve as a biomarker to predict CV risk before clinical manifestations