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      Can Serum Cystatin C predict long-term survival in cardiac surgery patients?

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          Abstract

          Renal dysfunction is a risk factor for morbidity and mortality in cardiac surgery patients. Serum Cystatin C (sCysC) is a well-recognized marker of early renal dysfunction but few reports evaluate its prognostic cardio-vascular role. The aim of the study is to consider the prognostic value of sCysC for cardiovascular mortality. Four hundred twenty-four cardiac-surgery patients (264 men and 160 women) were enrolled. At admission, all patients were tested for renal function and inflammatory status. Patients were subdivided in subgroups according to the values of the following variables: sCysC, serum Creatinine (sCrea), age, high sensitivity-C Reactive Protein, fibrinogen, surgical procedures and Kaplan-Meier cumulative survival curves were plotted. The primary end-point was cardiovascular mortality. In order to evaluate the simultaneous independent impact of all measured variables on survival we fitted a multivariate Cox-Proportional Hazard Model (CPHM). In Kaplan-Meier analysis 124 patients (29.4%) reached the end-point. In multivariate CPHM, the only significant predictors of mortality were sCysC (p<0.00001, risk ratio: 1.529, CI: 1.29-1.80) and age (p=0.039, risk ratio: 1.019, CI: 1.001-1.037). When replacing sCysC with sCrea, the only significant predictor of mortality was sCrea (p=0.0026; risk ratio 1.20; CI: 1.06-1.36). Increased levels of sCysC can be considered a useful biomarker of cardiovascular mortality in cardiac-surgery patients.

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          Biomarkers of renal function, which and when?

          Acute kidney injury (AKI) and chronic kidney disease (CKD) are conditions that substantially increase morbidity and mortality. Although novel biomarkers are being used in practice, the diagnosis of AKI and CKD is still made with surrogate markers of GFR, such as serum creatinine (SCr), urine output and creatinine based estimating equations. SCr is limited as a marker of kidney dysfunction in both settings and may be inaccurate in several situations, such as in patients with low muscle mass or with fluid overload. New biomarkers have the potential to identify earlier patients with AKI and CKD and in the future potentially intervene to modify outcomes.
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            Incidence and outcomes of acute kidney injury after cardiac surgery using either criteria of the RIFLE classification

            Background Adult cardiac surgery is significantly associated with the development of acute kidney injury (AKI). Still, the incidence and outcomes of AKI vary according to its definition. Our retrospective monocentric study comparatively investigates the yield of RIFLE definition, which is based on the elevation of serum creatinine levels (SCr) or the reduction of urine output (UO), taking into account only one or both criteria. Pre- and per-operative risk factors for post-operative AKI were evaluated. Methods All adult patients undergoing cardiac surgery, with or without cardiopulmonary bypass, from April 2008 to March 2009 were included. Clinical, biological and surgical features were recorded. Baseline serum creatinine was determined as its value on day 7 before surgery. Post-operative AKI was diagnosed and scored based upon the highest serum creatinine and/or the lowest urine output. Results 443 patients (Male/Female ratio, 2.3; median age, 69y) were included, with 221 (49.9 %) developing postoperative AKI. Elevated serum creatinine (AKISCr) and oliguria (AKIUO) was observed in 9.7 % and 40.2 %, respectively. AKI patients had a significantly higher BMI and baseline SCr. In comparison to AKIUO, AKISCr mostly occurred in patients with co-morbidities, and was associated with an increased mortality at 1-year post surgery. Conclusions The use of standard RIFLE definition of AKI in a cohort of 443 patients undergoing cardiac surgery resulted in an incidence reaching 50 %. Still, significant discrepancies were found between AKISCr and AKIUO regarding the incidence and outcomes. In line with previous reports, our data questions the utility of urine output as a criterion for AKI diagnosis and management after cardiac surgery.
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              Cystatin C and cardiovascular risk.

              Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular disease (CVD) and cardiovascular events. Cystatin C, a protease inhibitor synthesized in all nucleated cells, has been proposed as a replacement for serum creatinine for the assessment of renal function, particularly to detect small reductions in glomerular filtration rate. This report presents a review of the role of cystatin C as a predictor of cardiovascular risk. Patients with higher circulating cystatin C concentrations appear to have an increased cardiovascular risk profile, i.e., they are older and have a higher prevalence of systemic hypertension, dyslipidemia, documented CVD, increased body mass index, and increased concentrations of C-reactive protein. Prospective studies have shown, in various clinical scenarios, that patients with increased cystatin C are at a higher risk of developing both CVD and CKD. Importantly, cystatin C appears to be a useful marker for identifying individuals at a higher risk for cardiovascular events among patients belonging to a relatively low-risk category as assessed by both creatinine and estimated glomerular filtration rate values. Of interest, elastolytic proteases and their inhibitors, in particular cystatin C, have been shown to be directly involved in the atherosclerotic process. Increased concentrations of cystatin C appear to be indicative of preclinical kidney disease associated with adverse outcomes. Clinical studies involving direct glomerular filtration rate measurements are required to ascertain both the true role of this promising marker in renal disease and whether atherogenic factors like inflammation can account for increases in cystatin C concentrations, thus explaining its predictive value in CVD.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                March 2018
                27 March 2018
                : 10
                : 3
                : 425-433
                Affiliations
                [1 ]Department of Medicine, Hypertension and Nephrology Unit, University Hospital Tor Vergata , Rome, 00133, Italy
                [2 ]PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata , Rome, 00133, Italy
                [3 ]Department of Laboratory Medicine, University Hospital Tor Vergata , Rome, 00133, Italy
                [4 ]Department of Biomedicine and Prevention, Medical Physics Section, University of Rome Tor Vergata , Rome, 00133, Italy
                Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging and Harvard Medical School , Boston, , MA, 02129, USA
                Department of Cardiac Surgery, University Hospital Tor Vergata, Rome 00133, Italy,
                [7 ]Federazione Medico Sportiva Italiana, Rome, 00196, Italy
                Author notes
                Correspondence to: Valentina Rovella; email: valerovix@ 123456yahoo.it
                Annalisa Noce; email: annalisa.noce@ 123456uniroma2.it
                Article
                101403
                10.18632/aging.101403
                5892696
                29615540
                335c7f52-8748-4ba3-b925-0dd87a2890c9
                Copyright © 2018 Rovella et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 January 2018
                : 16 March 2018
                Categories
                Research Paper

                Cell biology
                serum cystatin c,cardio-vascular mortality,serum creatinine,risk stratification,cardiac surgery,cardiovascular biomarker

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