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      Early Trends in Cystatin C and Outcomes in Patients with Cirrhosis and Acute Kidney Injury

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          Abstract

          Background. Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35%) met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36%) (Scr−/CysC−); only cystatin increased 25 (24%) (Scr−/CysC+); only creatinine increased 15 (14%) (Scr+/CysC−); and both increased 28 (26%) (Scr+/CysC+). With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, P = 0.02 and 0.03, respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes.

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          Early detection of acute renal failure by serum cystatin C.

          Acute renal failure (ARF) is associated with high mortality. Presently, no specific therapy for ARF exists. Therefore, early detection of ARF is critical to prevent its progression. However, serum creatinine, the standard marker to detect ARF, demonstrates major limitations. We prospectively evaluated whether serum cystatin C detected ARF earlier than serum creatinine. In 85 patients at high risk to develop ARF, serum creatinine and cystatin C were determined daily. ARF was defined according to the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and ESRD (RIFLE) classification when creatinine increased by >/=50% (R-criteria), by >/=100% (I-criteria), or by >/=200% (F-criteria). In analogy, ARF was detected when cystatin C increased by >/=50%, by >/=100%, or by >/=200%. Forty-four patients developed ARF and 41 served as controls. In ARF by R-, I-, and F-criteria, the increase of cystatin C significantly preceded that of creatinine. Specifically, serum cystatin C increased already by >/=50% 1.5 +/- 0.6 days earlier compared to creatinine. Serum cystatin C demonstrated a high diagnostic value to detect ARF as indicated by area under the curve of the ROC analysis of 0.82 and 0.97 on the two days before the R-criteria was fulfilled by creatinine. Cystatin C detected ARF according to the R-criteria with a sensitivity of 55% and 82% on these days, respectively. Cystatin C also performed excellently, detecting ARF defined by the I- and F-criteria two days prior to creatinine, and moderately well predicting renal replacement therapy in the further course of ARF. Additionally, low T(3)- or T(3)/T(4) syndrome, glucocorticoid deficiency and excess did not affect cystatin C levels, adding to its usefulness in critically ill patients with ARF. Serum cystatin C is a useful detection marker of ARF, and may detect ARF one to two days earlier than creatinine.
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            Association of AKI with mortality and complications in hospitalized patients with cirrhosis.

            Acute kidney injury (AKI) is a common and devastating complication in patients with cirrhosis. However, the definitions of AKI employed in studies involving patients with cirrhosis have not been standardized, lack sensitivity, and are often limited to narrow clinical settings. We conducted a multicenter, prospective observational cohort study of patients with cirrhosis and AKI, drawn from multiple hospital wards, utilizing the modern acute kidney injury network (AKIN) definition and assessed the association between AKI severity and progression with in-hospital mortality. Of the 192 patients who were enrolled and included in the study, 85 (44%) progressed to a higher AKIN stage after initially fulfilling AKI criteria. Patients achieved a peak severity of AKIN stage 1, 26%, stage 2, 24%, and stage 3, 49%. The incidence of mortality, general medical events (bacteremia, pneumonia, urinary tract infection), and cirrhosis-specific complications (ascites, encephalopathy, spontaneous bacterial peritonitis) increased with severity of AKI. Progression was significantly more common and peak AKI stage higher in nonsurvivors than survivors (P < 0.0001). After adjusting for baseline renal function, demographics, and critical hospital- and cirrhosis-associated variables, progression of AKI was independently associated with mortality (adjusted odds ratio = 3.8, 95% confidence interval 1.3-11.1).
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              Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery--a prospective cohort study.

              To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury (AKI) in adult cardiac surgical patients according to preoperative renal function. Single-center, prospective observational study. Tertiary hospital. One hundred adult cardiac surgical patients. We measured concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C, and creatinine and urea at baseline, on arrival in the intensive care unit (ICU) and at 24 hours postoperatively. We assessed such biomarkers in relation to the development of AKI (>50% increase in creatinine from baseline) and to a composite end point (need for renal replacement therapy and in-hospital mortality). We defined an area under the receiver operating characteristic curve of 0.60-0.69 as poor, 0.70-0.79 as fair, 0.80-0.89 as good, and 0.90-1.00 as excellent in terms of predictive value. On arrival in ICU, plasma NGAL and serum cystatin C were of good predictive value, but creatinine and urea were of poor predictive value. After exclusion of patients with preoperative renal impairment (estimated glomerular filtration rate <60 mL/min), the predictive performance for AKI of all renal biomarkers on arrival in ICU remained unchanged except for cystatin C, which was of fair value in such patients. At 24 hours postoperatively, all renal biomarkers were of good predictive value. On arrival in ICU, novel biomarkers were superior to conventional biomarkers (p < 0.05). Plasma NGAL (p = 0.015) and serum cystatin C (p = 0.007) were independent predictors of AKI and of excellent value in the prediction of the composite end point. Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery. Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting.
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                Author and article information

                Journal
                Int J Nephrol
                Int J Nephrol
                IJN
                International Journal of Nephrology
                Hindawi Publishing Corporation
                2090-214X
                2090-2158
                2014
                18 March 2014
                : 2014
                : 708585
                Affiliations
                1Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT 06510, USA
                2Section of Nephrology, Yale University School of Medicine, New Haven, CT 06520, USA
                3Clinical Epidemiology Research Center, VAMC, West Haven, CT 06516, USA
                4Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
                5Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
                6VA-Connecticut Healthcare System, West Haven, CT 06520, USA
                7Division of Nephrology, Department of Internal Medicine, Jacobi Medical Center, South Bronx, NY 10461, USA
                8Division of General Internal Medicine, San Francisco VA Medical Center, University of California, San Francisco, CA 94121, USA
                Author notes

                Academic Editor: Jaime Uribarri

                Author information
                http://orcid.org/0000-0001-7468-8432
                Article
                10.1155/2014/708585
                3976933
                24757564
                2b560c46-b80d-40ec-88ee-9920d8165688
                Copyright © 2014 Justin M. Belcher et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 December 2013
                : 10 February 2014
                : 10 February 2014
                Funding
                Funded by: http://dx.doi.org/10.13039/100000062 National Institute of Diabetes and Digestive and Kidney Diseases
                Award ID: 1R21-DK078714
                Funded by: http://dx.doi.org/10.13039/100000002 National Institutes of Health
                Award ID: P-30DK034989
                Categories
                Research Article

                Nephrology
                Nephrology

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