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      Utility of Novel Cardiorenal Biomarkers in the Prediction and Early Detection of Congestive Kidney Injury Following Cardiac Surgery

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          Abstract

          Acute Kidney Injury (AKI) in the context of right ventricular failure (RVF) is thought to be largely congestive in nature. This study assessed the utility of biomarkers high sensitivity cardiac troponin T (hs-cTnT), N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and neutrophil gelatinase-associated lipocalin (NGAL) for prediction and early detection of congestive AKI (c-AKI) following cardiac surgery. This prospective nested case-control study recruited 350 consecutive patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. Cases were patients who developed (1) AKI (2) new or worsening RVF, or (3) c-AKI. Controls were patients free of these complications. Biomarker levels were measured at baseline after anesthesia induction and immediately postoperatively. Patients with c-AKI had increased mean duration of mechanical ventilation and length of stay in hospital and in the intensive care unit ( p < 0.01). For prediction of c-AKI, baseline NT-proBNP yielded an area under the curve (AUC) of 0.74 (95% CI, 0.60–0.89). For early detection of c-AKI, postoperative NT-proBNP yielded an AUC of 0.78 (0.66–0.91), postoperative hs-cTnT yielded an AUC of 0.75 (0.58–0.92), and ∆hs-cTnT yielded an AUC of 0.80 (0.64–0.96). The addition of baseline creatinine to ∆hs-cTnT improved the AUC to 0.87 (0.76–0.99), and addition of diabetes improved the AUC to 0.93 (0.88–0.99). Δhs-cTnT alone, or in combination with baseline creatinine or diabetes, detects c-AKI with high accuracy following cardiac surgery.

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          Importance of venous congestion for worsening of renal function in advanced decompensated heart failure.

          To determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function (WRF) in patients with advanced decompensated heart failure (ADHF). Reduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF. A total of 145 consecutive patients admitted with ADHF treated with intensive medical therapy guided by pulmonary artery catheter were studied. We defined WRF as an increase of serum creatinine >/=0.3 mg/dl during hospitalization. In the study cohort (age 57 +/- 14 years, cardiac index 1.9 +/- 0.6 l/min/m(2), left ventricular ejection fraction 20 +/- 8%, serum creatinine 1.7 +/- 0.9 mg/dl), 58 patients (40%) developed WRF. Patients who developed WRF had a greater central venous pressure (CVP) on admission (18 +/- 7 mm Hg vs. 12 +/- 6 mm Hg, p < 0.001) and after intensive medical therapy (11 +/- 8 mm Hg vs. 8 +/- 5 mm Hg, p = 0.04). The development of WRF occurred less frequently in patients who achieved a CVP <8 mm Hg (p = 0.01). Furthermore, the ability of CVP to stratify risk for development of WRF was apparent across the spectrum of systemic blood pressure, pulmonary capillary wedge pressure, cardiac index, and estimated glomerular filtration rates. Venous congestion is the most important hemodynamic factor driving WRF in decompensated patients with advanced heart failure.
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            Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares.

            Central venous pressure (CVP) is used almost universally to guide fluid therapy in hospitalized patients. Both historical and recent data suggest that this approach may be flawed. A systematic review of the literature to determine the following: (1) the relationship between CVP and blood volume, (2) the ability of CVP to predict fluid responsiveness, and (3) the ability of the change in CVP (DeltaCVP) to predict fluid responsiveness. MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. Reported clinical trials that evaluated either the relationship between CVP and blood volume or reported the associated between CVP/DeltaCVP and the change in stroke volume/cardiac index following a fluid challenge. From 213 articles screened, 24 studies met our inclusion criteria and were included for data extraction. The studies included human adult subjects, healthy control subjects, and ICU and operating room patients. Data were abstracted on study design, study size, study setting, patient population, correlation coefficient between CVP and blood volume, correlation coefficient (or receive operator characteristic [ROC]) between CVP/DeltaCVP and change in stroke index/cardiac index, percentage of patients who responded to a fluid challenge, and baseline CVP of the fluid responders and nonresponders. Metaanalytic techniques were used to pool data. The 24 studies included 803 patients; 5 studies compared CVP with measured circulating blood volume, while 19 studies determined the relationship between CVP/DeltaCVP and change in cardiac performance following a fluid challenge. The pooled correlation coefficient between CVP and measured blood volume was 0.16 (95% confidence interval [CI], 0.03 to 0.28). Overall, 56+/-16% of the patients included in this review responded to a fluid challenge. The pooled correlation coefficient between baseline CVP and change in stroke index/cardiac index was 0.18 (95% CI, 0.08 to 0.28). The pooled area under the ROC curve was 0.56 (95% CI, 0.51 to 0.61). The pooled correlation between DeltaCVP and change in stroke index/cardiac index was 0.11 (95% CI, 0.015 to 0.21). Baseline CVP was 8.7+/-2.32 mm Hg [mean+/-SD] in the responders as compared to 9.7+/-2.2 mm Hg in nonresponders (not significant). This systematic review demonstrated a very poor relationship between CVP and blood volume as well as the inability of CVP/DeltaCVP to predict the hemodynamic response to a fluid challenge. CVP should not be used to make clinical decisions regarding fluid management.
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              Cardio-renal syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative

              A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF–ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                12 December 2018
                December 2018
                : 7
                : 12
                : 540
                Affiliations
                [1 ]Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H8M5, Canada; jzelt@ 123456ottawaheart.ca (J.G.E.Z.); LMielniczuk@ 123456ottawaheart.ca (L.M.M.)
                [2 ]Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, 40 Ruskin Street Ottawa, ON K1Y 4W7, Canada; pliu@ 123456ottawaheart.ca (P.P.L.); schih@ 123456ottawaheart.ca (S.C.)
                [3 ]Division of Nephrology, Department of Medicine, The Ottawa Hospital, 1967 Riverside Dr., Ottawa, ON K1H 7W9, Canada; aakbari@ 123456toh.ca
                [4 ]Division of Cardiac Anesthesiology, Department of Anesthesiology and Pain Medicine, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada; jydupuis@ 123456ottawaheart.ca
                [5 ]School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Crescent, Ottawa, ON K1G 5Z3, Canada
                Author notes
                [* ]Correspondence: lsun@ 123456ottawaheart.ca ; Tel.: +1-613-696-7381; Fax: +1-613-696-7099
                Article
                jcm-07-00540
                10.3390/jcm7120540
                6306702
                30545066
                0d244380-1df0-41bb-9d48-3714818e2402
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 November 2018
                : 10 December 2018
                Categories
                Article

                cardiac surgery,biomarkers,right heart failure,congestive acute kidney injury,venous congestion

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