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      Safety and Efficacy of Tolvaptan for the Prevention of Contrast-Induced Acute Kidney Injury in Patients with Heart Failure and Chronic Kidney Disease

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          Abstract

          Background

          Tolvaptan is a promising drug for the prevention of contrast-induced acute kidney injury (CI-AKI) because it induces aquaresis without adversely affecting renal hemodynamics. CI-AKI is a major cause of acute renal failure associated with increased morbidity and mortality.

          Objective

          To investigate the effectiveness of different doses of tolvaptan for the prevention of CI-AKI.

          Method

          Ninety-one consecutive patients with congestive heart failure (CHF) and chronic kidney disease (CKD) were prospectively enrolled as the tolvaptan group in this study (T-group; 7.5-mg: n = 42, 15-mg: n = 49). In addition, 91 consecutive patients with CHF and CKD were collected retrospectively as a control group (C-group, n = 91). All patients received continuous intravenous infusion of isotonic saline, and tolvaptan was administered to the T-group.

          Results

          One patient developed CI-AKI in the T-group versus 3 in the C-group (1.1 vs. 3.3%, p = 0.61). On the other hand, the change of serum creatinine in the T-group was lower than that in the C-group. Additionally, in the 7.5-mg group, serum creatinine was unchanged up to 72 h after contrast administration, showing a significant difference from the 15-mg group (–0.00 ± 0.09 vs. 0.05 ± 0.12 mg/dL, p = 0.009). Similarly, the change of eGFR was significantly smaller in the 7.5-mg group than that in the 15-mg group (0.7 ± 5.4 vs. −2.8 ± 5.1 mL/min/1.73 m 2, p = 0.002). No patient required hemodialysis and there was no prolongation of hospitalization due to exacerbation of heart failure.

          Conclusions

          Compared to hydration alone, tolvaptan combined with hydration could be a safer method for preventing CI-AKI while avoiding exacerbation of heart failure, and a dosage of 7.5-mg might be safer than 15-mg.

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          Most cited references20

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          A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.

          We sought to develop a simple risk score of contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI). Although several risk factors for CIN have been identified, the cumulative risk rendered by their combination is unknown. A total of 8,357 patients were randomly assigned to a development and a validation dataset. The baseline clinical and procedural characteristics of the 5,571 patients in the development dataset were considered as candidate univariate predictors of CIN (increase >or=25% and/or >or=0.5 mg/dl in serum creatinine at 48 h after PCI vs. baseline). Multivariate logistic regression was then used to identify independent predictors of CIN with a p value 75 years, anemia, and volume of contrast) were assigned a weighted integer; the sum of the integers was a total risk score for each patient. The overall occurrence of CIN in the development set was 13.1% (range 7.5% to 57.3% for a low [ or=16] risk score, respectively); the rate of CIN increased exponentially with increasing risk score (Cochran Armitage chi-square, p < 0.0001). In the 2,786 patients of the validation dataset, the model demonstrated good discriminative power (c statistic = 0.67); the increasing risk score was again strongly associated with CIN (range 8.4% to 55.9% for a low and high risk score, respectively). The risk of CIN after PCI can be simply assessed using readily available information. This risk score can be used for both clinical and investigational purposes.
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            Contrast-induced acute kidney injury.

            Cardiac angiography and coronary/vascular interventions depend on iodinated contrast media and consequently pose the risk of contrast-induced acute kidney injury (AKI). This is an important complication that accounts for a significant number of cases of hospital-acquired renal failure, with adverse effects on prognosis and health care costs. The epidemiology and pathogenesis of contrast-induced AKI, baseline renal function measurement, risk assessment, identification of high-risk patients, contrast medium use, and preventive strategies are discussed in this report. An advanced algorithm is suggested for the risk stratification and management of contrast-induced AKI as it relates to patients undergoing cardiovascular procedures. Contrast-induced AKI is likely to remain a significant challenge for cardiologists in the future because the patient population is aging and chronic kidney disease and diabetes are becoming more common.
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              Pathophysiology of contrast medium-induced nephropathy.

              Contrast medium-induced nephropathy (CIN) is a well-known cause of acute renal failure, but the development of CIN remains poorly understood. A number of studies have been performed with the one aim, to shed some light onto the pathophysiology of CIN. These have led to manifold interpretations and sometimes contradicting conclusions. This review critically surveys mechanisms believed to mediate CIN by highlighting the complex pathophysiologic entity, including altered rheologic properties, perturbation of renal hemodynamics, regional hypoxia, auto- and paracrine factors [adenosine, endothelin, and reactive oxygen species (ROS)], and direct cytotoxic effects. Moreover, the importance of physicochemical properties of contrast media are made clear. The more recently developed iso-osmolar contrast media are dimers, not monomers as the widely used nonionic low osmolar contrast media. The dimers have physicochemical features different from other contrast media which may be of clinical importance, not only with respect to osmolality. The viscosity of the commercially available dimers is considerably higher than blood. Many experimental studies provide evidence for a greater perturbation in renal functions by dimeric contrast media in comparison to nonionic monomeric contrast media. Clinical trials have yielded conflicting results.
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                Author and article information

                Journal
                Kidney Dis (Basel)
                Kidney Dis (Basel)
                KDD
                Kidney Diseases
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH-4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )
                2296-9381
                2296-9357
                March 2019
                29 November 2018
                1 March 2020
                : 5
                : 2
                : 100-106
                Affiliations
                Division of Cardiology and Cardiac Catheterization Laboratories, Showa University Northern Yokohama Hospital, Yokohama, Japan
                Author notes
                *Kennosuke Yamashita, MD, PhD, Division of Cardiology and Cardiac Catheterization Laboratories, Showa University Northern Yokohama Hospital, 35-1 Chigasaki-chuo, Tsuzuki-ku, Yokohama, Kanagawa 224-0032 (Japan), E-Mail kennosuke.atmm3@ 123456gmail.com
                Article
                PMC6465699 PMC6465699 6465699 kdd-0005-0100
                10.1159/000494724
                6465699
                31019923
                25461d0a-f4ec-4a67-85de-c40498602222
                Copyright © 2018 by S. Karger AG, Basel
                History
                : 3 August 2018
                : 19 October 2018
                : 2019
                Page count
                Figures: 1, Tables: 4, References: 25, Pages: 7
                Categories
                Research Article

                Heart failure,Tolvaptan,Contrast-induced acute kidney injury,Chronic kidney disease

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