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      Renal resistive index as an early predictor and discriminator of acute kidney injury in critically ill patients; A prospective observational cohort study

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          Abstract

          Background

          Acute kidney injury (AKI) complicates shock. Diagnosis is based on rising creatinine, a late phenomenon. Intrarenal vasoconstriction occurs earlier. Measuring flow resistance in the renal circulation, Renal Resistive Index (RRI), could become part of vital organ function assessment using Doppler ultrasound. Our aim was to determine whether RRI on ICU admission is an early predictor and discriminator of AKI developed within the first week.

          Methods

          In this prospective cohort of mixed ICU patients with and without shock, RRI was measured <24-h of admission. Besides routine variables, sublingual microcirculation and bioelectrical impedance were measured. AKI was defined by the Kidney Disease Improving Global Outcomes criteria. Uni- and multivariate regression and Receiver Operating Characteristics curve analyses were performed.

          Results

          Ninety-nine patients were included, median age 67 years (IQR 59–75), APACHE III score 67 (IQR 53–89). Forty-nine patients (49%) developed AKI within the first week. AKI patients had a higher RRI on admission than those without: 0.71 (0.69–0.73) vs. 0.65 (0.63–0.68), p = 0.001. The difference was significant for AKI stage 2: RRI = 0.72 (0.65–0.80) and 3: RRI = 0.74 (0.67–0.81), but not for AKI stage 1: RRI = 0.67 (0.61–0.74). On univariate analysis, RRI significantly predicted AKI 2–3: OR 1.012 (1.006–1.019); Area Under the Curve (AUC) of RRI for AKI 2–3 was 0.72 (0.61–0.83), optimal cut-off 0.74, sensitivity 53% and specificity 87%. On multivariate analysis, RRI remained significant, independent of APACHE III and fluid balance; adjusted OR: 1.008 (1.000–1.016).

          Conclusions

          High RRI on ICU admission was a significant predictor for development of AKI stage 2–3 during the first week. High RRI can be used as an early warning signal RRI, because of its high specificity. A combined score including RRI, APACHE III and fluid balance improved AKI prediction, suggesting that vasoconstriction or poor vascular compliance, severity of disease and positive fluid balance independently contribute to AKI development.

          Trial registration

          ClinicalTrials.gov NCT02558166.

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          Most cited references50

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          Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.

          The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.
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            The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults.

            The objective of this study was to refine the APACHE (Acute Physiology, Age, Chronic Health Evaluation) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults. We prospectively collected data on 17,440 unselected adult medical/surgical intensive care unit (ICU) admissions at 40 US hospitals (14 volunteer tertiary-care institutions and 26 hospitals randomly chosen to represent intensive care services nationwide). We analyzed the relationship between the patient's likelihood of surviving to hospital discharge and the following predictive variables: major medical and surgical disease categories, acute physiologic abnormalities, age, preexisting functional limitations, major comorbidities, and treatment location immediately prior to ICU admission. The APACHE III prognostic system consists of two options: (1) an APACHE III score, which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups; and (2) an APACHE III predictive equation, which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients. A five-point increase in APACHE III score (range, 0 to 299) is independently associated with a statistically significant increase in the relative risk of hospital death (odds ratio, 1.10 to 1.78) within each of 78 major medical and surgical disease categories. The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h of ICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed (r2 = 0.41; receiver operating characteristic = 0.90). Recording changes in the APACHE III score on each subsequent day of ICU therapy provided daily updates in these risk estimates. When applied across the individual ICUs, the first-day APACHE III equation accounted for the majority of variation in observed death rates (r2 = 0.90, p less than 0.0001).
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              Pathophysiology of acute kidney injury.

              Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia, or nephrotoxicity. An underlying feature is a rapid decline in glomerular filtration rate (GFR) usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or chronic kidney disease (CKD) patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. © 2012 American Physiological Society. Compr Physiol 2:1303-1353, 2012.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draft
                Role: InvestigationRole: Project administrationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 June 2018
                2018
                : 13
                : 6
                : e0197967
                Affiliations
                [001]Department of Intensive Care Medicine, VU University Medical Center, Amsterdam, The Netherlands
                University of Sao Paulo Medical School, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-3035-0736
                http://orcid.org/0000-0002-1185-4373
                Article
                PONE-D-18-02047
                10.1371/journal.pone.0197967
                5995360
                29889830
                fdffc3b0-392e-4bef-a69e-3106722fea6f
                © 2018 Haitsma Mulier et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 January 2018
                : 5 May 2018
                Page count
                Figures: 3, Tables: 5, Pages: 18
                Funding
                The authors received no funding for this work. The department of Intensive Care Medicine of the VU medical center Amsterdam provided study materials. The authors performed analysis and wrote the article in line with their duties as medical students, researchers/employees of university healthcare institutions without receiving any financial compensation.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Creatinine
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Intensive Care Units
                Biology and Life Sciences
                Physiology
                Cardiovascular Physiology
                Blood Circulation
                Microcirculation
                Medicine and Health Sciences
                Physiology
                Cardiovascular Physiology
                Blood Circulation
                Microcirculation
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Medicine and Health Sciences
                Pharmaceutics
                Dose Prediction Methods
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Amines
                Catecholamines
                Norepinephrine
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Amines
                Catecholamines
                Norepinephrine
                Biology and Life Sciences
                Biochemistry
                Neurochemistry
                Neurotransmitters
                Biogenic Amines
                Catecholamines
                Norepinephrine
                Biology and Life Sciences
                Neuroscience
                Neurochemistry
                Neurotransmitters
                Biogenic Amines
                Catecholamines
                Norepinephrine
                Biology and Life Sciences
                Biochemistry
                Hormones
                Catecholamines
                Norepinephrine
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Ultrasound Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Ultrasound Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Ultrasound Imaging
                Custom metadata
                The de-identified study data from the RRI AKI study are freely accessible without restrictions. The dataset was uploaded to the Harvard Dataverse database, DOI: https://doi.org/10.7910/DVN/IKAFNN.

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