ORCID Profile
0000-0003-1995-2653
Current Organisations
National Resarch Centre for the Working Environment
,
University of Pittsburgh
,
University of Manchester
,
University College London
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Medical Association (AMA)
Date: 20-11-2018
Publisher: S. Karger AG
Date: 26-05-2020
DOI: 10.1159/000508125
Abstract: Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems. In the absence of vaccines or direct therapy for COVID-19, extracorporeal therapies could represent an option to prevent organ failure and improve survival. The enormous demand in care for COVID-19 patients requires an immediate response from the scientific community. Thus, a detailed review of the available technology is provided by experts followed by a series of recommendation based on current experience and opinions, while waiting for generation of robust evidence from trials.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2008
DOI: 10.2215/CJN.03830907
Publisher: Oxford University Press (OUP)
Date: 06-04-2009
DOI: 10.1093/NDT/GFP159
Abstract: The RIFLE classification scheme for acute kidney injury (AKI) is based on relative changes in serum creatinine (SCr) and on urine output. The SCr criteria, therefore, require a pre-morbid baseline value. When unknown, current recommendations are to estimate a baseline SCr by the MDRD equation. However, the MDRD approach assumes a glomerular filtration rate of approximately 75 mL/min/1.73 m(2). This method has not been validated. Data from the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study, a prospective observational study from 54 ICUs in 23 countries of critically ill patients with severe AKI, were analysed. The RIFLE class was determined by using observed (o) pre-morbid and estimated (e) baseline SCr values. Agreement was evaluated by correlation coefficients and Bland-Altman plots. Sensitivity analysis by chronic kidney disease (CKD) status was performed. Seventy-six percent of patients (n = 1327) had a pre-morbid baseline SCr, and 1314 had complete data for evaluation. Forty-six percent had CKD. The median (IQR) values were 97 micromol/L (79-150) for oSCr and 88 micromol/L (71-97) for eSCr. The oSCr and eSCr determined at ICU admission and at study enrolment showed only a modest correlation (r = 0.49, r = 0.39). At ICU admission and study enrolment, eSCr misclassified 18.8% and 11.7% of patients as having AKI compared with oSCr. Exclusion of CKD patients improved the correlation between oSCr and eSCr at ICU admission and study enrolment (r = 0.90, r = 0.84) resulting in 6.6% and 4.0% being misclassified, respectively. While limited, estimating baseline SCr by the MDRD equation when pre-morbid SCr is unavailable would appear to perform reasonably well for determining the RIFLE categories only if and when pre-morbid GFR was near normal. However, in patients with suspected CKD, the use of MDRD to estimate baseline SCr overestimates the incidence of AKI and should not likely be used. Improved methods to estimate baseline SCr are needed.
Publisher: S. Karger AG
Date: 18-09-2008
DOI: 10.1159/000142926
Abstract: Changes in urine output and glomerular filtration rate are neither necessary nor sufficient for the diagnosis of renal pathology. Yet no simple alternative for the diagnosis currently exists. Until recently, there has been no consensus as to diagnostic criteria or clinical definition of acute renal failure. Depending on the definition used, acute renal failure has been reported to affect from 1 to 25% of ICU patients and has led to mortality rates from 15 to 60%. The RIFLE criteria were developed to standardize the diagnosis of acute renal failure and in the process the term acute kidney injury (AKI) has been proposed to encompass the entire spectrum of the syndrome from minor changes in renal function to requirement for renal replacement therapy. Thus, AKI is not acute renal failure but a more general description. Small changes in kidney function in hospitalized patients are important and are associated with significant changes in short and possibly long-term outcomes. The RIFLE criteria provide a uniform definition of AKI and have now been validated in numerous studies.
Publisher: Springer Science and Business Media LLC
Date: 31-08-2023
Publisher: American Medical Association (AMA)
Date: 17-08-2005
Abstract: Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world. To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries to characterize differences in etiology, illness severity, and clinical practice and to determine the impact of these differences on patient outcomes. Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries. Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality. Of 29 269 critically ill patients admitted during the study period, 1738 (5.7% 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5% 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95 95% CI, 1.50-2.55 P<.001), mechanical ventilation (OR, 2.11 95% CI, 1.58-2.82 P<.001), septic shock (OR, 1.36 95% CI, 1.03-1.79 P = .03), cardiogenic shock (OR, 1.41 95% CI, 1.05-1.90 P = .02), and hepatorenal syndrome (OR, 1.87 95% CI, 1.07-3.28 P = .03). In this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.
Publisher: Informa UK Limited
Date: 02-01-2018
Publisher: Massachusetts Medical Society
Date: 08-06-2017
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1038/KI.2013.374
Publisher: Elsevier BV
Date: 2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2018
Publisher: Springer Science and Business Media LLC
Date: 2011
DOI: 10.1186/CC10318
Publisher: S. Karger AG
Date: 2013
DOI: 10.1159/000349964
Abstract: Acute kidney injury (AKI) is a common but complex clinical syndrome with multiple etiologies. These etiologies target different sites and pathways within the kidney. Novel biomarkers of 'kidney damage' (which can be tubular or glomerular) can be used to diagnose AKI, even in the absence of an increase in serum creatinine or oliguria. These biomarkers of kidney damage can be combined with biomarkers of kidney function to facilitate classification of AKI. A comprehensive review of the literature was performed using the published methodology of the Acute Dialysis Quality Initiative (ADQI) working group and used to establish consensus statements regarding the use of biomarkers in the differential diagnosis of AKI. We recommend that the pathophysiological terms 'functional change' and 'kidney damage' be used in preference to the anatomical classification using the terms pre-renal, renal and post-renal AKI. We further recommend the use of both renal and non-renal biomarkers in establishing the specific cause of AKI as soon as possible after diagnosis. The presence of underlying CKD or of sepsis poses additional challenges in differential diagnosis, since these conditions alter both baseline biomarker excretion and biomarker performance. We recommend that biomarkers be validated within the clinical context in which they are to be used. Within that context, combinations of biomarkers may, in the future, allow differentiation of the site, mechanism and phase of injury.
Publisher: Oxford University Press (OUP)
Date: 23-11-2018
DOI: 10.1093/NDT/GFX308
Abstract: There is no consensus whether higher intensity dose renal replacement therapy (RRT) compared with standard intensity RRT has survival benefit and achieves better renal recovery in acute kidney injury (AKI). In an in idual patient data meta-analysis, we merged in idual patient data from randomized controlled trials (RCTs) comparing high with standard intensity RRT in intensive care unit patients with severe AKI. The primary outcome was all-cause mortality. The secondary outcome was renal recovery assessed as the proportion of patients who were RRT dependent at key trial endpoints and by time to the end of RRT dependence. Of the eight prospective RCTs assessing different RRT intensities, seven contributed in idual patient data (n = 3682) to the analysis. Mortality was similar between the two groups at 28 days [769/1884 (40.8%) and 744/1798 (41.4%), respectively P = 0.40] after randomization. However, more participants assigned to higher intensity therapy remained RRT dependent at the most common key study point of 28 days [e.g. 292/983 (29.7%) versus 235/943 (24.9%) relative risk 1.15 (95% confidence interval 1.00-1.33) P = 0.05]. Time to cessation of RRT through 28 days was longer in patients receiving higher intensity RRT (log-rank test P = 0.02) and when continuous renal replacement therapy was used as the initial modality of RRT (log-rank test P = 0.03). In severe AKI patients, higher intensity RRT does not affect mortality but appears to delay renal recovery. Australian New Zealand Clinical Trials Registry (ANZCTR) identifier ACTRN12615000394549 (www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615000394549).
Publisher: S. Karger AG
Date: 07-10-2020
DOI: 10.1159/000510556
Abstract: b i Introduction: /i /b In continuous renal replacement therapy (CRRT)-treated patients, a net ultrafiltration (NUF) rate & #x3e .75 mL/kg/h has been associated with increased mortality. However, there may be heterogeneity of effect of NUF rate on mortality, according to patient characteristics. b i Methods: /i /b To investigate the presence and impact of heterogeneity of effect, we performed a secondary analysis of the “Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy” (RENAL) trial. Exposure was NUF rate (weight-adjusted fluid volume removed per hour) stratified into tertiles (& #x3c .01 mL/kg/h 1.01–1.75 mL/kg/h or & #x3e .75 mL/kg/h). Primary outcome was 90-day mortality. Patients were clustered according to baseline characteristics. Heterogeneity of effect was assessed according to clusters and baseline edema and related to the additional impact of baseline cardiovascular Sequential Organ Failure Assessment (SOFA) score. We excluded patients with missing values for baseline weight and/or treatment duration. b i Results: /i /b We identified 2 clusters. The largest (cluster 1 i n /i = 941) included more severely ill patients, with more sepsis, more edema, and more vasopressor therapy (all i /i & #x3c 0.001). Compared to the middle tertile, the probability of harm was greater with the high tertile of NUF rate in patients in cluster 1 and in patients with baseline edema (probability of harm, cluster 1: 99.9% edema: 99.1%). Moreover, higher baseline cardiovascular SOFA score also increased mortality risk with both high and low compared to middle NUF rates in cluster 1 patients and in patients with edema. b i Conclusions: /i /b In CRRT patients, both high and low NUF rates may be harmful, especially in those with edema, sepsis, and greater illness severity. Cardiovascular SOFA scores modulate this association. Additional studies are needed to test these hypotheses, and targeted trials of NUF rates based on risk stratification appear justified. b i Trial Registration: /i /b ClinicalTrials.gov identifier: NCT00221013.
Publisher: Oxford University Press (OUP)
Date: 17-10-2015
DOI: 10.1093/NDT/GFU314
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1093/BJA/AEU301
Abstract: Fluid management during critical illness is a dynamic process that may be conceptualized as occurring in four phases: rescue, optimization, stabilization, and de-escalation (mobilization). The selection and administration of resuscitation fluids is one component of this complex physiological sequence directed at restoring depleted intravascular volume. Presently, the selection of i.v. fluid is usually dictated more by local practice patterns than by evidence. The debate on fluid choice has primarily focused on evaluating outcome differences between 'crystalloids vs colloids'. More recently, however, there is interest in examining outcome differences based on the chloride content of crystalloid solutions. New insights into the conventional Starling model of microvascular fluid exchange may explain that the efficacy of colloids in restoring and maintaining depleted intravascular volume is only moderately better than crystalloids. A number of investigator-initiated, high-quality, randomized controlled trials have demonstrated that modest improvements in short-term physiological endpoints with colloids have not translated into better patient-centred outcomes. In addition, there is substantial evidence that certain types of fluids may independently worsen patient-centred outcomes. These include hydroxyethyl starch and albumin solutions in selected patient populations. There is no evidence to support the use of other colloids. The use of balanced salt solutions in preference to 0.9% saline is supported by the absence of harm in large observational studies. However, there is no compelling randomized trial-based evidence demonstrating improved clinical outcomes with the use of balanced salt solutions compared with 0.9% saline at this time.
Publisher: S. Karger AG
Date: 2013
DOI: 10.1159/000349962
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2008
Publisher: Springer Science and Business Media LLC
Date: 11-07-2015
DOI: 10.1007/S00134-015-3934-7
Abstract: Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients. The Acute Kidney Injury-Epidemiologic Prospective Investigation (AKI-EPI) study was an international cross-sectional study performed in 97 centers on patients during the first week of ICU admission. We measured AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and outcomes at hospital discharge. A total of 1032 ICU patients out of 1802 [57.3% 95% confidence interval (CI) 55.0-59.6] had AKI. Increasing AKI severity was associated with hospital mortality when adjusted for other variables odds ratio of stage 1 = 1.679 (95% CI 0.890-3.169 p = 0.109), stage 2 = 2.945 (95% CI 1.382-6.276 p = 0.005), and stage 3 = 6.884 (95% CI 3.876-12.228 p < 0.001). Risk-adjusted rates of AKI and mortality were similar across the world. Patients developing AKI had worse kidney function at hospital discharge with estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) in 47.7% (95% CI 43.6-51.7) versus 14.8% (95% CI 11.9-18.2) in those without AKI, p < 0.001. This is the first multinational cross-sectional study on the epidemiology of AKI in ICU patients using the complete KDIGO criteria. We found that AKI occurred in more than half of ICU patients. Increasing AKI severity was associated with increased mortality, and AKI patients had worse renal function at the time of hospital discharge. Adjusted risks for AKI and mortality were similar across different continents and regions.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Publisher: American Thoracic Society
Date: 05-2021
Publisher: Springer Science and Business Media LLC
Date: 06-2022
DOI: 10.1038/S41591-022-01843-X
Abstract: Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence-supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-suggests that the current syndrome-based framework of critical illness should be reconsidered. Here we discuss recent findings from basic science and clinical research in critical care and explore how these might inform a new conceptual model of critical illness. De-emphasizing syndromes, we focus on the underlying biological changes that underpin critical illness states and that may be amenable to treatment. We hypothesize that such an approach will accelerate critical care research, leading to a richer understanding of the pathobiology of critical illness and of the key determinants of patient outcomes. This, in turn, will support the design of more effective clinical trials and inform a more precise and more effective practice at the bedside.
Publisher: Oxford University Press (OUP)
Date: 10-05-2019
DOI: 10.1093/NDT/GFZ087
Abstract: Etiologies for acute kidney injury (AKI) vary by geographic region and socioeconomic status. While considerable information is now available on AKI in the Americas, Europe and China, large comprehensive epidemiologic studies of AKI from Southeast Asia (SEA) are still lacking. The aim of this study was to investigate the rates and characteristics of AKI among intensive care unit (ICU) patients in Thailand. We conducted the largest prospective observational study of AKI in SEA. The data were serially collected on the first 28 days of ICU admission by registration in electronic web-based format. AKI status was defined by full Kidney Disease: Improving Global Outcome criteria. We used AKI occurrence as the clinical outcome and explored the impact of modifiable and non-modifiable risk factors on the development and progression of AKI. We enrolled 5476 patients from 17 ICU centres across Thailand from February 2013 to July 2015. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 2471 of 4668 patients (52.9%). Overall, the maximum AKI stage was Stage 1 in 7.5%, Stage 2 in 16.5% and Stage 3 in 28.9%. In the multivariable adjusted model, we found that older age, female sex, admission to a regional hospital, medical ICU, high body mass index, primary diagnosis of cardiovascular-related disease and infectious disease, higher Acute Physiology and Chronic Health Evaluation II, non-renal Sequential Organ Failure Assessment scores, underlying anemia and use of vasopressors were all independent risk factors for AKI development. In Thai ICUs, AKI is very common. Identification of risk factors of AKI development will help in the development of a prognostic scoring model for this population and should help in decision making for timely intervention, ultimately leading to better clinical outcomes.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1NA00133G
Abstract: This study reveals the dependence of GO uptake mechanism on its lateral dimensions. The main uptake mechanism of s-GO shifts from macropinocytosis (4 h) to clathrin-dependent endocytosis (24 h), mediated by upregulation of mTORC1/2 pathway.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2009
Publisher: Springer Science and Business Media LLC
Date: 2010
DOI: 10.1186/CC9052
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2010
DOI: 10.2215/CJN.09111209
Publisher: Oxford University Press (OUP)
Date: 07-04-2021
DOI: 10.1093/NDT/GFAA032
Abstract: In patients treated with continuous renal replacement therapy (CRRT), early net ultrafiltration (NUF) rates may be associated with differential outcomes. We tested whether higher early NUF rates are associated with increased mortality in CRRT patients. We performed a retrospective, observational study of all patients treated with CRRT within 14 days of intensive care unit admission. We defined the early (first 48 h) NUF rate as the volume of fluid removed per hour adjusted for patient body weight and analysed as a categorical variable (& .75, 1.01–1.75 and & .01 mL/kg/h). The primary outcome was 28-day mortality. To deal with competing risk, we also compared different time epochs. We studied 347 patients {median age 64 [interquartile range (IQR) 53–71] years and Acute Physiology and Chronic Health Evaluation III score 73 [IQR 54–90]}. Compared with NUF rates & .01 mL/kg/h, NUF rates & .75 mL/kg/h were associated with greater mortality rates in each epoch: Days 0–5, adjusted hazard ratio (aHR) 1.27 [95% confidence interval (CI) 1.21–1.33] Days 6–10, aHR 1.62 (95% CI 1.55–1.68) Days 11–15, aHR 1.87 (95% CI 1.79–1.94) Days 16–26, aHR 1.92 (95% CI 1.84–2.01) and Days 27–28, aHR 4.18 (95% CI 3.98–4.40). For every 0.5 mL/kg/h NUF rate increase, mortality similarly increased during these epochs. Compared with early NUF rates & .01 mL/kg/h, NUF rates & .75 mL/kg/h are associated with increased mortality. These observations provide the rationale for clinical trials to confirm or refute these findings.
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000371748
Abstract: b i Background: /i /b Despite standardized definitions of acute kidney injury (AKI), there is wide variation in the reported rates of AKI and hospital mortality for patients with AKI. Variation could be due to actual differences in disease incidence, clinical course, or a function of data ascertainment and application of diagnostic criteria. Using standard criteria may help determine and compare the risk and outcomes of AKI across centers. b i Methods: /i /b In this cohort study of critically ill patients admitted to the intensive care units at six hospitals in four countries, we used KDIGO criteria to define AKI. The main outcomes were the occurrence of AKI and hospital mortality. b i Results: /i /b Of the 15,132 critically ill patients, 32% developed AKI based on serum creatinine criteria. After adjusting for differences in age, sex, and severity of illness, the odds ratio for AKI continued to vary across centers (odds ratio (OR), 2.57-6.04, p 0.001). The overall, crude hospital mortality of patients with AKI was 27%, which also varied across centers after adjusting for KDIGO stage, differences in age, sex, and severity of illness (OR, 1.13-2.20, p 0.001). The severity of AKI was associated with incremental mortality risk across centers. b i Conclusions: /i /b In this study, the absolute and severity-adjusted rates of AKI and hospital mortality rates for AKI varied across centers. Future studies should examine whether variation in the risk of AKI among centers is due to differences in clinical practice or process of care or residual confounding due to unmeasured factors.
Publisher: Springer Science and Business Media LLC
Date: 06-04-2021
Publisher: Springer Science and Business Media LLC
Date: 20-08-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2010
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 20-08-2013
Publisher: Massachusetts Medical Society
Date: 12-03-2015
DOI: 10.1056/NEJMC1500327
Publisher: Springer Science and Business Media LLC
Date: 08-05-2015
DOI: 10.1007/S00134-015-3822-1
Abstract: To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601] pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57% P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0% P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41] P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65) P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71% P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07) P = 0.33]. EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.
Publisher: Elsevier BV
Date: 08-2012
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 07-2013
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.JCRC.2016.05.017
Abstract: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Despite wide variability between in iduals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1093/BJA/AEU300
Publisher: American Chemical Society (ACS)
Date: 17-03-2021
Publisher: Elsevier BV
Date: 05-2016
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1093/BJA/AEU140
Publisher: Springer Science and Business Media LLC
Date: 2004
DOI: 10.1186/CC2872
Publisher: Springer Science and Business Media LLC
Date: 27-02-2017
Abstract: Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.
Publisher: Springer Science and Business Media LLC
Date: 2010
DOI: 10.1186/CC8933
Publisher: Elsevier BV
Date: 2015
DOI: 10.1093/BJA/AEU406
Publisher: American Chemical Society (ACS)
Date: 16-11-2018
Abstract: Graphene oxide (GO), an oxidized form of graphene, has potential applications in biomedical research. However, how GO interacts with biological systems, including the innate immune system, is poorly understood. Here, we elucidate the effects of GO sheets on macrophages, identifying distinctive effects of GO on the inflammatory phenotype. Small, thin (s)-GO dose-dependently inhibited release of interleukin (IL)-1β and IL-6 but not tumor necrosis factor α. NLRP3 inflammasome and caspase-1 activation was not affected. The effect of s-GO was pretranslational, as s-GO blocked Toll-like receptor 4-dependent expression of Il1b and Il6 but not Nlrp3 or Tnf mRNA transcripts. s-GO was internalized by immortalized bone-marrow-derived macrophages, suggesting a potential intracellular action. Uptake of polystyrene beads with similar lateral dimensions and surface charge did not phenocopy the effects of s-GO, suggesting that s-GO-mediated inhibition of interleukin expression was not simply due to particle phagocytosis. RNA-Seq analysis established that s-GO had profound effects on the immunometabolism of the cells, leading to activation of the transcription factor nuclear factor erythroid 2-related factor 2, which inhibited expression of cytokines such as IL-1β and IL-6. Thus, we have identified immunometabolic effects of GO that reveal another dimension to its effects on cells. These findings suggest that s-GO may be used as a valuable tool to generate further insights into inflammatory mechanisms and indicate its potential applications in biomedicine.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2021
DOI: 10.1038/S41581-021-00410-W
Abstract: Over the past decade, new insights into epidemiology, pathophysiology and biomarkers have modified our understanding of acute kidney dysfunction and damage, and their association with subsequent chronic kidney disease. The concept of acute kidney injury (AKI), which has relied on established but nonetheless flawed biomarkers of solute clearance (serum creatinine levels and urinary output), has been challenged by the identification of novel biomarkers of tubular stress and/or damage. The expression of some of these novel biomarkers precedes changes in conventional biomarkers or can increase their predictive power, and might therefore enhance the clinical accuracy of the definition of AKI. In addition, the need to consider AKI recurrence, duration and progression to chronic kidney disease within the clinical and epidemiological framework of AKI led to the emergence of the concept of acute kidney disease. New definitions of acute syndromes of kidney impairment and injury are needed.
Publisher: Oxford University Press (OUP)
Date: 25-01-2010
DOI: 10.1093/NDT/GFP766
Abstract: A pre-morbid 'baseline' creatinine is required in order to diagnose and stage acute kidney injury (AKI) using the RIFLE classification. Estimation of baseline creatinine by solving the Modification of Diet in Renal Disease (MDRD) equation assuming a glomerular filtration rate of 75 ml/min/1.73 m(2) has been widely used but never validated. We analysed four cohorts of intensive care unit (ICU) patients from three centres (two from Pittsburgh and one from Mayo and Austin). Three cohorts consisted of preselected patients without AKI (Pittsburgh 1 n = 1048, Mayo n = 737, Austin n = 333), and measured creatinine values in these cohorts were taken to represent baseline creatinine values. The last cohort (Pittsburgh 2 n = 468) consisted of unselected ICU patients with baseline creatinine values recorded within 1 year before ICU admission. Using the Pittsburgh 1 cohort, we derived an equation using the same anthropometric variables as the MDRD equation: baseline creatinine = 0.74 - 0.2 (if female) + 0.08 (if black) + 0.003 × age (in years). We then compared measured creatinine in the Mayo and Austin cohorts and recorded creatinine in the Pittsburgh 2 cohort to the estimated creatinine from: (i) the MDRD equation (ii) our new equation (iii) a gender-fixed creatinine of 0.8 mg/dl for females and 1.0 mg/dl for males. Using any of the three methods, the median absolute error of the estimates was of the order of 0.1-0.2 mg/dl, and overall accuracy was similar. When the definition of AKI was limited to the severity grades of Injury and Failure, all three methods were able to generate 78-90% reliable results for preselected normal range cohorts, and 63-70% for the unselected cohort of ICU patients. Estimates of incidence of AKI in the critically ill using RIFLE classification can be affected by the bias and limited accuracy of methods to estimate baseline creatinine. Whenever possible, recorded creatinine values should be used as a reference of baseline. The use of the MDRD equation to estimate baseline creatinine when it is unknown may over- or underestimate some mild (Risk) AKI cases but is unlikely to misclassify patients in Injury and Failure.
Publisher: Springer Science and Business Media LLC
Date: 16-03-2010
Abstract: The prevalence of anemia in the intensive care unit is well-described. Less is known, however, of the prevalence of anemia in hospitalized patients with lesser illness severity or without organ dysfunction. Community-acquired pneumonia (CAP) is one of the most frequent reasons for hospitalization in the United States (US), affecting both healthy patients and those with comorbid illness, and is typically not associated with acute blood loss. Our objective was to examine the development and progression of anemia and its association with 90d mortality in 1893 subjects with CAP presenting to the emergency departments of 28 US academic and community hospitals. We utilized hemoglobin values obtained for clinical purposes, classifying subjects into categories consisting of no anemia (hemoglobin g/dL), at least borderline (≤ 13 g/dL), at least mild (≤ 12 g/dL), at least moderate (≤ 10 g/dL), and severe (≤ 8 g/dL) anemia. We stratified our results by gender, comorbidity, ICU admission, and development of severe sepsis. We used multivariable logistic regression to determine factors independently associated with the development of moderate to severe anemia and to examine the relationship between anemia and 90d mortality. A total of 8240 daily hemoglobin values were measured in 1893 subjects. Mean (SD) number of hemoglobin values per patient was 4.4 (4.0). One in three subjects (33.9%) had at least mild anemia at presentation, 3 in 5 (62.1%) were anemic at some point during their hospital stay, and 1 in 2 (54.5%) survivors were discharged from the hospital anemic. Anemia increased with illness severity and was more common in those with comorbid illnesses, female gender, and poor outcomes. Yet, even among men and in those with no comorbidity or only mild illness, anemia during hospitalization was common (~55% of subjects). When anemia was moderate to severe (≤ 10 g/dL), its development was independently associated with increased 90d mortality, even among hospital survivors. Anemia was common in hospitalized CAP and independently associated with 90d mortality when hemoglobin values were 10 g/dL or less. Whether prevention or treatment of CAP-associated anemia would improve clinical outcomes remains to be seen.
Publisher: Springer Science and Business Media LLC
Date: 31-03-2017
DOI: 10.1007/S00134-017-4755-7
Abstract: Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 17-02-2017
Publisher: Springer Science and Business Media LLC
Date: 08-09-2009
Publisher: Springer Science and Business Media LLC
Date: 2012
DOI: 10.1186/CC11188
Publisher: S. Karger AG
Date: 21-07-2021
DOI: 10.1159/000517281
Abstract: b i Introduction: /i /b Higher net ultrafiltration (UF sub NET /sub ) rates are associated with mortality among critically ill patients with acute kidney injury (AKI) and treated with continuous renal replacement therapy (CRRT). b i Objective: /i /b The aim of the study was to discover whether UF sub NET /sub rates are associated with renal recovery and independence from renal replacement therapy (RRT). b i Methods: /i /b Retrospective cohort study using data from the Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy trial that enrolled 1,433 critically ill patients with AKI and treated with CRRT between December 2005 and November 2008 across 35 intensive care units in Australia and New Zealand. We examined the association between UF sub NET /sub rate and time to independence from RRT by day 90 using competing risk regression after accounting for mortality. The UF sub NET /sub rate was defined as the volume of fluid removed per hour adjusted for patient body weight. b i Results and Conclusions: /i /b Median age was 67.3 (interquartile range [IQR], 57–76.3) years, 64.4% were male, median Acute Physiology and Chronic Health Evaluation-III score was 100 (IQR, 84–118), and 634 (44.2%) died by day 90. Kidney recovery occurred in 755 patients (52.7%). Using tertiles of UF sub NET /sub rates, 3 groups were defined: high, & #x3e .75 middle, 1.01–1.75 and low, & #x3c .01 mL/kg/h. Proportion of patients alive and independent of RRT among the groups were 47.8 versus 57.2 versus 53.0% i /i = 0.01. Using competing risk regression, higher UF sub NET /sub rate tertile compared with middle (cause-specific hazard ratio [csHR], 0.79, 95% CI, 0.66–0.95 subdistribution hazard ratio [sHR], 0.80, 95% CI, 0.67–0.97) and lower (csHR, 0.69, 95% CI, 0.56–0.85 sHR, 0.78, 95% CI 0.64–0.95) tertiles were associated with a longer time to independence from RRT. Every 1.0 mL/kg/h increase in rate was associated with a lower probability of kidney recovery (csHR, 0.81, 95% CI, 0.74–0.89 and sHR, 0.87, 95% CI, 0.80–0.95). Using the joint model, longitudinal increases in UF sub NET /sub rates were also associated with a lower renal recovery (β = −0.29, i /i & #x3c 0.001). UF sub NET /sub rates & #x3e .75 mL/kg/h compared with rates 1.01–1.75 and & #x3c .01 mL/kg/h were associated with a longer duration of dependence on RRT. Randomized clinical trials are required to confirm this UF sub NET /sub rate-outcome relationship.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2021
Publisher: Elsevier BV
Date: 12-2012
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1093/BJA/AEU298
Abstract: Despite many clinical trials and investigative efforts to determine appropriate therapeutic intervention(s) for shock, this topic remains controversial. The use of i.v. fluid has represented the cornerstone for the treatment of hypoperfusion for two centuries. As a part of International Acute Dialysis Quality Initiative XII Fluids Workgroup meeting, we sought to incorporate recent advances in our understanding of vascular biology into a more comprehensive yet accessible approach to the patient with hypoperfusion. In this workgroup, we attempted to develop a framework that incorporates key aspects of the vasculature into a diagnostic approach. The four main components of our proposal involve the assessment of the blood flow (BF), vascular content (vC), the vascular barrier (vB), and vascular tone (vT). Any significant perturbation in any of these domains can lead to hypoperfusion at both the macro- and micro-circulatory level. We have termed the BF, vC, vB, and vT diagnostic approach the vascular component (VC) approach. The VC approach to hypoperfusion has potential advantages to the current diagnostic system. This approach also has the distinct advantage that it can be used to assess the systemic, regional, and micro-vasculature, thereby harmonizing the approach to clinical vascular diagnostics across these levels. The VC approach will need to be tested prospectively to determine if this system can in fact improve outcomes in patients who suffer from hypoperfusion.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1093/BJA/AEU297
Abstract: The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to all aspects of fluid therapy, including the management of fluid overload (FO). The aim of the working subgroup 'Mechanical fluid removal' was to review the indications, prescription, and management of mechanical fluid removal within the broad context of fluid management of critically ill patients. The working group developed a list of preliminary questions and objectives and performed a modified Delphi analysis of the existing literature. Relevant studies were identified through a literature search using the MEDLINE database and bibliographies of relevant research and review articles. After review of the existing literature, the group agreed the following consensus statements: (i) in critically ill patients with FO and with failure of or inadequate response to pharmacological therapy, mechanical fluid removal should be considered as a therapy to optimize fluid balance. (ii) When using mechanical fluid removal or management, targets for rate of fluid removal and net fluid removal should be based upon the overall fluid balance of the patient and also physiological variables, in idualized, and reassessed frequently. (iii) More research on the role and practice of mechanical fluid removal in critically ill patients not meeting fluid balance goals (including in children) is necessary. Mechanical fluid removal should be considered as a therapy for FO, but more research is necessary to determine its exact role and clinical application.
Publisher: BMJ
Date: 15-02-2011
Abstract: To propose an improvement on the current classification of renal dysfunction in cirrhosis. Clinicians caring for patients with cirrhosis recognize that the development of renal dysfunction is associated with significant morbidity and mortality. While most cases of renal dysfunction in cirrhosis are functional in nature, developed as a result of changes in haemodynamics, cardiac function, and renal auto-regulation, there is an increasing number of patients with cirrhosis and structural changes in their kidney as a cause of renal dysfunction. Therefore, there is a need for a newer classification to include both functional and structural renal diseases. A working party consisting of specialists from multiple disciplines conducted literature search and developed summary statements, incorporating the renal dysfunction classification used in nephrology. These were discussed and revised to produce this proposal. Multi-disciplinary international meeting. None. Literature search using keywords of cirrhosis, renal dysfunction, acute kidney injury (AKI), chronic kidney injury (CKD), and hepatorenal syndrome. Acute kidney injury will include all causes of acute deterioration of renal function as indicated by an increase in serum creatinine of >50% from baseline, or a rise in serum creatinine of ≥ 26.4 µmol/L (≥ 0.3 mg/dL) in < 48 hours. Chronic renal disease will be defined as an estimated glomerular filtration rate (GFR) of < 60 ml/min calculated using the Modification of Diet in Renal Disease 6 (MDRD6) formula, recognising that the MDRD6 formula is not perfect for the cirrhotic patients and this may change as improved means of estimating GFR becomes available. Acute on chronic kidney disease will be defined as AKI superimposed on existing chronic renal disease using the above definitions for AKI and CKD. Accepting this new classification will allow studies into the epidemiology, incidence, prevalence, natural history and the development of new treatments for these subtypes of renal dysfunction in cirrhosis.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1093/BJA/AEU299
Abstract: Standard treatment practice for the hypotensive patient with poor tissue perfusion is rapid volume resuscitation in some scenarios, such as septic shock, this is performed with targeted goal-directed endpoints within 6 h of presentation. As a result, patients often develop significant positive fluid accumulation, which has been associated with poor outcomes above certain thresholds. The aim of the current paper is to provide guidance for active pharmacological fluid management in the patient with, or at risk for, clinically significant positive fluid balance from either resuscitation for hypovolaemic shock or acute decompensated heart failure. We develop rationale for pharmacological fluid management targets (prevention of worsening fluid accumulation, achievement of slow vs rapid net negative fluid balance) in the context of phases of critical illness provided in the earlier Acute Dialysis Quality Initiative 12 papers.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.JCRC.2007.12.017
Abstract: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients. Timing of RRT was stratified into "early" and "late" by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early ( 5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea 24.2 mmol/L odds ratio [OR], 0.92 95% confidence interval [CI], 0.73-1.15 P = .48) or covariate-adjusted mortality (OR, 1.25 95% CI, 0.91-1.70 P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine >309 micromol/L vs 71.4% for creatinine <or=309 micromol/L OR, 0.46 95% CI, 0.36-0.58 P < .0001) and covariate-adjusted mortality (OR, 0.51 95% CI, 0.37-0.69 P < .001). However, for timing relative to ICU admission, late RRT was associated with greater crude (72.8% vs 62.3% vs 59%, P < .001) and covariate-adjusted mortality (OR, 1.95 95% CI, 1.30-2.92 P = .001). Overall, late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence. Timing of RRT, a potentially modifiable factor, might exert an important influence on patient survival. However, this largely depended on its definition. Late RRT (days from admission) was associated with a longer duration of RRT, longer hospital stay, and higher dialysis dependence.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-01-2021
Location: United States of America
Location: Denmark
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for John Kellum.