Major Adverse Kidney Events Research Articles

Editor's Choice – Acute Kidney Injury (AKI) in Aortic Intervention: Findings From the Midlands Aortic Renal Injury (MARI) Cohort Study

The incidence of acute kidney injury (AKI) after open (OAR) or endovascular (EVAR) aortic repair is unknown. This research assessed the proportion of patients who develop AKI after aortic intervention using validated criteria, and explored AKI risk factors. This was a multicentre national prospective cohort study. Eleven centres recruited patients undergoing EVAR or OAR (September 2017-December 2018). Serum creatinine (SCr) and urine outputs were measured over a minimum of 48h or throughout the index inpatient stay to define post-operative AKI using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Renal decline at 30 days was calculated using estimated glomerular filtration rate (eGFR) and the Major Adverse Kidney Events (MAKE) 30 day composite endpoint (consisting of: death, new dialysis, > 25% eGFR decline). 300 patients (mean age: 71 years, standard deviation [SD] 4 years; 9% females) were included, who underwent: infrarenal endovascular aneurysm repair (EVAR) 139 patients, fenestrated EVAR (fEVAR) 30, branched EVAR (bEVAR) seven, infrarenal open aneurysm repair (OAR) 98, juxtarenal OAR 26. Overall, 24% of patients developed stage 1 AKI (defined at 48h as per KDIGO), 2.7% stage 2 AKI and 1% needed renal replacement therapy before discharge. AKI proportions per intervention were: infrarenal EVAR 18%; fEVAR 27%; bEVAR 71%; infrarenal OAR 41%; juxtarenal OAR 63%. Older age (odds ratio [OR] 1.44 for EVAR, 1.58 for OAR), lower baseline eGFR (OR 0.88 EVAR, 0.74 OAR), and ischaemic heart disease (OR 4.42 EVAR, 5.80 OAR) were the main predictors of AKI for infrarenal EVAR and OAR. Overall, 24% developed the MAKE30 endpoint. All patients who died (0.6%) or developed a major cardiac event (5.6%) at one year had developed AKI. AKI and short term renal decline after aortic intervention are common. Age, renal function, and cardiovascular disease are the main risk factors. Research should now focus on AKI prevention in this high risk group.

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study

BackgroundThe use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored.MethodsWe conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models.ResultsAmong 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively.ConclusionHydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation.Trial registrationClinicalTrials.gov, NCT03558646

Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study.

BackgroundThe ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events.MethodsThis pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement.ResultsNGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.07 [1.01–1.14]), Interleukin-6 (1.51 [1.01–2.26]), midkine (1.01 [1.00–1.02]), 1-hepcidin-25 (1.08 [1.00–1.17]), and NGAL/hepcidin-ratio (2.91 [1.30–6.49]) were independent predictors of MAKE and AKI (1.38 [1.03–1.85], 1.08 [1.01–1.15], 1.01 [1.00–1.02], 1.09 [1.01–1.18], and 3.45 [1.54–7.72]). Category-free net reclassification improvement identified interleukin-6 as a model-improving biomarker for MAKE and NGAL for AKI. However, only NGAL/hepcidin-25 improved model performance for event- and event-free patients for MAKE and AKI.ConclusionsNGAL and interleukin-6 measured immediately post cardiac surgery may complement the Cleveland Score. The combination of biomarkers with hepcidin-25 may further improve diagnostic discrimination.

Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI: A Substudy of the PRESERVE Trial

The PRESERVE trial used a 2 × 2 factorial design to compare intravenous saline solution with intravenous sodium bicarbonate solution and oral N-acetylcysteine with placebo for the prevention of 90-day major adverse kidney events and death (MAKE-D) and contrast-associated acute kidney injury (CA-AKI) among patients with chronic kidney disease undergoing angiography. In this ancillary study, we evaluated the predictive capacities of preangiography injury and repair proteins in urine and plasma for MAKE-D, CA-AKI, and their impact on trial design. Longitudinal analysis. A subset of participants from the PRESERVE trial. Injury (KIM-1, NGAL, and IL-18) and repair (MCP-1, UMOD, and YKL-40) proteins in urine and plasma 1 to 2 hours preangiography. MAKE-D and CA-AKI. We analyzed the associations of preangiography biomarkers with MAKE-D and with CA-AKI. We evaluated whether thebiomarker levels could enrich the MAKE-D event rate and improve future clinical trial efficiency through an online biomarker prognostic enrichment tool available at prognosticenrichment.com. We measured plasma biomarkers in 916 participants and urine biomarkers in 797 participants. After adjusting for urinary albumin-creatinine ratio and baseline estimated glomerular filtration rate, preangiography levels of 4 plasma (KIM-1, NGAL, UMOD, and YKL-40) and 3 urine (NGAL, IL-18, and YKL-40) biomarkers were associated with MAKE-D. Only plasma KIM-1 level was significantly associated with CA-AKI after adjustment. Biomarker levels provided modest discriminatory capacity for MAKE-D. Screening patients using the 50th percentile of preangiography plasma KIM-1 or YKL-40 levels would have reduced the required sample size by 30% (∼2,000 participants). Evaluation of prognostic enrichment does not account for changing trial costs, time needed to screen patients, or loss to follow-up. Most participants were male, limiting the generalizability of our findings. Preangiography levels of injury and repair biomarkers modestly predict the development of MAKE-D and can be used to improve the efficiency of future CA-AKI trials.

Fluid Overload Associates With Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

We examined the association between fluid overload and major adverse kidney events in critically ill patients requiring continuous renal replacement therapy for acute kidney injury. Retrospective cohort study. ICU in a tertiary medical center. Four-hundred eighty-one critically ill adults requiring continuous renal replacement therapy for acute kidney injury. None. Fluid overload was assessed as fluid balance from admission to continuous renal replacement therapy initiation, adjusted for body weight. Major adverse kidney events were defined as a composite of mortality, renal replacement therapy-dependence or inability to recover 50% of baseline estimated glomerular filtration rate (if not on renal replacement therapy) evaluated up to 90 days after discharge. Patients with fluid overload less than or equal to 10% were less likely to experience major adverse kidney events than those with fluid overload greater than 10% (71.6% vs 79.4%; p = 0.047). Multivariable logistic regression showed that fluid overload greater than 10% was associated with a 58% increased odds of major adverse kidney events (p = 0.046), even after adjusting for timing of continuous renal replacement therapy initiation. There was also a 2.7% increased odds of major adverse kidney events for every 1 day increase from ICU admission to continuous renal replacement therapy initiation (p = 0.024). Fluid overload greater than 10% was also found to be independently associated with an 82% increased odds of hospital mortality (p = 0.004) and 2.5 fewer ventilator-free days (p = 0.044), compared with fluid overload less than or equal to 10%. In critically ill patients with acute kidney injury requiring continuous renal replacement therapy, greater than 10% fluid overload was associated with higher risk of 90-day major adverse kidney events, including mortality and decreased renal recovery. Increased time between ICU admission and continuous renal replacement therapy initiation was also associated with decreased renal recovery. Fluid overload represents a potentially modifiable risk factor, independent of timing of continuous renal replacement therapy initiation, that should be further examined in interventional studies.

Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis.

Background: The optimal resuscitative fluid remains controversial. Objective: To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; I2 = 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2 = 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; I2 = 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2 = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2 = 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; I2 = 42%). Conclusion and Relevance: Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.

Hypotension within one-hour from starting CRRT is associated with in-hospital mortality

PurposeTo investigate early hemodynamic instability and its implications on adverse outcomes in patients who require continuous renal replacement therapy (CRRT). Materials and methodsA retrospective study of patients admitted to the intensive care unit (ICU) and underwent CRRT at Mayo Clinic, Rochester, Minnesota between December 2006 through November 2015. ResultsMultivariate logistic regression was performed to identify predictors of in-hospital mortality and major adverse kidney events (MAKE) at 90 days. Hypotension was defined as any of the following criteria occurring during the first hour of CRRT initiation: mean arterial pressure < 60 mmHg, systolic blood pressure (SBP) <90 mmHg or a decline in SBP >40 mmHg from baseline, a positive fluid balance >500 mL or increased vasopressor requirement. The analysis included 1743 patients, 1398 with acute kidney injury (AKI). In-hospital mortality occurred in 884 patients (51%). Early hypotension occurred in 1124 patients (64.6%) and remained independently associated with in-hospital mortality (OR 1.56, 95% CI: 1.25–1.9). ConclusionHypotension occurs frequently in patients receiving CRRT despite having a reputation as the dialysis modality with better hemodynamic tolerance. It is an independent predictor for worse outcomes. Further studies are required to understand this phenomenon.

SUN-164 ASSOCIATION BETWEEN INTRAVENOUS CONTRAST MEDIA AND NON-RECOVERY FROM DIALYSIS-REQUIRING SEPTIC ACUTE KIDNEY INJURY IN INTENSIVE CARE UNIT PATIENTS: A NATIONWIDE OBSERVATIONAL STUDY

Although the concern of the effect of iodinated contrast media on acute kidney injury (AKI) affects physician’s decision on the usage of contrast media with computed tomography (CT), recent reports have questioned the causal relationship between administration of intravenous contrast media and the subsequent AKI, and its causal relationship is still controversial. However, there are no previous reports about whether iodinated-contrast media increase non-renal recovery in critically ill patients who require renal replacement therapy (RRT) early after admission. In this retrospective observational study using the Japanese Diagnosis Procedure Combination inpatient database during a period between July 1, 2011 and March 31, 2017, we identified patients with septic AKI who required continuous renal replacement therapy (CRRT) within 1 day after admission. Patients were divided into those who received computed tomography with intravenous contrast media and those without contrast media. We performed propensity score matching to control potential confounders and analyzed associations between exposure to intravenous contrast media and outcomes, including major adverse kidney events (MAKE) which was defined as death and RRT-dependence at discharge, and duration of RRT. A total of 9,055 patients (3293 with contrast media and 5762 without contrast media) were eligible. Propensity score matching analyses showed MAKE at discharge was not statistically different between the groups with and without contract media (49.6% vs 50.7%, p=0.441). RRT duration was median 5 days and also not significantly different between the groups. Use of intravenous contrast media was not associated with increase in MAKE or RRT duration in patients with septic dialysis-requiring AKI.

Choice of Intravenous Crystalloid Fluid and Mortality in Critically Ill Adult Patients.

Intravenous balanced crystalloid fluid therapy may improve mortality and other outcomes in critically ill adult patients, but data are conflicting. We conducted a meta-analysis and literature review to evaluate the impact of intravenous balanced crystalloid, as compared with normal saline, fluid therapy on outcomes in critically ill adult patients. We searched PubMed, Scopus, MEDLINE, and the Cochrane Register of Clinical Trials for relevant studies. Randomized controlled trials comparing the effects of balanced intravenous crystalloids with normal saline on intensive care unit (ICU) or hospital mortality were included. Pooled risk ratios (RRs) were calculated using a fixed effects model. Heterogeneity was calculated using the I2 statistic. The risk of bias was assessed using the Cochrane tool. Seven randomized controlled trials with 20,171 patients (10,179 participants received balanced crystalloids and 9992 participants received normal saline) were included. For hospital mortality, the pooled RR (95% confidence interval [CI]) was 0.92 (0.85-1.00). For ICU mortality, the pooled RR (95% CI) was 0.91 (0.82-1.00). For major adverse kidney events at 30 days, pooled RR (95% CI) was 0.95 (0.88-1.01). For stage ≥2 acute kidney injury, the pooled RR (95% CI) was 0.94 (0.86-1.02). For receipt of new renal replacement therapy, the pooled RR (95% CI) was 0.91 (0.77-1.07). None of these findings reached statistical significance. Intravenous balanced crystalloid use, compared with normal saline, does not result in a statistically significant reduction in hospital or ICU mortality, major adverse kidney events at 30 days, stage ≥2 acute kidney injury, or receipt of new renal replacement therapy in critically ill adult patients.

Protocol of a randomised controlled trial in cardiac surgical patients with endothelial dysfunction aimed to prevent postoperative acute kidney injury by administering nitric oxide gas

IntroductionPostoperative acute kidney injury (AKI) is a common complication in cardiac surgery. Levels of intravascular haemolysis are strongly associated with postoperative AKI and with prolonged (>90 min) use of cardiopulmonary...

Urine Klotho Is Lower in Critically Ill Patients With Versus Without Acute Kidney Injury and Associates With Major Adverse Kidney Events.

Klotho and Fibroblast Growth Factor (FGF)-23 were recently postulated as candidate biomarkers and/or therapeutic targets in acute kidney injury (AKI). We examined whether urine Klotho and serum intact FGF23 levels were differentially and independently associated with major adverse kidney events (MAKE) in critically ill patients with and without AKI. Single-center, prospective, case-control study. ICU in a tertiary medical center. 54 AKI patients and 52 controls without AKI admitted to the ICU. None. AKI was defined by KDIGO criteria and included only AKI stage ≥2. Controls were matched by age, gender, and baseline eGFR. Paired serum and urine samples were obtained 24-48h after AKI diagnosis (cases) or ICU admission (controls). The primary outcome was 90-day MAKE, which was the composite of all-cause death, dependence on renal replacement therapy or a 50% or higher decrease in eGFR from baseline. Forty-four (41.5%) patients developed MAKE-90. Patients who developed MAKE-90 had more comorbidity, higher acuity of illness scores and more prevalent AKI. Levels of urine Klotho adjusted by creatinine (Cr) were lower and serum intact FGF23 levels were higher in AKI patients vs. ICU controls. In adjusted models, the highest vs. lowest tertile of urine Klotho/Cr was independently associated with an overall 95% lower risk of MAKE-90 (81% lower risk in patients with AKI). The highest vs. lowest tertile of serum intact FGF23 was associated with >300% higher risk of MAKE-90. Urine Klotho/Cr levels were significantly lower and serum intact FGF23 levels significantly higher in critically ill patients with AKI vs. matched-controls without AKI. When measured in the first 48h of ICU admission or AKI diagnosis, urine Klotho/Cr independently associated with major adverse kidney events, particularly in patients with AKI. These results show promise for testing these biomarkers -individually or in combination- as part of novel risk-prediction models of renal outcomes in the ICU.

Major Adverse Kidney Events in Pediatric Sepsis.

Major adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis. We conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality. Of 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%; P<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697; P<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m2 between 3 months and 1 year after discharge (19% versus 4%; P=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions. In children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.

Long-term outcomes after extracorporeal membrane oxygenation in patients with dialysis-requiring acute kidney injury: A cohort study.

BackgroundAcute kidney injury (AKI) is a common complication of extracorporeal membrane oxygenation (ECMO) treatment. The aim of this study was to elucidate the long-term outcomes of adult patients with AKI who receive ECMO.Materials and methodsThe study analyzed encrypted datasets from Taiwan’s National Health Insurance Research Database. The data of 3251 patients who received first-time ECMO treatment between January 1, 2003, and December 31, 2013, were analyzed. Characteristics and outcomes were compared between patients who required dialysis for AKI (D-AKI) and those who did not in order to evaluate the impact of D-AKI on long-term mortality and major adverse kidney events.ResultsOf the 3251 patients, 54.1% had D-AKI. Compared with the patients without D-AKI, those with D-AKI had higher rates of all-cause mortality (52.3% vs. 33.3%; adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 1.53–2.17), chronic kidney disease (13.7% vs. 8.1%; adjusted subdistribution HR [aSHR] 1.66, 95% CI 1.16–2.38), and end-stage renal disease (5.2% vs. 0.5%; aSHR 14.28, 95% CI 4.67–43.62). The long-term mortality of patients who survived more than 90 days after discharge was 22.0% (153/695), 32.3% (91/282), and 50.0% (10/20) in the patients without D-AKI, with recovery D-AKI, and with nonrecovery D-AKI who required long-term dialysis, respectively, demonstrating a significant trend (Pfor trend <0.001).ConclusionAKI is associated with an increased risk of long-term mortality and major adverse kidney events in adult patients who receive ECMO.

Regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH) trial: study protocol for a multicentre, randomised controlled trial

IntroductionAcute kidney injury (AKI) is a well-recognised complication of critical illness which is of crucial importance for morbidity, mortality and health resource utilisation. Renal replacement therapy (RRT) inevitably entails an...

Editorial introductions

Current Opinion in Critical Care was launched in 1995. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of critical care is divided into 13 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the journal's Section Editors for this issue. SECTION EDITORS Thomas RimmeléThomas RimmeléProf. Thomas Rimmelé is the Chairman of the Department of Anaesthesiology and Intensive Care Medicine at Edouard Herriot Hospital, Lyon, France, and Chairman of the Department of Organ Harvest Coordination for the Hospices Civils de Lyon, France. He gained his medical degree in 2004, specialising in anaesthesiology and intensive care, from the Claude Bernard University, Lyon, France, and subsequently completed a PhD on extracorporeal blood purification therapies in sepsis. In addition to blood purification for sepsis, Prof. Rimmelé's academic interests include acute kidney injury, renal replacement therapy in the intensive care unit, and simulation in healthcare as he is also the co-director of the simulation center at Lyon University, France. Prof. Rimmelé is the author or co-author of more than 150 peer-reviewed articles or book chapters and regularly delivers lectures at international meetings. Wesley H. SelfWesley H. SelfDr Wesley H. Self, MD, MPH, is the Vice Chair for Research in the Department of Emergency Medicine at Vanderbilt University Medical Center in Nashville, Tennessee, USA. He is an emergency physician and clinical researcher focused on the intersection of emergency and critical care medicine. He has authored over 100 peer-reviewed publications and widely lectured and presented research findings on the early management of pneumonia, sepsis, and related emergencies. Dr Self was the principal investigator for the Saline Against Lactated Ringer's or Plasmalyte in the Emergency Department (SALT-ED) trial (N Engl J Med 2018), which demonstrated a lower incidence of major adverse kidney events following IV fluid resuscitation with balanced crystalloids compared with saline. He was also a lead investigator in the Etiology of Pneumonia in the Community (EPIC) study (N Engl J Med 2015), which demonstrated a high disease burden from respiratory viruses among patients hospitalized with community-acquired pneumonia in the United States. Dr Self serves as the co-principal investigator of the Vanderbilt Clinical Center in the Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network (www.petalnet.org) funded by the National Heart, Lung and Blood Institute (NHLBI). His current work focuses on embedding pragmatic comparative effectiveness trials into ongoing clinical care to learn how to improve early resuscitation. Dr Self completed medical school at the University of Virginia, USA, residency training in emergency medicine at Northwestern University, USA, and a clinical research fellowship at Vanderbilt University, USA. He is currently an Associate Professor of Emergency Medicine at Vanderbilt University Medical Center, where he leads the Division of Emergency Medicine Research. Karim AsehnouneKarim AsehnouneProf. Karim Asehnoune got his degree as an MD in 1999 at University René Descartes Paris, France. After completing his PhD in immunology in 2001, he spent one year in the lab of Prof. Edward Abraham in the University of Colorado, Denver, USA (2002). He was appointed Professor of Anaesthesiology and Critical Care Medicine in the University of Nantes, France, in 2009. Prof. Asehnoune is the head of the Anaesthesiology department of Hospital Hotel-Dieu, and the director of the 30-bed surgical Intensive Care Unit at the University hospital of Nantes, France. He is currently a member of the scientific committee of the French Society of Anaesthesiology and Critical Care Medicine, and the director of a French network of ICUs (www.ATLANREA.org). Professor Asehnoune was involved as the coordinator of several multi-centre trials, and he was the primary investigator of 2 multicentre double blind randomised studies evaluating corticosteroids in severe trauma patients. He is the director of a lab dedicated to the study of host-pathogen interactions (http://www.ea3826.univ-nantes.fr/). He has published more than 180 peer-reviewed articles.

Impact of an Acinetobacter baumannii outbreak on kidney events in a burn unit: A targeted machine learning analysis

Multidrug-resistant (MDR) bacteria outbreaks represent a major threat in intensive care units. Patients may then be exposed to drug-related direct toxicity during such outbreaks. The objective of this study was to explore the impact of an outbreak of imipenem-resistant Acinetobacter baumannii (IR-AB) on renal outcomes. We performed a before-and-after observational study in a French burn intensive care unit during an IR-AB outbreak: a 13-month period before (period A, October 2013-October 2014) and a 13-month period after outbreak control (period B, December 2014-December 2015). A total of 409 patients were included, 195 during period A and 214 during period B. The main endpoint was major adverse kidney events at day 90 (MAKE 90). Secondary endpoints were acute kidney injury (AKI) and persistent renal dysfunction. Incidence of MAKE 90 was 15.9% during period A versus 11.2% during period B (P = .166) and AKI 28.2% versus 18.7% (P = .023). The use of colistin was associated with renal outcomes in univariate analysis. After adjustment of potential confounding factors using a targeted Machine Learning Analysis (ie, IR-AB-related infection, septic shock, severity scores, other nephrotoxics, chronic kidney disease, serum creatinine at admission, Staphylococcus aureus), colistin remained associated with the risk of MAKE and AKI (relative risk = 2.909, 95% confidence interval [CI] [1.364, 6.204], P = .006for MAKE 90, and relative risk = 2.14, 95% CI [1.52, 3.02], P<.0001 for AKI). The episode of IR-AB outbreak was associated with an increased risk of kidney events, which appears to be driven by the use of colistin.

Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery.

No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery. To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively. The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62-0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41-0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36-0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18-0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17-0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20-1.10; P = 0.041). In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).

The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients

BackgroundRecent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells.MethodsWe conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28.ResultsFifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups.ConclusionPMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression.Trial registrationClinicalTrials.gov, NCT02413541. Registered on 3 March 2015.

Prediction of major adverse kidney events in critically ill burn patients

ObjectiveWe aimed at assessing the predictive value of plasmatic Neutrophil Gelatinase Associated Lipocalin (pNGAL) at admission and severity scores to predict major adverse kidney events (MAKE, defined as death and/or need for renal replacement therapy (RRT) and/or non-renal recovery at day 90) in critically ill burn patients. Material and methodsSingle-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients (total burned body surface >20%) from January 2012 until January 2015 with a pNGAL dosage at admission. Reclassification of patients was assessed by Integrated Discrimination Improvement (IDI). Measurements and results87 patients were included. Mean age was 47.7 (IQ 25–75: 33.4–65.2) years; total burn body surface area was 40 (IQ 25–75: 30–55) % and ICU mortality 36%. 39 (44.8%) patients presented a MAKE, 32 (88.9%) patients died at day 90. pNGAL was higher in the MAKE group (423 [IQ 25–75: 327–518]pg/mL vs 184 [IQ 25–75: 147–220]pg/mL, p<0.001). In multivariate analysis, pNGAL and abbreviated burn severity index (ABSI) remained associated with MAKE (OR 1.005 [CI 95% 1.0005–1.009], p=0.03 and OR 1.682 [CI95%1.038–2.726], p=0.035 respectively). Adding pNGAL to abbreviated burn severity index, simplified organ failure assessment and the simplified acute physiology score 2 did outperform clinical scores for the prediction of MAKE and AKI and for most severe forms of AKI and allowed a statistically significant reclassification of patients compared to ABSI for MAKE, RRT, AKI at Day 7 and AKI during hospitalization with a number of patients needed to screen to detect one extra episode of MAKE was 44, 13 for severe AKI and 15 for AKI. ConclusionspNGAL at admission is associated with the risk of MAKE in this population, and outperform severity scores when associated. Interventional studies are now needed to assess if impact of biomarkers-guided strategies would improve outcome.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: renal endpoints

BackgroundRenal injury is a common perioperative complication. The adoption of renal endpoints, standardised and valid for use in perioperative clinical trials, would enhance the quality of perioperative clinical research. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive standardised endpoints for use in perioperative clinical trials. MethodsA systematic review was conducted to identify renal endpoints currently reported in perioperative clinical trials. In parallel, an initial list of candidate endpoints was developed based on renal theme group expertise. A multi-round Delphi consensus process was used to refine this list and produce a suite of recommended perioperative renal outcome measures. ResultsBased on our systematic review, 63 studies were included for analysis. Marked heterogeneity and imprecision of endpoint definitions were observed. Our initial list of candidate endpoints included 10 endpoints for consideration. The response rates for Delphi rounds 1, 2, and 3 were 89% (n=16), 90% (n=75), and 100% (n=6), respectively. A final list of four renal endpoints was identified: acute kidney injury defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consensus criteria, acute kidney disease defined by ≥30% decline in estimated glomerular filtration rate from baseline at 30 days after operation in patients meeting the acute-kidney-injury criteria within 7 days of surgery, the composite of death or renal replacement therapy, and the Major Adverse Kidney Events (MAKE) composite. ConclusionsWe identified four key renal outcome measures that should be considered for use in perioperative clinical trials. Using standardised definitions to capture and report these endpoints will facilitate improved benchmarking and meta-analysis of future trials.