Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study.

PURPOSE: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. METHODS: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. RESULTS: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1-3) days vs. 3 (Q1-Q3, 1-6) days) and hospital length of stay (median 14 (Q1-Q3, 9-24) days vs. 10 (Q1-Q3, 7-17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. CONCLUSION: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide.

Prevention of Cardiac Surgery-Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial.

BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction. STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines. SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms. SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI. DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis. ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses. RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively. LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

Biomarker-guided implementation of the KDIGO guidelines to reduce the occurrence of acute kidney injury in patients after cardiac surgery (PrevAKI-multicentre): protocol for a multicentre, observational study followed by randomised controlled feasibility trial.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial. METHODS AND ANALYSIS: We plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes. ETHICS AND DISSEMINATION: The PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial. TRIAL REGISTRATION NUMBER: NCT03244514.

A Multinational Observational Study Exploring Adherence With the Kidney Disease: Improving Global Outcomes Recommendations for Prevention of Acute Kidney Injury After Cardiac Surgery.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] ±1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD ±1.1] vs 3.5 [SD ±1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.

Coagulation abnormalities, bleeding, thrombosis, and management of patients with acute liver failure in Australia and New Zealand.

BACKGROUND AND AIM: To study the management of coagulation and hematological derangements among severe acute liver failure (ALF) patients in Australia and New Zealand liver transplant intensive care units (ICUs). METHODS: Analysis of key baseline characteristics, etiology, coagulation and hematological tests, use of blood products, thrombotic complications, and clinical outcomes during the first ICU week. RESULTS: We studied 62 ALF patients. The first day median peak international normalized ratio was 5.5 (inter-quartile range [IQR] 3.8-8.7), median longest activated partial thromboplastin time was 62 s (IQR 44-87), and median lowest fibrinogen was 1.1 (IQR 0.8-1.6) g/L. Fibrinogen was only measured in 85% of patients, which was less than other tests (P < 0.0001). Median initial lowest platelet count was 83 (IQR 41-122) × 109 /L. Overall, 58% of patients received fresh frozen plasma, 40% cryoprecipitate, 35% platelets, and 15% prothrombin complex concentrate. Patients with bleeding complications (19%) had more severe overall hypofibrinogenemia and thrombocytopenia. Thrombotic complications were less common (10% of patients), were not associated with consistent patterns of abnormal hemostasis, and were not immediately preceded by clotting factor administration and half occurred only after liver transplantation surgery. CONCLUSION: In ALF patients admitted to dedicated Australia and New Zealand ICUs, fibrinogen was measured less frequently than other coagulation parameters but, together with platelets, appeared more relevant to bleeding risk. Blood products and procoagulant factors were administered to most patients at variable levels of hemostatic derangement, and bleeding complications were more common than thrombotic complications. This epidemiologic information and practice variability provide baseline data for the design and powering of interventional studies.

Urinary Neutrophil Gelatinase-Associated Lipocalin as Predictor of Short- or Long-Term Outcomes in Cardiac Surgery Patients.

OBJECTIVES: To determine the ability of urinary neutrophil gelatinase-associated lipocalin (uNGAL) to predict cardiac surgery-associated acute kidney injury (CSA-AKI), continuous renal replacement therapy (CRRT), mortality, and a composite outcome of major adverse kidney events at 365 days (MAKE365), and to investigate the influence of cardiopulmonary bypass (CPB) on NGAL release. DESIGN: A prospective observational study. SETTING: A single-center university hospital. PARTICIPANTS: A cohort of 288 adult cardiac surgery patients. INTERVENTIONS: uNGAL was measured at baseline, immediately after surgery, and on days 1 and 2 postoperatively. The authors used the recent Kidney Disease Improving Global Outcomes consensus criteria to define CSA-AKI. MEASUREMENTS AND MAIN RESULTS: CSA-AKI occurred in 36.1% of patients. uNGAL rapidly became significantly higher in patients who developed AKI, with peak value immediately after surgery (349.9 [76.6-1446.6] v 90.1 [20.8-328] ng/mg creatinine; p<0.001). No measure of uNGAL (peak, postsurgery, day 1 or 2 postsurgery) accurately predicted CSA-AKI, CRRT, mortality, or MAKE365. However, immediately after surgery, CPB induced greater uNGAL release compared with off-pump surgery (265.5 µmol/L [71-989.6] v 48.7 ng/mg creatinine [17-129.8]; p<0.001). Moreover, such early uNGAL release correlated with CPB duration (r = 0.505; p<0.001) but not with peak serum creatinine values on day 3 or 7 after surgery. CONCLUSIONS: uNGAL had a limited predictive ability for CSA-AKI or other relevant clinical outcomes after cardiac surgery and appeared to be more closely related to the use and duration of CPB. Thus, its levels may represent the aggregate effect of an inflammatory response to CPB as well as a renal response to cardiac surgery and inflammation.