Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL).

PURPOSE: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety. METHODS: In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition. RESULTS: Six hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0-24] and 14 [0-24], number of days alive and discharged from the ICU through day 28 were 15 [0-22] and 10 [0-22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group. CONCLUSION: Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified.

Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases.

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Moving toward a contemporary classification of drug-induced kidney disease.

Drug-induced kidney disease (DIKD) accounts for about one-fourth of all cases of acute kidney injury (AKI) in hospitalized patients, especially in critically ill setting. There is no standard definition or classification system of DIKD. To address this, a phenotype definition of DIKD using expert consensus was introduced in 2015. Recently, a novel framework for DIKD classification was proposed that incorporated functional change and tissue damage biomarkers. Medications were stratified into four categories, including "dysfunction without damage," "damage without dysfunction," "both dysfunction and damage," and "neither dysfunction nor damage" using this novel framework along with predominant mechanism(s) of nephrotoxicity for drugs and drug classes. Here, we briefly describe mechanisms and provide examples of drugs/drug classes related to the categories in the proposed framework. In addition, the possible movement of a patient's kidney disease between certain categories in specific conditions is considered. Finally, opportunities and barriers to adoption of this framework for DIKD classification in real clinical practice are discussed. This new classification system allows congruencies for DIKD with the proposed categorization of AKI, offering clarity as well as consistency for clinicians and researchers.

Prevention and management of antibiotic associated acute kidney injury in critically ill patients: new insights.

PURPOSE OF REVIEW: Drug associated kidney injury (D-AKI) occurs in 19-26% of hospitalized patients and ranks as the third to fifth leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Given the high use of antimicrobials in the ICU and the emergence of new resistant organisms, the implementation of preventive measures to reduce the incidence of D-AKI has become increasingly important. RECENT FINDINGS: Artificial intelligence is showcasing its capabilities in early recognition of at-risk patients for acquiring AKI. Furthermore, novel synthetic medications and formulations have demonstrated reduced nephrotoxicity compared to their traditional counterparts in animal models and/or limited clinical evaluations, offering promise in the prevention of D-AKI. Nephroprotective antioxidant agents have had limited translation from animal studies to clinical practice. The control of modifiable risk factors remains pivotal in avoiding D-AKI. SUMMARY: The use of both old and new antimicrobials is increasingly important in combating the rise of resistant organisms. Advances in technology, such as artificial intelligence, and alternative formulations of traditional antimicrobials offer promise in reducing the incidence of D-AKI, while antioxidant medications may aid in minimizing nephrotoxicity. However, maintaining haemodynamic stability using isotonic fluids, drug monitoring, and reducing nephrotoxic burden combined with vigilant antimicrobial stewardship remain the core preventive measures for mitigating D-AKI while optimizing effective antimicrobial therapy.

Precision management of acute kidney injury in the intensive care unit: current state of the art.

Acute kidney injury (AKI) is a prototypical example of a common syndrome in critical illness defined by consensus. The consensus definition for AKI, traditionally defined using only serum creatinine and urine output, was needed to standardize the description for epidemiology and to harmonize eligibility for clinical trials. However, AKI is not a simple disease, but rather a complex and multi-factorial syndrome characterized by a wide spectrum of pathobiology. AKI is now recognized to be comprised of numerous sub-phenotypes that can be discriminated through shared features such as etiology, prognosis, or common pathobiological mechanisms of injury and damage. The characterization of sub-phenotypes can serve to enable prognostic enrichment (i.e., identify subsets of patients more likely to share an outcome of interest) and predictive enrichment (identify subsets of patients more likely to respond favorably to a given therapy). Existing and emerging biomarkers will aid in discriminating sub-phenotypes of AKI, facilitate expansion of diagnostic criteria, and be leveraged to realize personalized approaches to management, particularly for recognizing treatment-responsive mechanisms (i.e., endotypes) and targets for intervention (i.e., treatable traits). Specific biomarkers (e.g., serum renin; olfactomedin 4 (OLFM4); interleukin (IL)-9) may further enable identification of pathobiological mechanisms to serve as treatment targets. However, even non-specific biomarkers of kidney injury (e.g., neutrophil gelatinase-associated lipocalin, NGAL; [tissue inhibitor of metalloproteinases 2, TIMP2]·[insulin like growth factor binding protein 7, IGFBP7]; kidney injury molecule 1, KIM-1) can direct greater precision management for specific sub-phenotypes of AKI. This review will summarize these evolving concepts and recent innovations in precision medicine approaches to the syndrome of AKI in critical illness, along with providing examples of how they can be leveraged to guide patient care.

The Influence of Body Mass Index on Clinical Interpretation of Established and Novel Biomarkers in Acute Heart Failure.

BACKGROUND: Body mass index (BMI) is a known confounder for natriuretic peptides, but its influence on other biomarkers is less well described. We investigated whether BMI interacts with biomarkers' association with prognosis in patients with acute heart failure (AHF). METHODS AND RESULTS: B-type natriuretic peptide (BNP), high-sensitivity cardiac troponin I (hs-cTnI), galectin-3, serum neutrophil gelatinase-associated lipocalin (sNGAL), and urine NGAL were measured serially in patients with AHF during hospitalization in the AKINESIS (Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic Heart Failure) study. Cox regression analysis was used to determine the association of biomarkers and their interaction with BMI for 30-day, 90-day and 1-year composite outcomes of death or HF readmission. Among 866 patients, 21.2%, 29.7% and 46.8% had normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) or obese (≥ 30 kg/m2) BMIs on admission, respectively. Admission values of BNP and hs-cTnI were negatively associated with BMI, whereas galectin-3 and sNGAL were positively associated with BMI. Admission BNP and hs-cTnI levels were associated with the composite outcome within 30 days, 90 days and 1 year. Only BNP had a significant interaction with BMI. When BNP was analyzed by BMI category, its association with the composite outcome attenuated at higher BMIs and was no longer significant in obese individuals. Findings were similar when evaluated by the last-measured biomarkers and BMIs. CONCLUSIONS: In patients with AHF, only BNP had a significant interaction with BMI for the outcomes, with its association attenuating as BMI increased; hs-cTnI was prognostic, regardless of BMI.

Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury.

INTRODUCTION: Sepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound, ilofotase alfa, showed no safety or tolerability concerns in a phase 2 trial. Renal function improvement over 28 days was significantly greater in the ilofotase alfa group. Moreover, a significant relative reduction in 28-day all-cause mortality of >40% was observed. A follow-up trial has been designed to confirm these findings. METHODS AND ANALYSIS: This is a phase 3, global, multi-centre, randomised, double-blind, placebo-controlled, sequential design trial in which patients are randomly assigned to either placebo or 1.6 mg/kg ilofotase alfa. Randomisation is stratified by baseline modified Sequential Organ Failure Assessment (mSOFA) score and trial site. The primary objective is to confirm the survival benefit with ilofotase alfa by demonstrating a reduction in 28-day all-cause mortality in patients with sepsis-associated AKI requiring vasopressors. A maximum of 1400 patients will be enrolled at ∼120 sites in Europe, North America, Japan, Australia and New Zealand. Up to four interim analyses will take place. Based on predefined decision rules, the trial may be stopped early for futility or for effectiveness. In addition, patients with COVID-19 disease and patients with 'moderate to severe' chronic kidney disease are analysed as 2 separate cohorts of 100 patients each. An independent Data Monitoring Committee evaluates safety data at prespecified intervals throughout the trial. ETHICS AND DISSEMINATION: The trial is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will determine the potential of ilofotase alfa to reduce mortality in critically ill patients with sepsis-associated AKI and will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: EudraCT CT Number 2019-0046265-24. US IND Number 117 605 Pre-results. CLINICALTRIALS: gov number: NCT04411472.

Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup.

Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research.

Implications of worsening renal function before hospitalization for acute heart failure.

AIMS: Kidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF). METHODS AND RESULTS: We evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome. CONCLUSIONS: Admission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.

Galectin-3, Acute Kidney Injury and Myocardial Damage in Patients With Acute Heart Failure.

BACKGROUND: Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF). METHODS AND RESULTS: We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death. CONCLUSIONS: In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

Diuretic combinations in critically ill patients with respiratory failure: A systematic review and meta-analysis.

BACKGROUND: In patients with respiratory failure, loop diuretics remain the cornerstone of the treatment to maintain fluid balance, but resistance is common. AIM: To determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure. METHODS: We searched MEDLINE, Embase, Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic. A meta-analysis using mean differences (MD) with 95% confidence interval (CI) was performed for the 24-h fluid balance (primary outcome) and the 24-h urine output, while descriptive statistics were used for safety events. RESULTS: Nine studies totalling 440 patients from a total of 6510 citations were included. When compared to loop diuretics alone, the addition of a second diuretic is associated with an improved negative fluid balance at 24 h [MD: -1.06 L (95%CI: -1.46; -0.65)], driven by the combination of a thiazide plus furosemide [MD: -1.25 L (95%CI: -1.68; -0.82)], while no difference was observed with the combination of a loop-diuretic plus acetazolamide [MD: -0.40 L (95%CI: -0.96; 0.16)] or spironolactone [MD: -0.65 L (95%CI: -1.66; 0.36)]. Heterogeneity was high and the report of clinical and safety endpoints varied across studies. CONCLUSION: Based on limited evidence, the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure, but only when using a thiazide. Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.

Clinical Implementation of NGAL Testing to Improve Diagnostic Assessment of AKI Episodes in a Canadian Center.

Background: The differential diagnosis of acute kidney injury (AKI) episodes is often challenging. Novel AKI biomarkers have shown their utility to improve prognostic prediction and diagnostic assessment in various research populations but their implementation in standard clinical practice is still rarely reported. Objective: To report the differential diagnostic ability and associated clinical utility of the neutrophil gelatinase-associated lipocalin (NGAL) testing in a real-life setting of a heterogeneous AKI population. Design: This is a retrospective cohort study combined with a clinical audit using questionnaires distributed to consultant nephrologists following NGAL results. Setting: The first 250 consecutive patients with a confirmed AKI where an NGAL test (plasma NGAL [pNGAL] or urine NGAL [uNGAL]) was ordered from a large academic center in Montreal, Canada from January 2021 to August 2021. Patients: Patients were classified into 3 groups based on the final AKI etiology category (functional, intrarenal, and postrenal) following definitive adjudication by 2 independent nephrologists. Methods: The ability of plasma NGAL (pNGAL), urine NGAL (uNGAL), and uNGAL-to-creatinine ratio (uNGAL/Cr) to discriminate intrarenal from functional AKI etiologies was compared to standard urine chemistry (FENa) and proteinuria. A logistic regression was used to evaluate the association between intrarenal AKI and increased biomarker levels. The overall clinical utility and appreciation of the NGAL test was evaluated using a questionnaire completed prospectively by the consultant nephrologist at the time of receiving the NGAL result. The NGAL results were prospectively available to clinicians with a median time of 2.9 (1.3-7.4) hours from the initial order. Results: A total of 214 uNGAL and 44 pNGAL were ordered from 100 functional, 139 intrarenal and 11 postrenal AKI episodes after final adjudication. The discriminative ability of FENa (AUC 0.68 [95% CI: 0.61-0.75]) was lower than uNGAL (AUC 0.80 [95% CI: 0.73-0.86]) and uNGAL/Cr (AUC 0.83 [95% CI: 0.77-0.88]) but better than pNGAL (AUC 0.66 [95% CI: 0.48-0.85]). According to consultant nephrologists, the NGAL testing has led to a change in clinical management in 42% of cases. Limitations: Data reported came from a single center and NGAL was reserved for more complex cases, which limits generalizability. No biopsy has been performed for most AKI cases as the final adjudication was based on a retrospective review of the hospitalization episode. Conclusions: Neutrophil gelatinase-associated lipocalin testing can be successfully integrated as part of the diagnostic workup for AKI in clinical practice. The integration of tubular damage biomarkers to functional biomarkers can further improve the differential diagnostic assessment. However, the impact of such biomarkers on AKI management and associated outcomes still needs further validation.

Contexte: Le diagnostic différentiel des épisodes d'insuffisance rénale aiguë (IRA) pose souvent un problème. De nouveaux biomarqueurs d'IRA ont montré leur utilité pour améliorer la prédiction pronostique et l'évaluation diagnostique dans diverses populations de recherche, mais leur application dans la pratique clinique est encore peu rapportée. Objectif: Rendre compte de la capacité de diagnostic différentiel et de l'utilité clinique du test NGAL (neutrophil gelatinase-associated lipocalin) dans le contexte réel d'une population hétérogène de patients atteints d'IRA. Devis: Étude de cohorte rétrospective combinée à un audit clinique mené par l'entremise de questionnaires distribués aux néphrologues consultants à la suite du résultat NGAL. Cadre: Les 250 premiers patients consécutifs avec une IRA confirmée, pour qui un test NGAL (plasmatique [pNGAL] ou urinaire [uNGAL]) avait été demandé entre janvier et août 2021 dans un grand centre universitaire de Montréal (Canada). Sujets: Les patients ont été classés en 3 groupes selon la catégorie étiologique finale de l'IRA (fonctionnelle, intrarénale, post-rénale) après révision par deux néphrologues indépendants. Méthodologie: La capacité du pNGAL, du uNGAL et du rapport uNGAL et du rapport uNGAL sur créatinine (uNGAL/Cr) à discriminer les étiologies fonctionnelles des étiologies intrarénales a été comparée à celle des indices urinaires standard de l'urine (FENa) et de la protéinurie. Une régression logistique a servi à évaluer l'association entre l'IRA intrarénale et la hausse des taux des biomarqueurs. L'appréciation du test NGAL et son utilité clinique globale ont été évaluées à l'aide d'un questionnaire rempli prospectivement par le néphrologue consultant lors de la réception du résultat NGAL. Les résultats NGAL ont été mis à la disposition des cliniciens de manière prospective, dans un délai médian de 2,9 [1,3-7,4] heures suivant la prescription initiale. Résultats: En tout, après la révision finale, 214 tests uNGAL et 44 tests pNGAL ont été demandés à partir de 100 épisodes d'IRA fonctionnelle, 139 épisodes d'IRA intrarénale et 11 épisodes d'IRA post-rénale. La capacité discriminante du FENa (SSC: 0,68 [IC 95 %: 0,61-0,75]) était inférieure à celles du uNGAL (SSC: 0,80 [IC 95 %: 0,73-0,86]) et du rapport uNGAL/ Cr (SSC: 0,83 [IC 95 %: 0,77-0,88]), mais supérieure à celle du pNGAL (SSC: 0,66 [IC 95 %: 0,48-0,85]). Les néphrologues ont indiqué que les tests NGAL avaient entraîné un changement dans la prise en charge clinique dans 42 % des cas. Limites: Les données provenaient d'un seul centre et le test NGAL était réservé aux cas plus complexes, ce qui limite la généralisabilité. Dans la plupart des cas, aucune biopsie n'a été effectuée et le diagnostic final était basé sur un examen rétrospectif de l'hospitalisation. Conclusions: En pratique clinique, les tests NGAL peuvent être intégrés avec succès au diagnostic de l'IRA. L'intégration des biomarqueurs de lésions tubulaires aux biomarqueurs fonctionnels peut améliorer davantage l'évaluation du diagnostic différentiel. Cependant, l'impact de ces biomarqueurs sur la prise en charge de l'IRA et les résultats connexes doit encore être validé.

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma.