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TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors.

ABSTRACT: Acute kidney injury (AKI) is a common complication after cardiopulmonary resuscitation (CPR) and predicts in-hospital mortality. To which extent post-resuscitation disease or the initial event of cardiac arrest and the duration of insufficient cardiac output triggers AKI is challenging to discriminate. Knowledge on molecular mediators of AKI is scarce. Early identification of patients at high risk of AKI is hampered by the low sensitivity of the established tests in clinical routine practice. The present study aimed to determine the diagnostic utility of the novel urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) for the early recognition of AKI in patients with non-traumatic shock.The performance of [TIMP-2]·[IGFBP7] was prospectively analysed in 48 patients with shock following out-of-hospital cardiac arrest (OHCA). All patients were treated with target temperature management (TTM) for 24 h. Urinary [TIMP-2]·[IGFBP7] samples were collected at 3 and 24 h after determination of OHCA.Patients (n = 31 (65%)) developed AKI after an average of 26?± 12 h. Patients who developed AKI had significantly higher [TIMP-2]·[IGFBP7] compared to individuals that did not develop AKI (1.52?±?0.13 vs. 0.13?±?0.14; p

SUBMITTER: Adler C

PROVIDER: S-EPMC5948851 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors.

Adler Christoph C Heller Tobias T Schregel Felix F Hagmann Henning H Hellmich Martin M Adler Joana J Reuter Hannes H

Critical care (London, England) 20180512 1

<h4>Background</h4>Acute kidney injury (AKI) is a common complication after cardiopulmonary resuscitation (CPR) and predicts in-hospital mortality. To which extent post-resuscitation disease or the initial event of cardiac arrest and the duration of insufficient cardiac output triggers AKI is challenging to discriminate. Knowledge on molecular mediators of AKI is scarce. Early identification of patients at high risk of AKI is hampered by the low sensitivity of the established tests in clinical r ...[more]

PMID: 29751827

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Project description:ImportanceMany children with return of spontaneous circulation (ROSC) following cardiac arrest (CA) experience acute kidney injury (AKI). The impact of therapeutic hypothermia on the epidemiology of post-CA AKI in children has not been fully investigated.ObjectiveThe study aims were to: 1) describe the prevalence of severe AKI in comatose children following out-of-hospital CA (OHCA), 2) identify risk factors for severe AKI, 3) evaluate the impact of therapeutic hypothermia on the prevalence of severe AKI, and 4) evaluate the association of severe AKI with survival and functional outcomes.DesignA post hoc secondary analysis of data from the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial.SettingThirty-six pediatric intensive care units in the United States and Canada.ParticipantsOf 282 eligible subjects with an initial creatinine obtained within 24 h of randomization, 148 were randomized to therapeutic hypothermia and 134 were randomized to therapeutic normothermia.Main outcomes and measuresPrimary outcome was prevalence of severe AKI, as defined by stage 2 and 3 Kidney Disease Improving Global Outcomes (KDIGO) consensus definition; secondary outcome was survival with a favorable neurobehavioral outcome. For this study, risk factors and outcomes were compared between those with/without severe AKI.ResultsOf the 282 subjects enrolled, 180 (64%) developed AKI of which 117 (41% of all enrolled) developed severe AKI. Multivariable modeling found younger age, longer duration of chest compressions, higher lactate level at time of temperature intervention and higher number of vasoactive agents through day 1 of intervention associated with severe AKI. There was no difference in severe AKI between therapeutic hypothermia (39.9%) and therapeutic normothermia (43.3%) groups (p = 0.629). Survival was lower in those with severe AKI at 28 days (21% vs no severe AKI 49%, p < 0.001) and 12 months (21% vs no severe AKI 42%, p < 0.001). One year survival with favorable functional outcome was lower in those with severe AKI.Conclusions and relevanceSevere AKI occurs frequently in children with ROSC after OHCA, especially in younger children and those with higher initial lactates and hemodynamic support. Severe AKI was associated with worse survival and functional outcome. Therapeutic hypothermia did not reduce the incidence of severe AKI.

Project description:Background: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). Aims: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. Methods: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurologically favorable outcome (Cerebral Performance Category [CPC] = 1-2) vs unfavorable outcome (CPC>2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. Results: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (Specificity=88%; Hit Rate=83%). Conclusions: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.

Project description:BackgroundAcute kidney injury (AKI) is a frequent complication in cardiac arrest survivors and associated with adverse outcome. It remains unclear whether the incidence of AKI increases after the post-cardiac arrest contrast administration for coronary angiography and whether this depends on timing of angiography. Aim of this study was to investigate whether early angiography is associated with increased development of AKI compared to deferred angiography in out-of-hospital cardiac arrest (OHCA) survivors.MethodsIn this retrospective multicenter cohort study, we investigated whether early angiography (within 2 h) after OHCA was non-inferior to deferred angiography regarding the development of AKI. We used an absolute difference of 5% as the non-inferiority margin. Primary non-inferiority analysis was done by calculating the risk difference with its 90% confidence interval (CI) using a generalized linear model for a binary outcome. As a sensitivity analysis, we repeated the primary analysis using propensity score matching. A multivariable model was built to identify predictors of acute kidney injury.ResultsA total of 2375 patients were included from 2009 until 2018, of which 1148 patients were treated with early coronary angiography and 1227 patients with delayed or no angiography. In the early angiography group 18.5% of patients developed AKI after OHCA and 24.1% in the deferred angiography group. Risk difference was - 3.7% with 90% CI ranging from - 6.7 to - 0.7%, indicating non-inferiority of early angiography. The sensitivity analysis using propensity score matching showed accordant results, but no longer non-inferiority of early angiography. The factors time to return of spontaneous circulation (odds ratio [OR] 1.12, 95% CI 1.06-1.19, p < 0.001), the (not) use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (OR 0.20, 95% CI 0.04-0.91, p = 0.04) and baseline creatinine (OR 1.05, 95% CI 1.03-1.07, p < 0.001) were found to be independently associated with the development of AKI.ConclusionsAlthough AKI occurred in approximately 20% of OHCA patients, we found that early angiography was not associated with a higher AKI incidence than a deferred angiography strategy. The present results implicate that it is safe to perform early coronary angiography with respect to the risk of developing AKI after OHCA.

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TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors.

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TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors.

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