Daily fluctuations in kidney function in critically ill adults.
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ABSTRACT:
SUBMITTER: Huang CY
PROVIDER: S-EPMC9644484 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
Daily fluctuations in kidney function in critically ill adults.
Huang Chao-Yuan CY Güiza Fabian F De Vlieger Greet G Meyfroidt Geert G
Critical care (London, England) 20221109 1
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Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator
2015-10-24 | E-GEOD-74224 | biostudies-arrayexpress
Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples
2015-10-24 | GSE74224 | GEO
Project description:BackgroundThe epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury.MethodsWe used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality.ResultsA total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output.ConclusionsAcute kidney injury is common and is associated with poor outcomes, including increased mortality, among critically ill children and young adults. (Funded by the Pediatric Nephrology Center of Excellence at Cincinnati Children's Hospital Medical Center and others; AWARE ClinicalTrials.gov number, NCT01987921 .).
| S-EPMC5322803 | biostudies-literature
Project description:ObjectivesAcute kidney injury is common among the critically ill. However, the incidence, medication use, and outcomes of acute kidney injury have been variably described. We conducted a single-center, retrospective cohort study to examine the risk factors and correlates associated with acute kidney injury in critically ill adults with a particular focus on medication class usage.MethodsWe reviewed the electronic medical records of all adult patients admitted to an intensive care unit between 1 February and 30 August 2020. Acute kidney injury was defined by the 2012 Kidney Disease: Improving Global Outcomes guidelines. Data included were demographics, comorbidities, symptoms, laboratory parameters, interventions, and outcomes. The primary outcome was acute kidney injury incidence. A Least Absolute Shrinkage and Selection Operator regression model was used to determine risk factors associated with acute kidney injury. Secondary outcomes including acute kidney injury recovery and intensive care unit mortality were analyzed using a Cox regression model.ResultsAmong 226 admitted patients, 108 (47.8%) experienced acute kidney injury. 37 (34.3%), 39 (36.1%), and 32 patients (29.6%) were classified as acute kidney injury stages I-III, respectively. Among the recovery and mortality cohorts, analgesics/sedatives, anti-infectives, and intravenous fluids were significant (p-value < 0.05). The medication classes IV-fluid electrolytes nutrition (96.7%), gastrointestinal (90.2%), and anti-infectives (81.5%) were associated with an increased odds of developing acute kidney injury, odd ratios: 1.27, 1.71, and 1.70, respectively. Cox regression analyses revealed a significantly increased time-varying mortality risk for acute kidney injury-stage III, hazard ratio: 4.72 (95% confidence interval: 1-22.33). In the recovery cohort, time to acute kidney injury recovery was significantly faster in stage I, hazard ratio: 9.14 (95% confidence interval: 2.14-39.06) cohort when compared to the stage III cohort.ConclusionEvaluation of vital signs, laboratory, and medication use data may be useful to determine acute kidney injury risk stratification. The influence of particular medication classes further impacts the risk of developing acute kidney injury, necessitating the importance of examining pharmacotherapeutic regimens for early recognition of renal impairment and prevention.
| S-EPMC9150243 | biostudies-literature
Project description:Background and objectivesAcute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score.Design, setting, participants, & measurementsData from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers.ResultsThe 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively.ConclusionsOur new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations.
| S-EPMC3359007 | biostudies-literature
Project description:Prediction of major adverse kidney events in critically ill patients may help target therapy, allow risk adjustment, and facilitate the conduct of clinical trials. In a cohort comprised of all critically ill adults admitted to five intensive care units at a single tertiary care center over one year, we developed a logistic regression model for the outcome of Major Adverse Kidney Events within 30 days (MAKE30), the composite of persistent renal dysfunction, new renal replacement therapy (RRT), and in-hospital mortality. Proposed risk factors for the MAKE30 outcome were selected a priori and included age, race, gender, University Health System Consortium (UHC) expected mortality, baseline creatinine, volume of isotonic crystalloid fluid received in the prior 24 h, admission service, intensive care unit (ICU), source of admission, mechanical ventilation or receipt of vasopressors within 24 h of ICU admission, renal replacement therapy prior to ICU admission, acute kidney injury, chronic kidney disease as defined by baseline creatinine value, and renal failure as defined by the Elixhauser index. Among 10,983 patients in the study population, 1489 patients (13.6%) met the MAKE30 endpoint. The strongest independent predictors of MAKE30 were UHC expected mortality (OR 2.32 [95%CI 2.06-2.61]) and presence of acute kidney injury at ICU admission (OR 4.98 [95%CI 4.12-6.03]). The model had strong predictive properties including excellent discrimination with a bootstrap-corrected area-under-the-curve (AUC) of 0.903, and high precision of calibration with a mean absolute error prediction of 1.7%. The MAKE30 composite outcome can be reliably predicted from factors present within 24 h of ICU admission using data derived from the electronic health record.
| S-EPMC5821255 | biostudies-literature
Project description:Urine neutrophil gelatinase-associated lipocalin (uNGAL) has shown promise as a biomarker for the early detection of acute kidney injury (AKI) in fixed models of injury, but its ability to predict AKI and provide prognostic information in critically ill adults is unknown. We prospectively studied a heterogeneous population of 451 critically ill adults, 64 (14%) and 86 (19%) of whom developed AKI within 24 and 48 h of enrollment, respectively. Median uNGAL at enrollment was higher among patients who developed AKI within 48 h compared with those who did not (190 versus 57 ng/mg creatinine, P < 0.001). The areas under the receiver operating characteristic curves describing the relationship between uNGAL level and the occurrence of AKI within 24 and 48 h were 0.71 (95% Confidence Intervals [CI]: 0.63 to 0.78) and 0.64 (95% CI: 0.57 to 0.71), respectively. Urine neutrophil gelatinase-associated lipocalin remained independently associated with the development of AKI after adjustment for age, serum creatinine closest to enrollment, illness severity, sepsis, and intensive care unit (ICU) location, although it only marginally improved the predictive performance of the clinical model alone. A Cox proportional hazards model using time to first dialysis, adjusted for APACHE II score, suggested that uNGAL independently predicts severe AKI during hospitalization [HR 2.60, 95% CI:1.55 to 4.35]. In summary, although a single measurement of uNGAL exhibited moderate predictive utility for the development and severity of AKI in a heterogeneous ICU population, its additional contribution to conventional clinical risk predictors appears limited.
| S-EPMC2723988 | biostudies-literature
Project description:Oxygen supplementation is one of the most common interventions in critically ill patients. Despite over a century of data suggesting both beneficial and detrimental effects of supplemental oxygen, optimal arterial oxygenation targets in adult patients remain unclear. Laboratory animal studies have consistently showed that exposure to a high FiO2 causes respiratory failure and early death. Human autopsy studies from the 1960s purported to provide histologic evidence of pulmonary oxygen toxicity in the form of diffuse alveolar damage. However, concomitant ventilator-induced lung injury and/or other causes of acute lung injury may explain these findings. Although some observational studies in general populations of critically adults showed higher mortality in association with higher oxygen exposures, this finding has not been consistent. For some specific populations, such as those with cardiac arrest, studies have suggested harm from targeting supraphysiologic PaO2 levels. More recently, randomized clinical trials of arterial oxygenation targets in narrower physiologic ranges were conducted in critically ill adult patients. Although two smaller trials came to opposite conclusions, the two largest of these trials showed no differences in clinical outcomes in study groups that received conservative versus liberal oxygen targets, suggesting that either strategy is reasonable. It is possible that some strategies are of benefit in some subpopulations, and this remains an important ongoing area of research. Because of the ubiquity of oxygen supplementation in critically ill adults, even small treatment effects could have a large impact on a global scale.
| S-EPMC8521700 | biostudies-literature
Project description:ObjectivesTo understand the influence of prehospital physical function and strength on clinical outcomes of critically ill older adults.DesignSecondary analysis of prospective cohort study.SettingHealth, Aging and Body Composition (Health ABC) Study.ParticipantsOf 3,075 older adult Health ABC participants, we identified 575 (60% white, 61% male, mean age 79) with prehospital function or grip strength measurements within 2 years of an intensive care unit stay.MeasurementsThe primary analysis evaluated the association between prehospital walk speed and mortality, and secondary analyses focused on associations between function or grip strength and mortality or hospital length of stay. Function and grip strength were analyzed as continuous and categorical predictors.ResultsSlower prehospital walk speed was associated with greater risk of 30-day mortality (for each 0.1 m/s slower, odds ratio = 1.13, 95% confidence interval (CI) = 1.04-1.23, P = .004). Grip strength, chair stands, and balance had weaker, non-statistically significant associations with 30-day mortality. Participants with slower prehospital walk speed (hazard ratio (HR) = 0.94, 95% CI = 0.90-0.98, P = .005) and weak grip strength (HR = 0.85, 95% CI = 0.73-0.99, P = .03) were less likely to be discharged from the hospital alive. All function and strength measures were significantly associated with 1-year mortality.ConclusionSlow prehospital walk speed was strongly associated with greater 30-day mortality and longer hospital stay in critically ill older adults, and measures of function and strength were associated with 1-year mortality. These data add to the accumulating evidence on the relationship between physical function and critical care outcomes.
| S-EPMC5928515 | biostudies-literature
Project description:BackgroundWe aimed to study the association of suspected versus confirmed infection with the novel SARS-CoV2 virus with the prevalence of acute kidney injury (AKI) in critically ill children.MethodsSequential point-prevalence study of children and young adults aged 7 days to 25 years admitted to intensive care units under investigation for SARS-CoV2 infection. AKI was staged in the first 14 days of enrollment using KDIGO creatinine-based staging. SARS-CoV2 positive (CONFIRMED) were compared to SUSPECTED (negative or unknown). Outcome data was censored at 28-days.ResultsIn 331 patients of both sexes, 179 (54.1%) were CONFIRMED, 4.2% (14) died. AKI occurred in 124 (37.5%) and severe AKI occurred in 63 (19.0%). Incidence of AKI in CONFIRMED was 74/179 (41.3%) versus 50/152 (32.9%) for SUSPECTED; severe AKI occurred in 35 (19.6%) of CONFIRMED and 28 (18.4%) of SUSPECTED. Mortality was 6.2% (n = 11) in CONFIRMED, but 9.5% (n = 7) in those CONFIRMED with AKI. On multivariable analysis, only Hispanic ethnicity (relative risk 0.5, 95% CI 0.3-0.9) was associated with less AKI development among those CONFIRMED.ConclusionsAKI and severe AKI occur commonly in critically ill children with SARS-CoV2 infection, more than double the historical standard. Further investigation is needed during this continuing pandemic to describe and refine the understanding of pediatric AKI epidemiology and outcomes.Trial registrationNCT01987921.ImpactWhat is the key message of the article? AKI occurs in children exposed to the novel SARS-CoV2 virus at high prevalence (~40% with some form of AKI and 20% with severe AKI). What does it add to the existing literature? Acute kidney injury (AKI) occurs commonly in adult patients with SARS-CoV2 (COVID), very little data describes the epidemiology of AKI in children exposed to the virus. What is the impact? A pediatric vaccine is not available; thus, the pandemic is not over for children. Pediatricians will need to manage significant end-organ ramifications of the novel SARS-CoV2 virus including AKI.
| S-EPMC8323541 | biostudies-literature