Dataset Information

Azithromycin and Major Adverse Kidney Events in Critically Ill Patients With Sepsis-Associated Acute Kidney Injury.

ABSTRACT:

Background

Sepsis-associated acute kidney injury (SA-AKI) is associated with significant morbidity and mortality. Immune dysregulation is a hallmark of sepsis, with important contributions to organ dysfunction including injury and repair mechanisms in AKI. Macrolide antibiotics, such as azithromycin, have previously demonstrated in preclinical models a myriad of immunomodulatory effects that may benefit critically ill patients with SA-AKI. The aim of this study was to determine if early receipt of azithromycin in SA-AKI is associated with a reduction in major adverse kidney events (MAKE) at hospital discharge.

Methods

This was a single center, retrospective cohort study of critically ill adult patients with SA-AKI. Early exposure to azithromycin was defined as receipt of one or more doses within 48 h of a hospital admission with SA-AKI. The primary outcome of MAKE assessed at hospital discharge was the composite of death, requirement for kidney replacement therapy, or a decline in estimated glomerular filtration rate of 25% or more. Multivariable logistic regression was used to account for potential confounders in the assessment.

Results

Of 737 included patients with SA-AKI, 152 (20.6%) received azithromycin. Patients that received early azithromycin were less likely to experience MAKE at hospital discharge when compared to those patients not receiving azithromycin: 38.8% versus 48.4% (P = 0.035). In multivariable logistic regression, receipt of azithromycin was independently associated with a decreased odds of MAKE at hospital discharge (aOR 0.62, 95% CI 0.41-0.93).

Conclusions

Early exposure to azithromycin in SA-AKI is independently associated with lower odds of MAKE at hospital discharge.

SUBMITTER: Behal ML

PROVIDER: S-EPMC9725110 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Azithromycin and Major Adverse Kidney Events in Critically Ill Patients With Sepsis-Associated Acute Kidney Injury.

Behal Michael L ML Nguyen Jonny L JL Li Xilong X Feola David J DJ Neyra Javier A JA Flannery Alexander H AH

Shock (Augusta, Ga.) 20220401 4

<h4>Background</h4>Sepsis-associated acute kidney injury (SA-AKI) is associated with significant morbidity and mortality. Immune dysregulation is a hallmark of sepsis, with important contributions to organ dysfunction including injury and repair mechanisms in AKI. Macrolide antibiotics, such as azithromycin, have previously demonstrated in preclinical models a myriad of immunomodulatory effects that may benefit critically ill patients with SA-AKI. The aim of this study was to determine if early ...[more]

PMID: 34731096

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Project description:Rationale & objectiveRisk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI.Study designMulticenter cohort study.Setting & participants9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays.PredictorsMultimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay.Outcomes(1) Hospital mortality and (2) MAKE, defined as the composite of death during hospitalization or within 120 days of discharge, receipt of kidney replacement therapy in the last 48 hours of hospital stay, initiation of maintenance kidney replacement therapy within 120 days, or a ≥50% decrease in estimated glomerular filtration rate from baseline to 120 days from hospital discharge.Analytical approachFour machine-learning algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) and the SHAP (Shapley Additive Explanations) framework were used for feature selection and interpretation. Model performance was evaluated by 10-fold cross-validation and external validation.ResultsOne developed model including 15 features outperformed the SOFA (Sequential Organ Failure Assessment) score for the prediction of hospital mortality, with areas under the curve of 0.79 (95% CI, 0.79-0.80) and 0.71 (95% CI, 0.71-0.71) in the development cohort and 0.74 (95% CI, 0.73-0.74) and 0.71 (95% CI, 0.71-0.71) in the validation cohort (P < 0.001 for both). A second developed model including 14 features outperformed KDIGO (Kidney Disease: Improving Global Outcomes) AKI severity staging for the prediction of MAKE: 0.78 (95% CI, 0.78-0.78) versus 0.66 (95% CI, 0.66-0.66) in the development cohort and 0.73 (95% CI, 0.72-0.74) versus 0.67 (95% CI, 0.67-0.67) in the validation cohort (P < 0.001 for both).LimitationsThe models are applicable only to critically ill adult patients with incident AKI within the first 3 days of an ICU stay.ConclusionsThe reported clinical models exhibited better performance for mortality and kidney recovery prediction than standard scoring tools commonly used in critically ill patients with AKI in the ICU. Additional validation is needed to support the utility and implementation of these models.Plain-language summaryAcute kidney injury (AKI) occurs commonly in critically ill patients admitted to the intensive care unit (ICU) and is associated with high morbidity and mortality rates. Prediction of mortality and recovery after an episode of AKI may assist bedside decision making. In this report, we describe the development and validation of a clinical model using data from the first 3 days of an ICU stay to predict hospital mortality and major adverse kidney events occurring as long as 120 days after hospital discharge among critically ill adult patients who experienced AKI within the first 3 days of an ICU stay. The proposed clinical models exhibited good performance for outcome prediction and, if further validated, could enable risk stratification for timely interventions that promote kidney recovery.

Project description:BackgroundSeveral biomarkers of AKI have been examined for their ability to predict AKI before serum creatinine. Few studies have focused on using kidney biomarkers to better predict major adverse kidney events (MAKE), an increasingly used composite outcome in critical care nephrology research.MethodsSingle-center prospective study collecting blood and urine samples from critically ill patients with AKI Kidney Disease Improving Global Outcomes stage 2 or above, and matched controls from a single, tertiary care intensive care unit (ICU). Samples were collected at 24-48 hours after AKI diagnosis (patients) or ICU admission (controls), 5-7 days later, and 4-6 weeks after discharge for patients with AKI. The primary outcome of interest was MAKE at hospital discharge (MAKE-DC), consisting of the composite end point of death, RRT dependence, or a decrease in estimated glomerular filtration to <75% of baseline.ResultsSerum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary cystatin C, and urinary kidney injury molecule-1 early in the AKI or ICU course were all significantly higher in patients with MAKE-DC compared with those not experiencing MAKE-DC. Additionally, serum/urinary NGAL and serum cystatin C measurements at the first time point remained significantly associated with MAKE events at 3, 6, and 12 months. Serum cystatin C, and to a lesser extent serum NGAL, significantly improved upon a logistic regression clinical prediction model of MAKE-DC (AUROC 0.94 and 0.87 versus 0.83; P=0.001 and P=0.02, respectively). Patients without MAKE-DC experienced a greater decline in serum NGAL from first to second measurement than those patients experiencing MAKE-DC.ConclusionsEarly measures of kidney biomarkers in patients who are critically ill are associated with MAKE-DC. This relationship appears to be greatest with serum NGAL and cystatin C, which display additive utility to a clinical prediction model. Trending serum NGAL may also have utility in predicting MAKE-DC.

Project description: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.

Project description:BACKGROUND:Acute kidney injury (AKI) is a common problem in critically ill patients and associated with high rates of morbidity and mortality. Recently, Major Adverse Kidney Events (MAKE) were introduced as important kidney endpoints. If these endpoints can be predicted, then it may help the physicians to identify high-risk patients and provide the opportunity to have targeted preventive therapy. The objective of this study was to create a simplified scoring system to predict MAKE within 28 days among AKI patients in ICU. METHODS:This is a prospective web-based multicenter cohort study that was conducted in adults who were admitted to the ICU in 17 centers across Thailand from 2013 to 2015. A predicting score was derived from the regression equation with Receiver Operating Characteristic (ROC) analysis to evaluate the diagnostic test and produce predictive models. Internal validation was obtained using the bootstrapping method. RESULTS:From 5071 cases, 2856 (56%) had AKI. Among those with AKI, 1749 (61%) had MAKE. Among those that have MAKE, there were 1175 (41.4%) deaths, 414 (14.4%) were on dialysis and 1154 (40.7%) had non-recovery renal function. The simplified score points of low Glasgow coma scale was 3, tachypnea was 1, vasopressor use was 1, on mechanical ventilation was 2, oliguria was 2, serum creatinine rising ≥ 3 times was 5, high blood urea nitrogen was 3, low hematocrit was 2, and thrombocytopenia was 1. The area under ROC curve for optimism corrected performance was 0.80 (0.78, 0.81). When the cut-off value was 7, the sensitivity, specificity, positive likelihood ratio, and positive predictive values were 0.75, 0.76, 3.10, and 0.84, respectively. When the scoring system was calibrated, the α intercept and β slope were 1.001 and 0, respectively. CONCLUSIONS:SEA-MAKE scoring system is a new simplified clinical tool that can be used to predict major adverse kidney events in AKI patients. The simplicity of the scoring system is highly likely to be used in resource-limited settings. However, external validation is necessary before widespread use.

Project description:Background and objectivesMajor 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.Design, setting, participants, & measurementsWe 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.ResultsOf 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.ConclusionsIn children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.

Dataset Information

Azithromycin and Major Adverse Kidney Events in Critically Ill Patients With Sepsis-Associated Acute Kidney Injury.

Background

Methods

Results

Conclusions

Publications

Azithromycin and Major Adverse Kidney Events in Critically Ill Patients With Sepsis-Associated Acute Kidney Injury.

Similar Datasets

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