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Urine Klotho Is Lower in Critically Ill Patients With Versus Without Acute Kidney Injury and Associates With Major Adverse Kidney Events.

ABSTRACT: Objective: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. Design:Single-center, prospective, case-control study. Setting:ICU in a tertiary medical center. Patients:54 AKI patients and 52 controls without AKI admitted to the ICU. Interventions:None. Measurements and Main Results: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. Conclusions: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.

SUBMITTER: Neyra JA

PROVIDER: S-EPMC7051168 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:OBJECTIVE:Guidelines recommend that encephalopathic critically ill children undergo continuous electroencephalographic (CEEG) monitoring for electrographic seizure (ES) identification and management. However, limited data exist on antiseizure medication (ASM) safety for ES treatment in critically ill children. METHODS:We performed a single-center prospective observational study of encephalopathic critically ill children undergoing CEEG. Clinical and EEG features and ASM utilization patterns were evaluated. We determined the incidence, types, and risk factors for adverse events associated with ASM administration. RESULTS:A total of 472 consecutive critically ill children undergoing CEEG were enrolled. ES occurred in 131 children (28%). Clinicians administered ASM to 108 children with ES (82%). ES terminated after the initial ASM in 38% of patients who received one ASM, after the second ASM in 35% of patients who received two ASMs, after the third ASM in 50% of patients who received three ASMs, and after the fourth ASM in 53% of patients who received four ASMs. Thirty patients (28%) received anesthetic infusions for ES management. Adverse events occurred in 18 patients (17%). Adverse effects were expected and resolved in all patients, and they were generally serious (in 15 patients) and definitely related (in 12 patients). Adverse events were rare in patients with acute symptomatic seizures requiring only one to two ASMs for treatment, but were more common in children with epilepsy, ictal-interictal continuum EEG patterns, or patients requiring more extensive ASM management. SIGNIFICANCE:ES ceased after one ASM in only 38% of critically ill children but ceased after two ASMs in 73% of critically ill children. Thus, ES management was often accomplished with readily available medications, but optimization of multistep ES management strategies might be beneficial. Adverse events were rare and manageable in children with acute symptomatic seizures requiring only one to two ASMs for treatment. Future studies are needed to determine whether management of acute symptomatic ES improves neurobehavioral outcomes.

Project description:AbstractResearch that focuses on transfers to and from the intensive care unit (ICU) could highlight important patients' safety issues. This study aims to describe healthcare workers' (HCWs) practices involved in patient transfers to or from the ICU.This cross-sectional study was conducted among HCWs during the Saudi Critical Care Society's annual International Conference, April 2017. Responses were assessed using Likert scales and frequencies. Bivariate analysis was used to evaluate the significance of different indicators.Overall, 312 HCWs participated in this study. Regarding transfer to ICUs, the most frequently reported complications were deterioration in respiratory status (51.4%), followed by deterioration in hemodynamic status (46.5%), and missing clinical information (35.5%). Regarding transfers from ICUs to the general ward, the most commonly reported complications were changes in respiratory status (55.6%), followed by incomplete clinical information (37.9%), and change in hemodynamic conditions (29%). The most-used models for communicating transfers were written documents in electronic health records (69.3%) and verbal communication (62.8%). One-fourth of the respondents were not aware of the Situation, Background, Assessment, Recommendation (SBAR) method of patients' handover. Pearson's test of correlation showed that the HCW's perceived satisfaction with their hospital transfer guidelines showed significant negative correlation with their reported transfer-related complications (r = -0.27, P < .010).Hemodynamic and respiratory status deterioration is representing significant adverse events among patients transferred to or from the ICU. Factors controlling the perceived satisfaction of HCWs involved in patients, transfer to and from the ICU need to be addressed, focusing on their compliance to the hospital-wide transfer and handover policies. Quality improvement initiatives could improve patient safety to transfer patients to and from the ICU and minimize the associated adverse events.

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Urine Klotho Is Lower in Critically Ill Patients With Versus Without Acute Kidney Injury and Associates With Major Adverse Kidney Events.

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