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INTRODUCTION: Acute kidney injury (AKI) is common in acute myocardial infarction (AMI) patients and has serious prognostic implications. The early identification of patients at risk of developing AKI at the emergency department (ED) can reduce its incidence. METHODS: Patients with ST-segment elevation myocardial infarction (STEMI) at the ED were included. Associated factors playing a role at ED presentation and during hospitalization were collected, and independent risk factors of developing AKI were assessed. RESULTS: Mean age among patients (n = 406, 69.7% male) was 62.5 ± 12.5 years. At ED admission, the mean glomerular filtration rate (GFR) was 70.5 ± 28.1 mL/min per 1.73 m(2), and 140 (34.5%) patients had a GFR <60 mL/min per 1.73 m(2). Eighty-three patients (20.4%) developed AKI: 47 (11.6%) with stage 1, 26 (6.4%) with stage 2 and 10 (2.5%) with stage 3. Mortality was 11.8% and was higher in patients with AKI (34.9% vs 5.9%, P < .0001). Univariate analysis disclosed age, reduced GFR at presentation, severe Killip class, heart rate and longer door-to-needle time as risk factors to develop AKI. Moreover, these patients received less [beta]-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in the ED. Multivariate analysis revealed that age, Killip class, heart rate, door-to-needle time, and [beta]-blocker non-use were independent factors associated with AKI. These factors provided the ED physician with good accuracy in identifying patients at high risk of developing AKI. CONCLUSION: Factors associated with AKI in STEMI patients allowed physicians to identify patients at high risk in the ED. Moreover, reduced door-to-needle time and [beta]-blocker use were associated with renal protection in AMI patients. [ABSTRACT FROM AUTHOR]

Introduction: Glomerular diseases, encompassing primary and secondary forms, pose significant morbidity and mortality risks. Despite their impact, little is known about critically ill patients with primary glomerulopathy admitted to the intensive care unit (ICU)., Methods: We conducted a case‒control study of patients with primary glomerulopathy using the Medical Information Mart for Intensive Care IV database. Demographic, clinical, and outcome data were collected. Logistic regression and mediation analysis were performed to identify predictors of hospital and long-term mortality., Results: Among 50,920 patients, 307 with primary glomerulopathy were included. Infectious and cardiovascular-related causes were the main reasons for ICU admission, with sepsis being diagnosed in more than half of the patients during their ICU stay. The hospital mortality rate was similar to that of the control group, with a long-term mortality rate of 29.0% three years post-ICU discharge. Reduced urine output and serum albumin were identified as independent predictors of hospital mortality, while serum albumin and the Charlson comorbidity index were significantly associated with long-term mortality. Notably, although acute kidney injury was frequent, it was not significantly associated with mortality. Additionally, reduced urine output mediates nearly 25% of the association between serum albumin and hospital mortality., Conclusion: Critically ill patients with primary glomerulopathy exhibit unique characteristics and outcomes. Although hospital mortality was comparable to that of the control group, long-term mortality remained high. The serum albumin concentration and Charlson Comorbidity Index score emerged as robust predictors of long-term mortality, highlighting the importance of comprehensive risk assessment in this population. The lack of an association between acute kidney injury and mortality suggests the need for further research to understand the complex interplay of factors influencing outcomes in this patient population., (© 2024. The Author(s).)

Introduction: Cognitive decline is prevalent in maintenance hemodialysis patients. The blood-brain barrier has been implicated in cognitive decline. In this prospective cohort study, we investigated the associations between endothelium-related biomarkers and steeper cognitive decline in this population., Methods: Cognitive function was assessed using the Portuguese-adapted Cambridge Cognitive Examination (CAMCOG) with items of the Mini-Mental State Examination (MMSE). Endothelium-related biomarkers included syndecan-1, ICAM-1, VCAM-1 and angiopoietin-2 (AGPT2). Patients were followed up for 4 years, and cognitive assessments were repeated. Multinomial regression analyses were performed to evaluate associations between biomarkers and cognitive decline., Results: A total of 216 patients completed the test battery at baseline. After 4 years, 102 patients had follow-up data. There was a significant decrease in cognitive function according to the CAMCOG and MMSE scores: a change of -0.39 (95% CI -0.27 to -0.51) and -0.51 (95% CI -0.27 to -0.76) standard deviation (SD) of the baseline scores. Additionally, executive function but not memory significantly decreased. Syndecan-1 level was independently associated with steeper cognitive decline; each increase in the SD of the syndecan-1 level was associated with a decrease in the CAMCOG of 0.20 (95% CI 0.07-0.33) SD from baseline. Syndecan-1 was associated with a steeper decline in MMSE score (β 0.54, 95% CI 0.28-0.81) and executive function (β 0.17, 95% CI 0.02-0.32). Syndecan-1 predicted severe cognitive impairment with an area under the curve for receiver operating characteristic curves of 0.75 (95% CI 0.64-0.83)., Conclusion: Our findings highlight the potential of syndecan-1, a biomarker of endothelium glycocalyx derangement, as a predictor of steeper cognitive decline in prevalent hemodialysis patients., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20-25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM)., Methods: Using the MIMIC-IV database, adult patients who received CKRT for more than 24 hours were included. Data on time-fixed and time-dependent variables were collected. Patients were categorized based on CKRT dose thresholds of 13 and 20 ml/kg/h., Results: Among the 1,329 patients, the 90-day mortality rate was 49.6%. The median age of the patients was 62 years (IQR: 52-72). Changes in CKRT dosing during treatment were frequent. Patients with a reduced delivered CKRT dose (<20 and < 13 ml/kg/h) generally exhibited low values during the initial days of CKRT, with an increase in the delivered CKRT dose. After adjusting only for baseline variables (traditional Cox regression model), patients receiving CKRT doses <13 ml/kg/h had significantly greater 90-day mortality (HR: 1.70, 95% CI 1.16-2.49) than those receiving CKRT doses ≥13 ml/kg/h. However, after adjusting for time-dependent variables, the CKRT dose was not significantly associated with mortality at either the 13 or 20 ml/kg/h threshold. Additionally, there were no significant associations between the delivered CKRT dose and 90-day mortality within the range of 5 to 40 ml/kg/h., Conclusion: This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association., (Copyright © 2024 by the Shock Society.)

Introduction: The current definition of acute kidney injury (AKI) includes increased serum creatinine (sCr) concentration and decreased urinary output (UO). Recent studies suggest that the standard UO threshold of 0.5 ml/kg/h may be suboptimal. This study aimed to develop and validate a novel UO-based AKI classification system that improves mortality prediction and patient stratification., Methods: Data were obtained from the MIMIC-IV and eICU databases. The development process included (1) evaluating UO as a continuous variable over 3-, 6-, 12-, and 24-h periods; (2) identifying 3 optimal UO cutoff points for each time window (stages 1, 2, and 3); (3) comparing sensitivity and specificity to develop a unified staging system; (4) assessing average versus persistent reduced UO hourly; (5) comparing the new UO-AKI system to the KDIGO UO-AKI system; (6) integrating sCr criteria with both systems and comparing them; and (7) validating the new classification with an independent cohort. In all these steps, the outcome was hospital mortality. Another analyzed outcome was 90-day mortality. The analyses included ROC curve analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and logistic and Cox regression analyses., Results: From the MIMIC-IV database, 35,845 patients were included in the development cohort. After comparing the sensitivity and specificity of 12 different lowest UO thresholds across four time frames, 3 cutoff points were selected to compose the proposed UO-AKI classification: stage 1 (0.2-0.3 mL/kg/h), stage 2 (0.1-0.2 mL/kg/h), and stage 3 (< 0.1 mL/kg/h) over 6 h. The proposed classification had better discrimination when the average was used than when the persistent method was used. The adjusted odds ratio demonstrated a significant stepwise increase in hospital mortality with advancing UO-AKI stage. The proposed classification combined or not with the sCr criterion outperformed the KDIGO criteria in terms of predictive accuracy-AUC-ROC 0.75 (0.74-0.76) vs. 0.69 (0.68-0.70); NRI: 25.4% (95% CI: 23.3-27.6); and IDI: 4.0% (95% CI: 3.6-4.5). External validation with the eICU database confirmed the superior performance of the new classification system., Conclusion: The proposed UO-AKI classification enhances mortality prediction and patient stratification in critically ill patients, offering a more accurate and practical approach than the current KDIGO criteria., (© 2024. The Author(s).)

Introduction: Femoral fractures in elderly individuals present significant health challenges, often leading to increased morbidity and mortality. Acute kidney injury (AKI) during hospitalization further complicates outcomes, yet the interaction between AKI severity and comorbidities, as quantified by the Charlson Comorbidity Index (CCI), remains poorly understood in this population. This study aimed to assess the associations between AKI severity and the CCI and between AKI severity and one-year mortality postfemoral fracture in elderly patients., Methodology: This study utilized data from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database and focused on elderly patients (> 65 years) admitted with hip fractures. Patients were categorized based on AKI stage according to the KDIGO criteria and CCI scores. The primary outcome assessed was all-cause mortality one year after hospital discharge. The statistical analyses included logistic regression, Cox proportional hazards regression and moderation analysis with the Johnson-Neyman technique to evaluate associations between AKI and long-term mortality and between the CCI and long-term mortality., Results: The analysis included 1,955 patients and revealed that severe AKI (stages 2 and 3) was independently associated with increased one-year mortality. Notably, the CCI moderated these associations significantly. A lower CCI score was significantly correlated with greater mortality in patients with severe AKI. The impact of severe AKI was greater for those with a CCI as low as 3, more than doubling the observed one-year mortality rate. In contrast, higher CCI scores (≥8) did not significantly impact mortality. Sensitivity analyses supported these findings, underscoring the robustness of the observed associations., Conclusion: This study elucidates the complex interplay between AKI severity and comorbidities and long-term mortality in elderly hip fracture patients. These findings underscore the importance of considering both AKI severity and comorbidity burden in prognostic assessments and intervention strategies for this vulnerable population. Targeted interventions tailored to individual risk profiles may help mitigate the impact of AKI on mortality outcomes, ultimately improving patient care and outcomes. Further research is warranted to explore the underlying mechanisms involved and refine risk stratification approaches in this population., (© 2024. The Author(s).)

Acute kidney injury (AKI) is a common condition in hospitalized patients who often requires kidney support therapy (KST). However, predicting the need for KST in critically ill patients remains challenging. This study aimed to analyze endothelium-related biomarkers as predictors of KST need in critically ill patients with stage 2 AKI. A prospective observational study was conducted on 127 adult ICU patients with stage 2 AKI by serum creatinine only. Endothelium-related biomarkers, including vascular cell adhesion protein-1 (VCAM-1), angiopoietin (AGPT) 1 and 2, and syndecan-1, were measured. Clinical parameters and outcomes were recorded. Logistic regression models, receiver operating characteristic (ROC) curves, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used for analysis. Among the patients, 22 (17.2%) required KST within 72 h. AGPT2 and syndecan-1 levels were significantly greater in patients who progressed to the KST. Multivariate analysis revealed that AGPT2 and syndecan-1 were independently associated with the need for KST. The area under the ROC curve (AUC-ROC) for AGPT2 and syndecan-1 performed better than did the constructed clinical model in predicting KST. The combination of AGPT2 and syndecan-1 improved the discrimination capacity of predicting KST beyond that of the clinical model alone. Additionally, this combination improved the classification accuracy of the NRI and IDI. AGPT2 and syndecan-1 demonstrated predictive value for the need for KST in critically ill patients with stage 2 AKI. The combination of AGPT2 and syndecan-1 alone enhanced the predictive capacity of predicting KST beyond clinical variables alone. These findings may contribute to the early identification of patients who will benefit from KST and aid in the management of AKI in critically ill patients., (© 2024. The Author(s).)

Introduction: Up to 70% of intermittent hemodialysis (IHD) sessions in critically ill patients are complicated by hemodynamic instability. Although several clinical characteristics have been associated with hemodynamic instability during IHD, the discriminatory capacity of predicting such events during IHD sessions is less defined. In the present study, we aimed to analyse endothelium-related biomarkers collected before IHD sessions and their capacity to predict hemodynamic instability related to IHD in critically ill patients., Methods: In this prospective observational study, we enrolled adult critically ill patients with acute kidney injury who required fluid removal with IHD. We screened each included patient daily for IHD sessions. Thirty minutes before each IHD session, each patient had a 5-mL blood collection for measurement of endothelial biomarkers-vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-1 and -2 (AGPT1 and AGPT2) and syndecan-1. Hemodynamic instability during IHD was the main outcome. Analyses were adjusted for variables already known to be associated with hemodynamic instability during IHD., Results: Plasma syndecan-1 was the only endothelium-related biomarker independently associated with hemodynamic instability. The accuracy of syndecan-1 for predicting hemodynamic instability during IHD was moderate [area under the receiver operating characteristic curve 0.78 (95% confidence interval 0.68-0.89)]. The addition of syndecan-1 improved the discrimination capacity of a clinical model from 0.67 to 0.82 ( P  < .001) and improved risk prediction, as measured by net reclassification improvement., Conclusion: Syndecan-1 is associated with hemodynamic instability during IHD in critically ill patients. It may be useful to identify patients who are at increased risk for such events and suggests that endothelial glycocalyx derangement is involved in the pathophysiology of IHD-related hemodynamic instability., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objective: To investigate the prediction ability of vascular injury biomarkers for haemodialysis requirement in patients with severe leptospirosis., Methods: Prospective study with severe leptospirosis patients hospitalised in Fortaleza, Brazil. Blood samples were collected hospital admission to quantify vascular injury biomarkers: syndecan-1, ICAM-1, VCAM-1, angiopoietin-2 and FGF-23. Two groups were evaluated according to haemodialysis requirement during hospital stay., Results: Twenty-seven patients were included, with a mean age of 39 ± 18 years. 88.9% were males. 53.8% needed haemodialysis and presented higher levels on hospital admission of syndecan-1 (572 [300-811] vs. 263 [106-421] ng/ml; p = 0.03), angiopoietin-2 (1.52 [0.72-2.72] vs. 0.63 [0.4-1.38] ng/ml; p = 0.01), and FGF-23 (291 [56-2031] vs. 10 [10-806] pg/ml; p = 0.021). Syndecan-1 showed significant correlation with creatinine (r = 0.546; p = 0.05) and total bilirubin levels (r = 0.534; p = 0.013) on hospital admission. Angiopoietin-2 showed significant correlation with creatinine levels (r = 0.513; p = 0.009) on hospital admission and with number of haemodialysis sessions (r = 0.406; p = 0.049). No significant correlation was found with FGF-23. Regarding prognostic performance, combined syndecan-1 and angiopoietin-2 levels had a better ability to predict haemodialysis need in patients with severe leptospirosis (AUC-ROC = 0.744 [95% CI: 0.545-0.943] p = 0.035)., Conclusion: Syndecan-1 and angiopoietin-2 were associated with haemodialysis need in patients with severe leptospirosis and may be useful to improve therapeutic approach and reduce mortality., (© 2022 John Wiley & Sons Ltd.)

Cardiac remodeling is the initial process in heart failure development. The aim of this study is to evaluate the association between endothelium-related biomarkers and cardiac remodeling in hemodialysis (HD) patients and how the presence of high blood pressure and diabetes mellitus modulates these associations. This was a cross-sectional study with adult HD and normal left ventricular (LV) ejection fraction-LVEF-patients. The authors correlated several endothelium-related biomarkers with echocardiographic indices-LV mass index (LVMi), LVEF, global longitudinal strain, mitral E/e', and aortic root diameter. Seventy-one patients were included, with 37 women (52.1%) and mean age of 54.3 ± 16.8 years. Angiopoietin-2 (AGPT2) was inversely correlated with global longitudinal strain (r = -.374, p = .001) and directly with E/e' (r = .265, p = .025). After adjustment, only AGPT2 was significantly associated with global longitudinal strain. blood pressure and diabetes mellitus were independent moderators for the AGPT2 and global longitudinal strain association. The conditional association was significant only when the mean pre-HD blood pressure was above 97.5 mmHg or in diabetes mellitus patients. Finally, there was an interaction between diabetes mellitus and blood pressure when moderating the conditional effect of AGPT2 on global longitudinal strain. While in non-diabetic patients, the association between AGPT2 with global longitudinal strain was significant only with pre-HD blood pressure levels as high as 110 mmHg, in diabetic patients, this association was significant with pre-HD blood pressure as low as 90 mmHg. Higher levels of AGPT2 were associated with worse cardiac function as determined by lower global longitudinal strain values. This association was moderated by blood pressure and diabetes mellitus, suggesting that the effects of AGPT2 on cardiac remodeling is dependent of such circumstances., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Acute kidney injury (AKI) is characterized by a sudden decrease in kidney function. Children with congenital heart disease are a special group at risk of developing AKI. We performed a systematic review of the literature to search for studies reporting the usefulness of novel urine, serum, and plasma biomarkers in the diagnosis and progression of AKI and their association with clinical outcomes in children undergoing pediatric cardiac surgery. In thirty studies, we analyzed the capacity to predict AKI and poor outcomes of five biomarkers: Cystatin C, Neutrophil gelatinase-associated lipocalin, Interleukin-18, Kidney injury molecule-1, and Liver fatty acid-binding protein. In conclusion, we suggest the need for further meta-analyses with the availability of additional studies., (© 2021. IPNA.)

Objective: Liver transplant (LT) is a definitive therapeutic option for patients with chronic liver disease. However, acute kidney injury after LT (post-LT AKI) is a frequent complication that may lead to graft dysfunction and decrease life expectancy. Delay in AKI detection by traditional biomarkers boosted research with new biomarkers for post-LT AKI as neutrophil gelatinase-associated lipocalin (NGAL) and syndecan-1. We aim to evaluate associations of intraoperative systemic NGAL and syndecan-1 levels with post-LT AKI., Methods: This is a prospective study conducted in 46 patients selected for LT. Patients were evaluated preoperatively and blood samples were collected intraoperatively: T1 (after induction of anesthesia), T2 (anhepatic phase) and T3 (2 h after reperfusion of the graft)., Results: The mean age was 54 ± 12 years and 60% were male. Post-LT AKI was observed in 24 (52%) patients of which 12% needed dialysis. Serum NGAL and syndecan-1 increased along surgical phases. Mostly, increment values of serum NGAL of T2 to T3 and syndecan-1 at T3 were importantly associated with post-LT AKI. Into a multivariate model with model for end-stage liver disease score, age, gender, warm ischemia, cold ischemia and surgery time, syndecan-1 levels at T3 remains capable to predict post-LT AKI. Serum NGAL had significance only with increment values calculated by the ratio of 'T3/T2'. Finally, serum syndecan-1 at T3 had a better diagnostic performance in receiver operating characteristic curve analysis., Conclusion: Serum syndecan-1 levels in 2 h after reperfusion were most useful in early post-LT AKI diagnosis and may be used to construct new risk groups in this context., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Patients with chronic kidney disease (CKD) may present impaired functional capacity due to peripheral muscle involvement. Oxidative stress and inflammation are probably involved in this pathophysiology. This study aimed to evaluate the association between functional capacity and biomarkers of oxidative stress as well as biomarkers of inflammation in patients under chronic hemodialysis therapy., Method: Cross-sectional study including 41 patients from a single hemodialysis center. Functional capacity was assessed through the 6-min walk test (6MWT). The assessed blood biomarkers were: malondialdehyde (MDA) (oxidative stress, TBARS method) and angiopoietin-2 (Ang-2) (inflammation, ELISA). The influence of gender on impairment of functional capacity was further explored., Results: There was an inversely proportional correlation between the 6MWD and MDA (r = -,322 and p = 0.040) and Ang-2 (r = -, 376 and p = 0.016) values. 6MWD was 370.9 ± 101.2 m and 391.4 ± 108.2 m in women and men, respectively (p < 0.001), which means 29.3% and 34.3% reduction of the expected values for healthy individuals from the same age range., Conclusion: Patients with CKD under hemodialysis, regardless of gender, presented impaired performance in 6MWT and this impairment was associated with oxidative stress and inflammation., Competing Interests: Declaration of competing interest The authors declare that they participated in the conception, analysis of results and effectively contributed to the realization of the article: " Correlation between functional capacity and biomarkers of oxidative stress and inflammation in stage 5 patients with chronic kidney disease under hemodialysis therapy”. They disclose the responsibility for its content, which has not omitted any links or financing agreements between the authors and companies that may have an interest in the publication of this article. We declare that the article cited above is original and that it has no conflict of interest with the topic addressed in the article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Haemodialysis (HD) patients have a high prevalence of cardiovascular disease risk factors as well as cognitive impairment. The objective of the present study was to evaluate the interrelationship between cognitive impairment, endothelium-related biomarkers and cardiovascular/non-cardiovascular mortality., Methods: A total of 216 outpatients were recruited from three centres in a dialysis network in Brazil between June 2016 and June 2019. Sociodemographic and clinical data were obtained by applying a patient questionnaire, reviewing medical records data and conducting patient interviews. Cognitive function was assessed using the Cambridge Cognitive Examination. Plasma endothelium-related biomarkers [syndecan-1, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1) and angiopoietin-2 (AGPT2)] were measured. Patients were followed for 30 months. Cox proportional hazards regression models were used to assess the associations of the cognitive function scores and each endothelium-related biomarker with cardiovascular/non-cardiovascular mortality., Results: Cognitive function was associated with cardiovascular mortality {each standard deviation [SD] better cognitive score was associated with a 69% lower risk for cardiovascular mortality [hazard ratio (HR) 0.31 [95% confidence interval (CI) 0.17-0.58]} but not with non-cardiovascular mortality. Moreover, cognitive function was also correlated with all endothelial-related biomarkers, except VCAM-1. ICAM-1, AGPT2 and syndecan-1 were also associated with cardiovascular mortality. The association between cognitive function and cardiovascular mortality remained significant with no HR value attenuation [fully adjusted HR 0.32 (95% CI 0.16-0.59)] after individually including each endothelial-related biomarker in the Cox model., Conclusions: In conclusion, cognitive impairment was associated with several endothelium-related biomarkers. Moreover, cognitive impairment was associated with cardiovascular mortality but not with non-cardiovascular mortality, and the association between cognitive impairment and cardiovascular mortality in HD patients was not explained by any of the endothelial-related biomarkers., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Although vancomycin nephrotoxicity is recognizable, critically ill patients have other potential reasons for acute kidney injury (AKI) and determining its attributable nephrotoxic risk in this population can be cumbersome., Objectives: To determine the risk of AKI attributable to vancomycin, controlling for baseline and time-dependent confounders., Methods: Time-fixed and daily time-varying variables were extracted from a large public database. The exposures analysed were: (i) IV vancomycin; (ii) serum trough level greater than 15 and 20 mg/L; and (iii) concomitant exposure to vancomycin and piperacillin/tazobactam or other antipseudomonal β-lactams. Censoring and exposure inverse probability of treatment weighting were calculated. Marginal structural models were plotted to evaluate AKI, severe AKI (stage 2/3) and need of renal replacement therapy (RRT)., Results: A total of 26 865 patients were included; 19.7% received vancomycin during ICU stay. After adjusting for fixed and time-variable confounders, vancomycin exposure was associated with AKI (HR = 1.24, 95% CI = 1.09-1.38), but not with severe AKI or need of RRT (HR = 1.05, 95% CI = 0.91-1.23 and HR = 0.97, 95% CI = 0.74-1.29, respectively). A serum trough level greater than 20 mg/L was associated with AKI (HR = 1.90, 95% CI = 1.52-2.30) and severe AKI (HR = 1.69, 95% CI = 1.31-2.19), but showed no statistically significant association with need of RRT (HR = 1.48, 95% CI = 0.92-2.56). The vancomycin + piperacillin/tazobactam combination was not associated with a greater risk than vancomycin alone., Conclusions: The attributable nephrotoxicity of vancomycin in critically ill patients is significantly lower than previously suggested and severe AKI is related to vancomycin only when trough serum levels are greater than 20 mg/L., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The impact of the use of loop diuretics to prevent cumulative fluid balance in non-oliguric patients is uncertain. This is a retrospective study to estimate the association of time-averaging loop diuretic exposure in a large population of non-cardiac, critically ill patients with a positive fluid balance (> 5% of body weight). The exposure was loop diuretic and the main outcomes were 28-day mortality, severe acute kidney injury and successful mechanical ventilation weaning. Time-fixed and daily time-varying variables were evaluated with a marginal structural Cox model, adjusting bias for time-varying exposure and the presence of time-dependent confounders. A total of 14,896 patients were included. Patients receiving loop diuretics had better survival (unadjusted hazard ratio 0.56, 95%CI 0.39-0.81 and baseline variables adjusted hazard ratio 0.53, 95%CI 0.45-0.62); after full adjusting, loop diuretics had no association with 28-day mortality (full adjusted hazard ratio 1.07, 95%CI 0.74-1.54) or with reducing severe acute kidney injury occurrence during intensive care unit stay - hazard ratio 1.05 (95%CI 0.78-1.42). However, we identified an association with prolonged mechanical ventilation (hazard ratio 1.59, 95%CI 1.35-1.89). The main results were consistent in the sub-group analysis for sepsis, oliguria and the study period (2002-2007 vs. 2008-2012). Also, equivalent doses of up to 80 mg per day of furosemide had no significant association with mortality. After adjusting for time-varying variables, the time average of loop diuretic exposure in non-cardiac, critically ill patients has no association with overall mortality or severe acute kidney injury; however, prolonged mechanical ventilation is a concern., (© 2020 Association of Anaesthetists.)

Background: Assess the respiratory-related parameters associated with subsequent severe acute kidney injury in mechanically ventilated patients with acute respiratory distress syndrome (ARDS)., Methods: Retrospective cohort, analyzing a large public database-Multiparameter Intelligent Monitoring in Intensive Care-III. Adult patients with at least 48 h of mechanical ventilation (MV), under volume controlled ventilation and an oxygenation index less than 300 mmHg were included., Results: A total of 1,142 patients had complete data and were included in the final analyses. According to a causal directed acyclic graph (DAG) that included respiratory system compliance (C rs ), tidal volume (Vt), driving pressure (ΔP), plateau pressure (P Plat ), PEEP, PaO 2 and PaCO 2 as possible exposures related to severe AKI, only C rs and PEEP levels had significant causal association with severe acute kidney injury (AKI) (OR 0.90, 95% CI: 0.84-0.94 for each 5-mL/cmH 2 O reduction in C rs ; OR, 1.05 95% CI: 1.03-1.10 for each 1-cmH 2 O increase of PEEP). Using mediation analysis, we examined whether any mechanical ventilation, blood gas or hemodynamic parameters could explain the effects of C sr on AKI. Only PEEP mediated the significant but small effect (less than 5%) of C sr on severe AKI. The effects of PEEP, in turn, were not mediated by any other evaluated parameter. Several sensitivity analyses with (I) need of renal replacement therapy (RRT) as an alternative outcome and (II) only patients with Vt <8 mL/kg, confirmed our main findings. In trying to validate our DAG assumptions, we confirmed that only ΔP was associated with mortality but not with severe AKI., Conclusions: C rs and PEEP are the only respiratory-related variables with a direct causal association in severe AKI. No mechanical ventilator or blood gas parameter mediated the effects of C rs . Approaches reducing Vt and/or ΔP in ARDS can have limited effect on renal protection., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Annals of Translational Medicine. All rights reserved.)

Background: Fibroblast growth factor 23 (FGF23) and endothelium-related biomarkers have been related to AKI in critically-ill patients. Also, FGF23 is associated with endothelial dysfunction. In this study, we investigated if elevated FGF23 association with severe AKI is mediated by several endothelial/glycocalyx-related biomarkers., Methods: Prospective cohort study with critically-ill patients. Blood samples were collected within the first 24 h after ICU admission. Severe AKI (defined according to KDIGO stage 2/3) was the analyzed outcome., Results: 265 patients were enrolled and 82 (30.9%) developed severe AKI-defined according to KDIGO stage 2/3. Blood samples to biomarkers measurement were collected within the first 24 h after ICU admission. After adjustment for several variables, FGF23, vascular cell adhesion protein 1 (VCAM-1), angiopoietin 2 (AGPT2), syndecan-1 and intercellular adhesion molecule-1 (ICAM-1) were associated with severe AKI. The individual indirect effects of VCAM-1, AGPT2 and syndecan-1 explained 23%, 31%, and 32% of the total observed effect of FGF23 on severe AKI, respectively. ICAM-1 showed no statistically significant mediation. When all three endothelium-related biomarkers were included in a directed acyclic graph (DAG), the Bayesian network learning suggested the following causal association pathway FGF-23 → syndecan-1 → VCAM-1 → AGPT2 → severe AKI., Conclusions: The association between FGF23 and AKI are mediated by endothelium-related biomarkers, mainly VCAM-1, AGPT2 and syndecan-1. Moreover, the statistical models show that syndecan-1, a biomarker of endothelial glycocalyx dysfunction, seems to be the initial mediator between FGF23 and severe AKI.

Background and Objective: Angiopoietin-2 (AGPT2) has been proposed as a key mediator of organ dysfunction, mainly in acute respiratory distress syndrome (ARDS). It has also been associated with acute kidney injury (AKI). We aimed to investigate the role of AGPT2 in patients with and without ARDS., Methods: In a cohort study with critically ill patients, AGPT1 and AGPT2 were assayed in plasma collected within the first 24 h after admission to intensive care unit (ICU). Severe AKI and the need for dialysis were outcome measures from comparative analysis with clinical characteristics useful for AKI risk stratification., Results: Among 283 patients (50.2% males), 109 (38.5%) had ARDS. AGPT2 levels at admission were higher in patients with ARDS. Although overall AGPT2 and AGPT2/AGPT1 levels were associated with severe AKI, this association was not significant in patients without ARDS; however, it remained strongly significant in ARDS patients. In patients without ARDS, AGPT2 showed only a weak discriminatory capacity to predict severe AKI (area under the curve (AUC): 0.64 vs 0.81 in the ARDS group). The continuous net reclassification improvement (NRI) in the ARDS group resulting from AGPT2 inclusion was 64.1% (P < 0.001) and the integrated discrimination improvement (IDI) index was 0.057 (P = 0.003). There was no significant difference in NRI in the no-ARDS group., Conclusion: AGPT2 and AGPT2/AGPT1 ratio are associated with severe AKI and there was only a need of renal replacement therapy (RRT) in patients with or at risk of ARDS, not in other critically ill patients. Adding AGPT2 to a clinical model resulted in a significant improvement in the capacity to predict severe AKI specifically in ARDS patients., (© 2019 Asian Pacific Society of Respirology.)

Introduction: Glomerulopathy is a group of diseases that affect mainly young adults between the ages of 20 and 40 years. Recently, it has been demonstrated that syndecan-1, a biomarker of endothelial glycocalyx damage, is increased in nephrotic patients with near-normal renal function and it is important to endothelial dysfunction in these patients. Angiopoietin-2 (AGPT2) is an endothelial growth factor that promotes cell derangement. Here we evaluated AGPT2 levels in patients with nephrotic syndrome, near-normal renal function and the possible interaction of AGPT2 with endothelial glycocalyx derangement., Methods: This was a cross-sectional study performed from January through November 2017. Adult patients (age > 18 years) with nephrotic syndrome and without immunosuppression were included. Blood samples were drawn after a 12 h fast for later measurement of syndecan-1 and AGPT2. Mediation analyses were performed to assess the hypothesized associations of nephrotic syndrome features and AGPT2 with syndecan-1., Results: We included 65 patients, 37 (56.9%) of them female, with primary glomerular disease. Syndecan-1 in nephrotic patients was higher than in control individuals (102.8 ± 36.2 vs. 28.2 ± 9.8 ng/mL, p < 0.001). Correlation of syndecan-1 with the main features of nephrotic syndrome after adjustment for age and estmmated glomerular filtration rate (eGFR) demonstrated that syndecan-1 was significantly associated with 24-h urinary protein excretion, total cholesterol, LDL (low density lipoprotein)-cholesterol, HDL (high-density lipoprotein)-cholesterol, and triglycerides. Angiopoietin-2 was independently associated with serum albumin, 24 h urinary protein excretion, total cholesterol, and LDL-cholesterol, in addition to being strongly associated with syndecan-1 (0.461, p < 0.001). The results of the mediation analyses showed that the direct association between LDL-cholesterol and syndecan-1 was no longer significant after AGPT-2 was included in the mediation analysis. AGPT2 explained 56% of the total observed association between LDL-cholesterol and syndecan-1., Conclusion: The association between LDL-cholesterol and glycocalyx derangement in nephrotic patients is possibly mediated by AGPT2.

Objective: To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis., Methods: Prospective study with 50 hospitalised VL patients. AKI biomarkers, that is, serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL, uNGAL, respectively), urinary kidney injury molecule-1 (uKIM-1) and urinary monocyte chemotactic protein-1 (uMCP-1), were quantified by immunoassay (ELISA). Also, interferon-gamma (INF-y) and C-reactive protein (CRP) were evaluated as inflammatory biomarkers possibly related to VL severity., Results: VL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia, haematologic and hepatic disorders. AKI was found in 46%, and one death (2%) occurred. The AKI group had significant longer hospital stay, lower levels of IFN-y and higher levels of CRP, more clinical renal abnormalities and higher levels of sNGAL, uNGAL, uKIM-1 and uMCP-1. Overall, sNGAL, uKIM-1 and uMCP-1 showed correlations with important clinical renal abnormalities, such as proteinuria, albuminuria, serum creatinine and glomerular filtration rate using adjusted correlations with CRP and IFN-y. Only sNGAL showed an early association with AKI development (OR = 2.78, 95% CI = 1.429-5.428, per each increase of 50 ng/ml), even after adjusting for clinical signals of VL severity and for immune biomarkers. Moreover, sNGAL showed a better performance in predicting AKI development (AUC-ROC = 0.81, 95% CI = 0.69-0.93; cut-off = 154 ng/ml, sensitivity = 82.6%, specificity = 74.1%, P < 0.001)., Conclusions: Visceral leishmaniasis-associated nephropathy showed important proximal tubular injury and glomerular inflammation. Serum NGAL showed an early association with VL-associated nephropathy and may be used to improve clinical management strategies and decrease morbimortality in VL patients., (© 2018 John Wiley & Sons Ltd.)

Introduction: Acute kidney injury (AKI) is a common occurrence after pediatric cardiac surgery. Plasma syndecan-1 is a biomarker of endothelial glycocalyx damage and it is associated with AKI. Syndecan-1 is also expressed in renal tubular cells but there is no study evaluating urinary syndecan-1 in predicting AKI., Methods: Prospective cohort study with 86 patients ≤18 years submitted to cardiac surgery at one reference institution. Postoperative urinary syndecan-1 was collected within the first 2 h after cardiac surgery. Severe AKI - defined according to KDIGO as stage 2 or 3 - doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization was the main outcome. Analyses were adjusted for clinical cofounders., Results: Postoperative urinary syndecan-1 levels were higher in patients with severe AKI and even after adjustment for several clinical variables; the fourth quartile was significantly associated with severe AKI. The AUC-ROC for postoperative urinary syndecan-1 showed good discriminatory capacity (AUC-ROC = 0.793). The addition of urinary syndecan-1 improved the discrimination capacity of a clinical model (0.78 to 0.84). It also improved risk prediction, as measured by net reclassification improvement (NRI)., Conclusion: Urinary syndecan-1 predicts severe AKI after pediatric cardiac surgery. Moreover, it appears to add capacity to predict severe AKI into a clinical model., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: A recent prognostic model, predicting 60-day case fatality in critically ill patients requiring renal replacement therapy (RRT), has been developed (Acute Renal Failure Trial Network [ATN] study). Because many prognostic models are suggested in literature, but just a few have found its way into clinical practice, we aimed to externally validate this prediction model in an independent cohort., Methods: A total of 1,053 critically ill patients requiring RRT from the MIMIC-III database were analyzed. The models' discrimination was evaluated using c-statistics. Calibration was evaluated by Hosmer-Lemeshow (H-L) test and GiViTi calibration belt., Results: In a case-mix population, including patients with normal or altered serum creatinine (sCr) at intensive care unit admission, discrimination was moderate, with a c-statistic of 0.71 in the nonintegerized risk model. In patients with altered baseline sCr, better discrimination was achieved with the integer risk model (0.76, 95% confidence interval, 0.71-0.81). As for the calibration, although the H-L test was good only in patients with normal/slightly altered sCr at admission, the calibration belt disclosed no significant deviations from the bisector line for any of the models in patients, regardless of admission sCr. Of note, a refitted model had a c-statistics of 0.85, similar to the derivation cohort., Conclusions: The ATN prognostic model can be useful in a broad cohort of critically ill patients. Although it showed only moderate discrimination capacity when patients with elevated admission sCr were included, using a refitted model improved it, illustrating the need for continuous external validation and updating of prognostic models over time before their implementation in clinical practice.

Introduction: Common variable immunodeficiency (CVID) comprises a heterogeneous group of disorders characterized by impaired antibody production. Kidney involvement in CVID is described in isolated and sporadic case reports. The objective of this study was to study the renal function pattern in CVID patients through glomerular and tubular function tests., Methods: Study of 12 patients with CVID diagnosis and 12 healthy control individuals. Glomerular filtration rate (GFR), fractional excretion of sodium (FE Na + ) and potassium (FE K + ), urinary concentration, and acidification capacity were measured. In addition, microalbuminuria and urinary monocyte chemoattractant protein-1 (MCP-1) were evaluated as markers of selectivity of the glomerular barrier and inflammation, respectively., Results: In relation to glomerular markers, all CVID patients had normal GFR (>90 mL/min/1.73 m 2 ), and microalbuminuria and urinary MCP-1 levels were also similar to those of controls. Interestingly, CVID patients had reduced urinary concentration capacity, as demonstrated by lower U / P Osm ratio, when compared to controls. Also, while all control subjects achieved a urinary pH less than 5.3, no CVID patients showed a decrease in urinary pH to such levels in response to acid loading with CaCl 2 , characterizing impaired urinary acidification capacity., Conclusion: Patients showed a trend towards an elevated prevalence of tubular dysfunction, mainly related to urinary acidification and concentration capacities.

Introduction: Hemodialysis (HD) patients have altered pulmonary function and this is associated with impaired endothelial function and cardiovascular events. Respiratory muscle training (RMT) has the potential to improve cardiovascular outcomes in patients undergoing maintenance HD. Here, we evaluated the effects of RMT on endothelium/glycocalyx, oxidative stress biomarkers and pulmonary function test in HD patients., Methods: This is a randomized controlled clinical trial including 41 patients undergoing thrice-weekly maintenance HD. Patients were randomly assigned at a 2:1 ratio to receive or not RMT during HD sessions for 8 weeks. Main outcomes were changes in levels of the biomarkers related to endothelium activation (vascular cell adhesion molecule 1, VCAM-1, and intercellular adhesion molecule 1, ICAM-1), glycocalyx derangement (syndecan-1), aberrant angiogenesis (angiopoietin-2) and oxidative stress (malondialdehyde) compared to baseline. Also, maximal inspiratory/expiratory pressure (MIP, MEP), Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) were evaluated. Other outcomes included changes in functional capacity and pulmonary function test. We also performed a post-hoc analysis of plasma endothelin-1 levels., Results: Of 56 randomly assigned patients, 41 were included in the primary final analyses. RMT increased all pulmonary function parameters evaluated and significantly reduced plasma syndecan-1 levels at 8 weeks compared to placebo (between-group difference: -84.5; 95% CI, -148.1 to -20.9). Also, there was a reduction in plasma levels of angiopoietin-2 (between-group difference: -0.48; 95% CI, -1.03 to -0.097). Moreover, there was a significant reduction in mean blood pressure at rest (between-group difference: -12.2; 95%CI, -17.8 to -6.6) associated with a reduction in endothelin-1 levels (between-group difference: -0.164; 95% CI, -0.293 to -0.034). There was no difference regarding biomarkers of endothelial activation or oxidative stress., Conclusion: A short-term RMT program ameliorate FVC, FEV1 and reduces syndecan-1 and angiopoietin-2 biomarker levels. Finally, better blood pressure control was attained during training and it was associated with a reduction in endothelin-1 levels., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Although significant advances have been achieved in acute kidney injury (AKI) research following its classification, potential pitfalls can be identified in clinical practice. The nonsteady-state (kinetic) estimated glomerular filtration rate (KeGFR) could add clinical and prognostic information in critically ill patients beyond the current AKI classification system., Methods: This was a retrospective analysis using data from the Multiparameter Intelligent Monitoring in Intensive Care II project. The KeGFR was calculated during the first 7 days of intensive care unit (ICU) stay in 13,284 patients and was correlated with outcomes., Results: In general, there was not a good agreement between AKI severity and the worst achieved KeGFR. The stepwise reduction in the worst achieved KeGFR conferred an incremental risk of death, rising from 7.0% (KeGFR > 70 ml/min/1.73 m 2 ) to 27.8% (KeGFR < 30 ml/min/1.73 m 2 ). This stepwise increment in mortality remained in each AKI severity stage. For example, patients with AKI stage 3 who maintained KeGFR had a mortality rate of 16.5%, close to those patients with KeGFR < 30 ml/min/1.73 m 2 but no AKI; otherwise, mortality increased to 40% when both AKI stage 3 and KeGFR < 30 ml/min/1.73 m 2 were present. In relation to another outcome-renal replacement therapy (RRT)-patients with the worst achieved KeGFR < 30 ml/min/1.73 m 2 and KDIGO stage 1/2 had a rate of RRT of less than 10%. However, this rate was 44% when both AKI stage 3 and a worst KeGFR < 30 ml/min/1.73 m 2 were observed. This interaction between AKI and KeGFR was also present when looking at long-term survival., Conclusion: Both the AKI classification system and KeGFR are complementary to each other. Assessing both AKI stage and KeGFR can help to identify patients at different risk levels in clinical practice.

Widespread use of combined antiretroviral therapy (cART) increased HIV patients' life expectancy, however, favored the development of kidney and cardiovascular diseases. The aim of this study was to investigate endothelial glycocalyx (eGC) damage and its association with renal function in HIV patients receiving cART. This is a cross-sectional study with HIV-infected patients with no renal and cardiovascular disease, recruited in public health centers in Brazil. Clinical and laboratory parameters of HIV patients were compared according to cART use and with a healthy control group. Blood ICAM-1 and syndecan-1 levels were quantified by ELISA kit. Estimated glomerular filtration rate (eGFR) was evaluated. A total of 69 HIV patients were included, with mean age of 33.4 ± 8.9 years, and 77.3% were male. Serum urea, creatinine, and eGFR were similar in all groups. No HIV patient had decreased GFR <60 ml/min. All HIV patients had higher systemic syndecan-1 compared with healthy controls (71.8 ± 25.4 ng/ml vs. 36.5 ± 14.3 ng/ml, p < .001). Syndecan-1 showed a significant positive correlation with serum creatinine (r = 0.437, p = .001), serum urea levels (r = 0.352, p = .006), and a negative correlation with eGFR (r = -0.315, p = .015) in HIV patients. Syndecan-1 remained independently associated with serum creatinine and reduced GFR even after we forced variables related with HIV infection status, tenofovir use, treatment time, dyslipidemia, and others in a multivariate analysis. HIV patients using cART with no clinical renal and cardiovascular disease presented eGC damage and it is associated with clinical markers of kidney dysfunction. Syndecan-1 may be a useful early biomarker to monitoring renal dysfunction in HIV patients in chronic use of cART. Further research is needed to evaluate this applicability.

Resilience and religiosity have received attention as an important process in the experience and management of chronic comorbidities; however, there is no study evaluating resilience in hemodialysis patients and its association with other psychological dimensions or with treatment adherence. This observational prospective study assessed resilience (25 item Wagnild and Young Resilience Scale), religiosity under three dimensions (organizational, non-organizational and intrinsic) using DUREL scale, depressive symptoms (Patient Health Questionnaire-9) and health-related quality of life (Short Form-36 questionnaire). The main outcomes were medication adherence using the Morisky Medication Adherence Scale-8 (MMAR-8) and the missing/shortened dialysis sessions in the following six months. Of 208 patients approached, 202 (97.1%) agreed to participate. One hundred twenty-three patients (60.9%) were males and mean age was 52.8 ± 14.8 years-old. The median time on hemodialysis was 36 months (IQR, 12, 84). 82 (40.6%) patients obtained a MMAS-8 score <6 and were considered as having 'poor adherence'. Overall, the mean score of medication adherence was low (5.7 ± 2.1). About adherence to hemodialysis sessions, patients missed a total of 234 (1.6%) hemodialysis sessions. Forty-eight patients (23.7%) missed an average of at least three sessions in six months. Regarding adherence to medication, there was no association in the uni- or multivariate analysis between religiosity dimensions and MMAS-8 score. After adjustment, resilience was positively associated with MMAS-8 score (standardized β coefficient .239, p = .016). Organized and intrinsic religiosity were associated with adherence to dialysis sessions (standardized β coefficient .258, p = .004 and .231, p = .026, respectively). Interestingly, opposite to medication adherence, more resilient patients were associated with less adherence to hemodialysis sessions (standardized β coefficient -.296, p = .001). Religiosity was associated with dialysis adherence but not with medication adherence. Resilience was associated with higher medication adherence but lower adherence to dialysis sessions.

Background/aims: Glomerulopathy patients are prone to developing transitory reduced glomerular filtration rate (GFR), which can be difficult to differentiate from irreversible chronic kidney disease (CKD). Renal ultrasound can be useful, but differently from renal length, quantitative renal echogenicity has not been formerly evaluated regarding its capacity to identify irreversible advanced CKD., Methods: A prospective study was performed, where quantitative renal echogenicity was performed during renal biopsy in patients with suspected glomerular disease (n=197). Quantitative echogenicity was measured as the inverse of the ratio between the mean pixel densities of the renal cortex and adjacent liver using ScionImage software. Patients were followed during a six-months period to ascertain irreversible advanced CKD. Quantitative renal echogenicity and histopathology parameters discriminatory capacity were compared regarding their capacity to detect advanced and irreversible CKD - estimated GFR less than 30mL/min/1.73m2 confirmed after a six-month follow-up., Results: At renal biopsy, the mean eGFR was 53.9±33.6 mL/min/1.73m2 and 63 (32.0%) patients had an eGFR less than 30 mL/min/1.73m2. Mean kidney/liver echogenicity ratio was 1.06±0.19 and it was inversely correlated with eGFR at follow-up (r=-0.684, p<0.001). Multivariate analysis was performed to create a histopathology index that correctly identifies irreversible advanced CKD. Renal echogenicity discriminatory capacity to identify irreversible advanced CKD was 0.793 (0.719 -0.867), similar to the histopathology index. Elevated renal echogenicity with best discriminatory capacity was a kidney/liver ratio greater than 1.15. This cutoff had a predictive positive value of 92% in patients with eGFR less than 30mL/min/1.73m2., Conclusion: Quantitative renal echogenicity can be a useful tool in patients with glomerular disease and normal kidney size (>8cm) to identify those patients with irreversible advanced CKD., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background: Ischemia/reperfusion (I/R) in kidney is commonly related to acute kidney injury (AKI), essentially through oxidative stress. (-)-α-Bisabolol is a sesquiterpene isolated from the essential oil of a variety of plants, including chamomile, which has important antioxidant activity., Study Design: This study intends to evaluate the nephroprotective activity of (-)-α-bisabolol (Bis) in both in vivo and in vitro models of kidney I/R., Methods: Male Wistar rats were submitted to right nephrectomy, followed by ischemia by clamping of the renal artery in the left kidney for 60min. and 48h of reperfusion. The animals were treated orally with Bis (100mg/kg) or vehicle for 24h after reperfusion, and placed in metabolic cages, to evaluate water consumption, diuresis, urinary osmolality, classic biochemical markers and urinary KIM-1 (kidney injury molecule-1). Additionally, the left kidney was collected for histological evaluation and determination of glutathione (GSH) and Thiobarbituric Acid Reactive Substances (TBARS) levels. Tubular epithelial cells LLC-MK2 were used to assess Bis effect on in vitro I/R, by MTT assay. It was performed the cellular respiration tests by flow cytometry: evaluation of the production of cytoplasmic reactive oxygen species by DCFH-DA assay and mitochondrial transmembrane potential analysis with the dye rhodamine 123., Results: I/R caused alterations in diuresis, water intake, urinary osmolality, plasmatic creatinine, urea and uric acid, creatinine clearance, proteinuria and microalbuminuria. Treatment with Bis ameliorated all of these parameters. Also, KIM-1 level enhanced by I/R was also diminished in groups treated with Bis. The histological examination showed that Bis attenuated the morphological changes caused by I/R, markedly vascular congestion and intratubular deposits of proteinaceous material. Additionally, Bis was able to reduce the changes observed in TBARS and GSH levels in kidney tissue. In in vitro assay, Bis was capable to partially protect the cell lineage against cell damage induced by I/R., Conclusion: (-)-α-Bisabolol has a nephroprotective effect in kidney I/R, with antioxidant effect. Moreover, this result seems to be associated to a direct protective effect on tubular epithelia., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objectives: To assess the impact of the percentage of fluid infused as Lactated Ringer (%LR) during the first 2 days of ICU admission in hospital mortality and occurrence of acute kidney injury., Design: Retrospective cohort., Setting: Analysis of a large public database (Multiparameter Intelligent Monitoring in Intensive Care-II)., Patients: Adult patients with at least 2 days of ICU stay, admission creatinine lower than 5 mg/dL, and that received at least 500 mL of fluid in the first 48 hours., Interventions: None., Measurement and Main Results: 10,249 patients were included in mortality analysis and 8,085 were included in the acute kidney injury analysis. For acute kidney injury analysis, we excluded patients achieving acute kidney injury criteria in the first 2 days of ICU stay. Acute kidney injury was defined as stage 2/3 Kidney Disease: Improving Global Outcomes creatinine criteria and was assessed from days 3-7. The effects of %LR in both outcomes were assessed through logistic regression controlling for confounders. Principal component analysis was applied to assess the effect of volume of each fluid type on mortality. Higher %LR was associated with lower mortality and less acute kidney injury. %LR effect increased with total volume of fluid infused. For patients in the fourth quartile of fluid volume (> 7 L), the odds ratio for mortality for %LR equal to 75% versus %LR equal to 25% was 0.50 (95% CI, 0.32-0.79; p < 0.001). Principal component analysis suggested that volume of Lactated Ringer and 0.9% saline infused had opposite effects in outcome, favoring Lactated Ringer., Conclusions: Higher %LR was associated with reduced hospital mortality and with less acute kidney injury from days 3-7 after ICU admission. The association between %LR and mortality was influenced by the total volume of fluids infused.

Purpose of Review: To describe recent advances in the understanding of the role of fluid composition in renal outcomes in critically ill patients., Recent Findings: The debate on fluid composition is now focused in a pragmatic discussion on fluid electrolyte composition. The resurgence of this debate was propelled by several observational studies that suggested that balanced (i.e., low chloride) solutions were associated with less acute kidney injury in critically ill patients. Nevertheless, a cluster randomized trial failed to show any benefit of balanced solutions. This trial, however, may have failed to detect an effect because of low global illness severity and little fluid infused. If balanced solutions are to be associated with less acute kidney injury, it will probably be in high risk, aggressively resuscitated patients. Additionally, the causal loop involving unbalanced solution infusion, induction of hyperchloremia and acute kidney injury is yet to be closed. Other factors, such as buffer type, speed of infusion and temperature, among others, may also be important., Summary: Recent evidence suggests that crystalloid fluid composition matters and can influence renal outcomes in critically ill patients. Further studies should assess the impact and cost-efficiency of balanced solutions in the context of high-risk scenarios.

Objective: Acute kidney injury is a common occurrence after pediatric cardiac surgery and is associated with adverse patient outcomes. Syndecan-1 is a biomarker of endothelial glycocalyx damage, and its early increment after surgery can be associated with acute kidney injury., Methods: We performed a prospective cohort study with 289 patients aged less than 18 years who underwent cardiac surgery at 1 reference institution. Postoperative plasma syndecan-1 was collected within the first 2 hours after cardiac surgery. Severe acute kidney injury, defined according to Kidney Disease: Improving Global Outcomes stage 2 or 3, doubling of serum creatinine from the preoperative value, or need for dialysis during hospitalization, was the main outcome. Analyses were adjusted for clinical variables and "renal angina index" components (early decrease in estimated creatinine clearance from baseline and increase in percent of intensive care unit fluid overload on the first postoperative day)., Results: Plasma syndecan-1 levels measured early in the postoperative period were independently associated with severe acute kidney injury. The accuracy of postoperative syndecan-1 for the diagnosis of severe acute kidney injury was moderate (area under the curve receiver operating characteristic, 0.77; 95% confidence interval, 0.68-0.85). The addition of syndecan-1 improved the discrimination capacity of a clinical model from 0.80 to 0.86 (P = .004) and improved risk prediction, as measured by net reclassification improvement and integrated discrimination improvement. Postoperative sundecan-1 levels also were independently associated with longer length of intensive care unit and hospital stay., Conclusions: Postoperative plasma syndecan-1 is associated with subsequent severe acute kidney injury and poor outcomes among children undergoing cardiac surgery. It may be useful to identify patients who are at increased risk for acute kidney injury after cardiac surgery., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Aims: Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury., Main Methods: Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9)., Key Findings: Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury., Significance: Acute ischemic kidney injury is exacerbated by acidic conditions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objectives: Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is limited to patients undergoing cardiac surgery. There are no data about its association with oliguria and AKI in critically ill patients., Design, Setting, Participants, & Measurements: We obtained data from the Multiparameter Intelligent Monitoring in Intensive Care II database (2001-2008). Patient selection criteria included adult patients in their first intensive care unit (ICU) admission, need for mechanical ventilation, and treatment with propofol or midazolam. Propensity score analysis (1:1) was used and renal-related outcomes (AKI, oliguria, cumulative fluid balance, and need for RRT) were evaluated during the first 7 days of ICU stay., Results: There were 1396 propofol/midazolam-matched patients. AKI in the first 7-day ICU time period was statistically lower in propofol-treated patients compared with midazolam-treated patients (55.0% versus 67.3%, P<0.001). Propofol was associated with lower AKI incidence using both urine output (45.0% versus 55.7%, P<0.001) and serum creatinine criteria (28.8% versus 37.2%, P=0.001). Patients receiving propofol had oliguria (<400 ml/d) less frequently (12.4% versus 19.6%, P=0.001) and had diuretics prescribed less often (8.5% versus 14.3%, P=0.001). In addition, during the first 7 days of ICU stay, patients receiving propofol less frequently achieved cumulative fluid balance >5% of body weight (50.1% versus 58.3%, P=0.01). The need for RRT in the first 7 days of ICU stay was also less frequent in propofol-treated patients (3.4% versus 5.9%, P=0.03). ICU mortality was lower in propofol-treated patients (14.6% versus 29.7%, P<0.001)., Conclusions: In this large, propensity-matched ICU population, patients treated with propofol had a lower risk of AKI, fluid-related complications, and need for RRT., (Copyright © 2015 by the American Society of Nephrology.)

Introduction: Acute kidney injury (AKI) remains a great problem in clinical practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological process. Propolis is a natural polyphenol-rich resinous substance collected by honeybees from a variety of plant sources that has anti-inflammatory and anti-oxidative properties. Red propolis (RP) protection in renal I/R injury was investigated., Methods: Male Wistar rats underwent unilateral nephrectomy and contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At 48 h after reperfusion, renal function was assessed and kidneys were removed for analysis., Results: I/R increased plasma levels of creatinine and reduced creatinine clearance (CrCl), and RP provided protection against this renal injury. Red propolis significantly improves oxidative stress parameters when compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in I/R rats compared with the IR-RP rats. RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and increased heme-oxygenase expression in renal tissue., Conclusion: Red propolis protects kidney against acute ischemic renal failure and this protection is associated with reduced oxidative stress and eNOS and heme-oxygenase up regulation., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: Glomerulopathy is a group of diseases that affect mainly young adults. Endothelial dysfunction, atherosclerosis, and increased cardiac mortality can complicate the evolution of such patients. However, there is no study evaluating endothelial glycocalyx in this pathology., Methods: This cross-sectional study included 49 patients with untreated primary nephrotic syndrome that were otherwise healthy. In addition to routine laboratory measurements, syndecan-1, intercellular adhesion molecule-1 (ICAM-1), and e-selectin were measured. Moreover, flow-mediated dilation (FMD) was used as the main endothelial function surrogate., Results: Of the 49 patients with nephrotic syndrome, 25 (51.0%) were females. The mean age of patients was 39.0±12.1y. FMD was reduced in nephrotic patients in comparison with controls (3.7±1.7 vs. 6.6±1.1%, p<0.001). Nephrotic patients had higher levels of ICAM-1 (616.6±219.7 vs. 356.9±102.0ng/ml, p<0.001) and syndecan-1 (180.3±64.1 vs. 28.2±9.8ng/ml, p<0.001). No significant difference was observed regarding e-selectin (129.9±54.2 vs. 120.2±61.5ng/ml, p=0.489). After adjusting for age and glomerular filtration rate, syndecan-1 was significantly associated with 24-h urinary protein excretion, LDL-cholesterol, HDL-cholesterol, and triglycerides. While age, LDL-cholesterol, and 24-h urinary protein excretion were associated with FMD in the multivariate analysis, when syndecan-1, ICAM-1, and e-selectin were added to the model, only syndecan-1 was independently associated with FMD., Conclusions: We demonstrated that syndecan-1, a marker of endothelial glycocalyx damage, is increased in patients with nephrotic syndrome and near-normal renal function. Moreover, we determined its association with nephrotic syndrome features and suggest it can have a role in the endothelial dysfunction of these patients., (Copyright © 2015. Published by Elsevier B.V.)

Objective: To investigate the associations between the 2 main components of metabolic acidosis (unmeasured anions [UA] and hyperchloremia) with serum albumin and intact parathormone (iPTH) in patients with advanced chronic kidney disease., Design and Methods: Cross-sectional study with advanced chronic kidney disease patients (estimated glomerular filtration rate <30 mL/minute/1.73 m(2)) not receiving phosphate binders, alkali therapy, or vitamin D analogs. Arterial blood sample was collected for biochemical and blood gas analysis. UA and strong ion difference (SID) were calculated according to quantitative acid-base analysis. Reduced SID was used as a measure of hyperchloremia., Main Outcome Measures: Serum albumin and parathormone (iPTH)., Results: A total of 383 patients were included with a mean age of 64.7 ± 16.3 year and a mean estimated glomerular filtration rate of 19.9 ± 12.1 mL/minute/1.73 m(2). Among patients with metabolic acidosis, 45.7% had metabolic acidosis exclusively because of UA and 53.7% had a hyperchloremic component (either mixed metabolic acidosis or pure hyperchloremic metabolic acidosis). Considering the main acid-base status determinants, only UA had a significant correlation with serum albumin (r = -0.278, P < .001). There was no correlation between serum albumin and SID (r = 0.083, P = .156). This is in opposition to serum iPTH, where there was no correlation with UA (r = 0.082, P = .114), but an inverse correlation between iPTH and SID was observed (r = -0.228, P < .001). Multiple linear regressions with all acid-base determinants confirmed these findings., Conclusions: Our data brings further knowledge on the associations between metabolic acidosis with bone disorders and nutritional status, suggesting that the two main metabolic acidosis components (UA and hyperchloremia) have different effects on serum parathormone and serum albumin., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P < 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P < 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage., (© The American Society of Tropical Medicine and Hygiene.)