Comorbidities, acute kidney injury and long-term mortality in elderly patients hospitalized because of hip fracture: a moderation analysis.

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.

Endothelial biomarkers as predictors for haemodialysis need in severe leptospirosis patients (Weil's disease).

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.

Biomarkers of acute kidney injury in pediatric cardiac surgery.

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.

Attributable nephrotoxicity of vancomycin in critically ill patients: a marginal structural model study.

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 ß-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.

Cognitive impairment, endothelial biomarkers and mortality in maintenance haemodialysis patients: a prospective cohort study.

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.

Fibroblast growth factor 23, endothelium biomarkers and acute kidney injury in critically-ill patients.

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.

Angiopoietin-2 as a predictor of acute kidney injury in critically ill patients and association with ARDS.

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.

Kinetic estimated glomerular filtration rate in critically ill patients: beyond the acute kidney injury severity classification system.

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 m2) to 27.8% (KeGFR < 30 ml/min/1.73 m2). 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 m2 but no AKI; otherwise, mortality increased to 40% when both AKI stage 3 and KeGFR < 30 ml/min/1.73 m2 were present. In relation to another outcome-renal replacement therapy (RRT)-patients with the worst achieved KeGFR < 30 ml/min/1.73 m2 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 m2 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.

Resilience, religiosity and treatment adherence in hemodialysis patients: a prospective study.

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 ß coefficient .239, p = .016). Organized and intrinsic religiosity were associated with adherence to dialysis sessions (standardized ß 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 ß 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.

Syndecan-1 in Acute Decompensated Heart Failure--Association With Renal Function and Mortality.

BACKGROUND: Heart failure (HF) is a leading cause of hospitalization throughout the world, and the mortality rate remains elevated. HF is frequently complicated by acute kidney injury (AKI), worsening the patient's prognosis. There have been no studies evaluating the role that endothelial glycocalyx damage plays in HF patients and its association with AKI and mortality. METHODS AND RESULTS: We measured several endothelial biomarkers in 201 consecutive patients with acute decompensated HF (ADHF) during emergency department (ED) admission. In-hospital mortality, AKI development and 6-month mortality rates were assessed. ADHF patients with worsening renal function had higher levels of syndecan-1 but not those patients with stable chronic kidney disease. Syndecan-1 levels during ED admission were predictive for AKI during the hospital stay (AUC 0.741, P<0.001) and had an even better discriminatory capacity in more severe AKI (AUC 0.812, P<0.001). Additionally, after adjusting for several confounding factors, including biomarkers of endothelial function and endothelial cell activation, syndecan-1 remained associated with in-hospital mortality rates. On a Cox multivariate analysis regression, syndecan-1 was associated with 6-month mortality rates. CONCLUSIONS: The concentration of syndecan-1, a marker of glycocalyx damage measured during ED admission, is valuable in assessing the risk of developing AKI and in-hospital mortality. Its association with mortality is strong after 6-month follow-up.

Hemodialysis-specific factors associated with salivary flow rates.

The saliva is important to maintain the integrity of tissues and teeth, besides having microbial activity. Hemodialysis (HD) patients usually have reduced salivary flow rate (SFR) and are exposed to all its associated complications. The aim of the present study was to identify HD-related factors associated with reduced SFR. A cross-sectional study was performed with maintenance HD patients. Stimulated whole saliva was collected before and after HD. Xerostomia was assessed through the validated xerostomia inventory and thirst through the dialysis thirst inventory. Parameters of dental health status were obtained by the decayed, missed, and filled teeth index and community periodontal index. One hundred twenty-eight patients (66 males) participated in this study. Stimulated SFR before HD was 0.38 ± 0.28 mL/min. In univariate analysis and after adjusting for several factors, serum urea before HD session, serum intact parathormone (iPTH), calcium-phosphorus product (Ca×Pi), serum ferritin, and number of medications were negatively correlated with SFR in univariate analysis. Moreover, patients taking sevelamer had reduced SFR in comparison with those not receiving it (SFR 0.32 ± 0.19 vs. 0.44 ± 0.23 mL/min, P = 0.003). At multivariate analysis, including dialysis and nondialysis-related factors, age, elevated pre-HD serum urea, higher Ca×Pi product, higher iPTH, and sevelamer use remained as factors that were independently associated with a reduced SFR. After dialysis, there was a significant increment in SFR (0.39 ± 0.28 vs. 0.60 ± 0.34 mL/min, P < 0.001). Several HD-related features were associated with reduced SFR, including serum urea, sevelamer use, and bone and mineral disorders markers.

Metabolic acidosis components in advanced chronic kidney disease: association with serum albumin and parathyroid hormone.

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.

Urinary monocyte chemotactic protein-1 (MCP-1) in leprosy patients: increased risk for kidney damage.

BACKGROUND: We aimed to evaluate urinary MCP-1 and oxidative stress through urinary malondialdehyde (MDA) in leprosy and correlate them with traditional, but less sensitive markers of renal disease. METHODS: This is a cross-sectional study of 44 patients with diagnosis of leprosy and no previous treatment. Skin smear was assessed through a bacteriological index - from 0 to 6+. Glomerular filtration rate (GFR), protein excretion rate, microalbuminuria, urinary oxidative stress, malondialdehyde (MDA) and urinary MCP-1 were measured. Also, high- sensitivity C-reactive protein (hs-CRP) was measured in the blood. Fifteen healthy subjects composed a control group. RESULTS: Age and gender were similar between leprosy patients and control groups. No patient had a GFR < 60 mL/min/1.73 m2 or albumin excretion rate greater than 30 mg/g-Cr. Leprosy patients had higher urinary protein excretion (97.6 ± 69.2 vs. 6.5 ± 4.3 mg/g-Cr, p < 0.001), urinary MCP-1 (101.0 ± 79.8 vs. 34.5 ± 14.9 mg/g-Cr, p = 0.006) and urinary MDA levels (1.77 ± 1.31 vs. 1.27 ± 0.66 mmol/g-Cr, p = 0.0372) than healthy controls. There was a positive correlation between urinary MCP-1 and bacteriological index in skin smears (r = 0.322, p = 0.035), urinary protein excretion (r = 0.547, p < 0.001), albumin excretion rate (r = 0.414, p = 0.006) and urinary MDA (r = 0.453, p = 0.002). After adjusting for hs-CRP, urinary MCP-1 remained correlated with albumin excretion rate (rpartial = 0.483, p = 0.007) and MDA levels (rpartial = 0.555, p = 0.001). CONCLUSION: Leprosy patients with no clinical kidney disease have increased urinary MCP-1 mainly in lepromatous polar form. Inflammatory (MCP-1) and oxidative stress markers suggest leprosy patients are at high risk of developing kidney disease.

Endothelium-related biomarkers enhanced prediction of kidney support therapy in critically ill patients with non-oliguric acute kidney injury.

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.

Defining reduced urine output in neonatal ICU: importance for mortality and acute kidney injury classification.

BACKGROUND: Acute kidney injury (AKI) is an independent risk factor for mortality in adults and children. Generally, urine output (UO) < 1 mL/kg/h is accepted as oliguria in neonates, although it has not been systematically studied. pRIFLE criteria suggest UO cut-offs similar to those of the adult population (0.3 and 0.5 mL/kg/h). The aim of the present study was to investigate UO in correlation with mortality in critically ill neonates and suggest changes in the pRIFLE definition of reduced diuresis. METHODS: A retrospective cohort study was performed in an eight-bed neonatal intensive care unit (NICU). UO was systematically measured by diaper weight each 3 h. Discriminatory capacity to predict mortality of UO was measured and patients were divided according to UO ranges: G1 > 1.5 mL/kg/h; G2 1.0-1.5 mL/kg/h; G3 0.7-1.0 mL/kg/h and G4 < 0.7 mL/kg/h. These ranges were incorporated to pRIFLEGFR criteria and its performance was evaluated. RESULTS: Of 384 patients admitted at the NICU during the study period, 72 were excluded and overall mortality was 12.8%. UO showed good performance for mortality prediction (area under the curve 0.789, P < 0.001). There was a stepwise increase in hospital mortality according to UO groups after controlling for SNAPPE-II and diuretic use. Using these UO ranges with pRIFLE improves its discriminatory capacity (area under the receiver operating characteristic curve 0.882 versus 0.693, P < 0.05). CONCLUSIONS: UO is a predictor of mortality in NICU. An association between a UO threshold < 1.5 mL/kg/h and mortality was observed, which is higher than the previously published pRIFLE thresholds. Adopting higher values of UO in pRIFLE criteria can improve its capacity to detect AKI severity in neonates.

Kidney Disease Improving Global Outcomes or creatinine kinetics criteria in acute kidney injury: a proof of concept study.

BACKGROUND: It has been recently mathematically demonstrated that the percentage increase in serum creatinine (SCr) can delay acute kidney injury (AKI) diagnosis in patients with previous chronic kidney disease (CKD). Based on creatinine (Cr) kinetics, it was suggested a new AKI classification using absolute increase in SCr elevation over specified time periods. However, this classification has not been evaluated in clinical studies. METHODS: A prospective cohort study evaluated myocardial infarction patients during the first 7 days of hospital stay with daily SCr measurements. They were classified using Kidney Disease Improving Global Outcomes (KDIGO) and Cr kinetics systems. Both classifications were compared by net reclassification improvement (NRI) and area under the receiver operator characteristic (AuROC) curve regarding hospital mortality. RESULTS: A total of 584 patients were included, of which 34.1% had previous CKD. Patients had more AKI by KDIGO than by Cr kinetics criteria (25.7 versus 18.0%, P < 0.001) and 81 patients (13.9%) had different AKI severity classification. Patients with AKI by KDIGO criteria and non-AKI by Cr kinetics had higher hospital mortality rates than patients with non-AKI using both classifications [adjusted mortality odds ratios (ORs): 4.753; 95% confidence interval (CI): 1.119-9.023, P = 0.014]. In patients with previous CKD, NRI analysis was 6.2% favoring Cr kinetics criteria. However, there was no difference using the AuROC curve analysis. In patients with no previous CKD, NRI analysis was 33.0%, favoring KDIGO, and this was in accordance with a better AuROC curve (0.828 versus 0.664, P < 0.05). CONCLUSIONS: AKI classification proposed by a Cr kinetics model can be superior when diagnosing patients with previous CKD. However, KDIGO had a better performance in patients with no previous CKD.

Restless legs syndrome and quality of sleep in patients with glomerulopathy.

BACKGROUND: Despite a confirmed association between restless legs syndrome (RLS) and end-stage renal disease (ESRD), there is no study on patients presenting with nephrotic syndrome (NS). To investigate the frequency of RLS and poor quality sleep in NS-patients secondary to primary glomerulopathy with nearly normal glomerular filtration rate (GFR) and its associated factors. METHODS: Patients with NS, defined as 24 h-urine protein greater than 3.5 g/1.73 m2 and hypoalbuminemia, (n = 99, 53 women) and a mean age of 36±11 years were studied. Age and sex-matched controls were used to compare RLS and poor sleep quality prevalence. Standardized RLS questionnaire formulated by the International Restless Legs Syndrome and Pittsburgh Sleep Quality Index (PSQI) were used. RESULTS: RLS was more frequent in NS-patients than in controls (22.8 vs. 4.0%, p = 0.01). Mean time since diagnosis (52.2±34.1 vs. 28.6±22.5 months, p < 0.01) and 24 h-proteinuria (3.7±1.3 vs. 2.6±0.6 g/1.73 m2, p = 0.001) were greater in NS-patients with RLS those not presenting RLS. Association between RLS with 24 h-proteinuria [OR = 2.31; p = 0.007; 95% CI 1.87-2.89] and time since diagnosis [OR = 1.10; p = 0.003; CI = 1.02-1.39] were identified even after controlling for age, GFR and diabetes. Sleep quality was poor in NS-patients than in controls (mean PSQI score 7.35±3.7 vs. 5.2±3.0, p = 0.003). In NS-patients, only RLS was associated with poor sleep quality (OR = 1.20; p = 0.004). CONCLUSION: Poor quality sleep and RLS are frequent in NS-patients without ESRD. Pathophysiology of this association must be further investigated.

Syndecan-1 predicts hemodynamic instability in critically ill patients under intermittent hemodialysis.

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.

Importance of anemia in the chronic Cardiorenal syndrome: effects on renal function after heart transplantation.

BACKGROUND: Cardiorenal syndrome has been recently divided into 5 categories, according to acute or chronic evolution and primary organ dysfunction. Anemia can also accompany this disorder, leading to a more complex situation. This study aims to analyze the renal outcomes of patients, specifically patients with chronic Cardiorenal syndrome, with or without anemia, long-term after heart transplantation. MATERIAL/METHODS: This was a retrospective cohort study on chronic Cardiorenal syndrome patients submitted to heart transplantation. Patients were divided according to presence of anemia and renal dysfunction before heart transplantation. RESULTS: A total of 108 patients (92 males) with the mean age of 45±12 years were included. The etiologies of the heart failure were hypertensive dilated myocardiopathy (66%), ischemic (14%) and Chagasic (12%). Before the heart transplantation, 51 patients had an eGFR less than 60 mL/min. From these, 24 had concomitant anemia. One year after the transplantation, patients with previous isolated renal dysfunction ameliorates eGFR (45±11 vs. 65±26 mL/min, p<0.001), while those patients with previous renal dysfunction and anemia presented no improvement (eGFR 44±14 vs. 47±13 mL/min, p=0.619) 1 year after heart transplantation. Moreover, higher hemoglobin was an independent predictor of eGFR improvement after heart transplantation when associated with previous renal dysfunction (OR 1.8; CI 1.2-3.6, p<0.01 for each hemoglobin increment of 1 g/dL). CONCLUSIONS: Patients with isolated Cardiorenal syndrome presented partial renal function recovery after heart transplantation, while the presence of cardiorenal anemia was a marker of renal function non-recovery 1 year after heart transplantation.