Alexandre Braga Libório - Profile on Academia.edu (original) (raw)

Papers by Alexandre Braga Libório

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

Nephrology Dialysis Transplantation, 2013

Background. Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin rece... more Background. Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to 'functional' postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for 'structural' AKI, measured with new urinary biomarkers, is unknown. Methods. The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals

Research paper thumbnail of Biomarkers of acute kidney injury in pediatric cardiac surgery

Biomarkers of acute kidney injury in pediatric cardiac surgery

Pediatric Nephrology

Research paper thumbnail of Intraoperative systemic biomarkers predict post-liver transplantation acute kidney injury

Intraoperative systemic biomarkers predict post-liver transplantation acute kidney injury

European Journal of Gastroenterology & Hepatology

Research paper thumbnail of Early renal replacement therapy in acute kidney injury: a piece in the puzzle

Annals of Translational Medicine

Research paper thumbnail of Oral Health conditions in hemodialysis Patients

International Journal of Advanced Engineering Research and Science

Objectives: This study aimed to assess oral health status and self-perceived oral health in hemod... more Objectives: This study aimed to assess oral health status and self-perceived oral health in hemodialysis (HD) patients. Materials and Methods: Thedecayed, missing and filled teeth (DMFT) index and the community periodontal (CPI) index were used to assess oral health status and self-perceived oral health in 128 HD patients.Salivary flow (SF) and pH were also measured. Results: Mean age was 56.2±17.1 years and mean DMFT was 23±9.14. There were 41 (32%) edentulous participants and 81 (94.3%) non-edentulous participants presented periodontal alterations. SF was normal (≥1.0ml/min) in five (3.9%) participants before HD and in 17 (13.3%) participants after HD. SF was very low (≤ 0.3ml/min) in 60 (46.9%) participants before HD and in 26 (20.3%) participants after HD. The difference in SF before (0.39±0.28ml/min) and after (0.60±0.34ml/min) HD was significant (p<0.001). There was a negative correlation between salivary flow and age before (r=-0.188, p=0.033) and after (r=-0.261, p=0.003) HD. Conclusions: Despite the increase in salivary flow after HD sessions, the rates were still below the normal levels, thus indicating the need for special care. Clinical Relevance: Our findings show that the oral health care professional should provide preventive and restorative treatment to HD patients and should be included in themultiprofessionalhealth team managing the care of HD patients.

Research paper thumbnail of Respiratory parameters and acute kidney injury in acute respiratory distress syndrome: a causal inference study

Annals of Translational Medicine

Background: Assess the respiratory-related parameters associated with subsequent severe acute kid... more 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.

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

Respirology

Background and objective: Angiopoietin-2 (AGPT2) has been proposed as a key mediator of organ dys... more 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.

Research paper thumbnail of Prediction of 60-Day Case Fatality in Critically Ill Patients Receiving Renal Replacement Therapy

Prediction of 60-Day Case Fatality in Critically Ill Patients Receiving Renal Replacement Therapy

SHOCK

Research paper thumbnail of Visceral leishmaniasis-associated nephropathy in hospitalized Brazilian patients: new insights based on kidney injury biomarkers

Tropical medicine & international health : TM & IH, Jan 10, 2018

To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management o... more To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis. Prospective study with 50 hospitalized VL patients. AKI biomarkers, i.e., 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. VL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia, hematologic and hepatic disorders. AKI was found in 46%, and 1 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...

Research paper thumbnail of Effects of respiratory muscle training on endothelium and oxidative stress biomarkers in hemodialysis patients: A randomized clinical trial

Respiratory medicine, 2018

Hemodialysis (HD) patients have altered pulmonary function and this is associated with impaired e... more 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. 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), For...

Research paper thumbnail of Kinetic estimated glomerular filtration rate in critically ill patients: beyond the acute kidney injury severity classification system

Critical care (London, England), Jan 18, 2017

Although significant advances have been achieved in acute kidney injury (AKI) research following ... more 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. 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. 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...

Research paper thumbnail of Endothelial glycocalyx damage and renal dysfunction in HIV patients receiving combined antiretroviral therapy

Endothelial glycocalyx damage and renal dysfunction in HIV patients receiving combined antiretroviral therapy

AIDS research and human retroviruses, Jul 6, 2017

Widespread use of combined antiretroviral therapy (cART) increase HIV patients' life expectan... more Widespread use of combined antiretroviral therapy (cART) increase HIV patients' life expectancy, however favored the development of kidney and cardiovascular diseases. The aim of this study was to investigate endothelial glycocalyx 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 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 <60mL/min. All HIV patients had higher systemic syndecan-1 compared with healthy controls (71.8±25....

Research paper thumbnail of SP205ENDOTHELIAL Glycocalyx Damage and Renal Dysfunction in Hiv Patients Receiving Combined Antiretroviral Therapy

Nephrology Dialysis Transplantation, 2016

Research paper thumbnail of SP211HYPONATREMIA and Mortality in Patients with Visceral Leishmaniasis and Acute Kidney Injury

SP211HYPONATREMIA and Mortality in Patients with Visceral Leishmaniasis and Acute Kidney Injury

Nephrology Dialysis Transplantation, 2016

Research paper thumbnail of Resilience, religiosity and treatment adherence in hemodialysis patients: a prospective study

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

Psychology, health & medicine, Jun 1, 2016

Resilience and religiosity have received attention as an important process in the experience and ... more 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 (I...

Research paper thumbnail of Syndecan-1 improves severe acute kidney injury prediction after pediatric cardiac surgery

The Journal of thoracic and cardiovascular surgery, 2016

Acute kidney injury is a common occurrence after pediatric cardiac surgery and is associated with... more 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. 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). Plasma syndecan-...

Research paper thumbnail of Metabolic acidosis aggravates experimental acute kidney injury

Life sciences, Jan 7, 2016

Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that ma... more 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. Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45min, followed by 48h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28M NH4Cl solution plus I/R, n=9). Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, ...

Research paper thumbnail of Rosiglitazona, agonista do PPAR-y "Peroxisome Proliferator-Activated Receptor-y" reverte a nefrotoxicidade induzida pelo tenofovir-DF

To characterize the mechanisms of tenofovir disoproxil fumarate (TDF)induced nephrotoxicity and t... more To characterize the mechanisms of tenofovir disoproxil fumarate (TDF)induced nephrotoxicity and the protective effects of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-γ agonist. Methods: Rats were treated for 30 days with one of two TDF doses (50 or 300 mg/kg of food), to which RSG (92 mg/kg of food) was added for the last 15 days. Biochemical parameters were measured, and renal tissue was extracted for immunoblotting. Results: Mean daily ingestion was comparable among all the treated groups. Highdose TDF induced severe renal failure accompanied by reduced expression of endothelial nitric-oxide synthase and intense renal vasoconstriction. All of these features were ameliorated by RSG administration. Low-dose TDF did not alter the glomerular filtration rate but induced significant phosphaturia, proximal tubular acidosis and polyuria, as well as reducing urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. No Fanconi's syndrome was identified (proteinuria was normal and there was no glycosuria). Treatment with RSG reversed TDF-induced tubular nephrotoxicity, normalizing urinary biochemical parameters and membrane transporter protein expression. 14 Conclusion: These findings have potential clinical applications in patients presenting with TFV-induced nephrotoxicity, especially in those presenting with hypophosphatemia or a reduction in glomerular filtration rate.

Research paper thumbnail of Renal Outcomes in Critically Ill Patients Receiving Propofol or Midazolam

Clinical Journal of the American Society of Nephrology, 2015

Background and objectives Propofol has been shown to provide protection against renal ischemia/re... more 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.

Research paper thumbnail of Urinary KIM-1 in children undergoing nephrotoxic antineoplastic treatment: a prospective cohort study

Urinary KIM-1 in children undergoing nephrotoxic antineoplastic treatment: a prospective cohort study

Pediatric Nephrology, 2015

Acute kidney injury (AKI) is a significant complication in patients with cancer, and nephrotoxic ... more Acute kidney injury (AKI) is a significant complication in patients with cancer, and nephrotoxic drugs are among the most common causes of AKI. To date, there is no study evaluating the potential role of renal biomarkers in children receiving nephrotoxic chemotherapy. A prospective study was conducted in children receiving methotrexate (MTX) or platinum-based treatment. Urinary kidney injury molecule-1 (KIM-1) was measured 24 h after the initiation of the chemotherapy infusion, and serum creatinine (sCr) was measured prior to drug infusion and at 24, 48, 72, and 96 h, 1 and 2 weeks, and 3 months post-initiation of treatment. A total of 64 children were evaluated, of whom 21 (32.8 %) developed AKI. The majority had AKI stage 1 (n = 12, 57.1 %) and only one developed AKI stage 3. Median values of urinary KIM-1 were higher in patients with AKI than in those without AKI [10.7, interquartile range (IQR) 1.6-17.9 vs. 4.3 (IQR 1.3-6.1) ng/mg creatinine; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01]. Urinary KIM-1 showed good discrimination for AKI in patients receiving nephrotoxic chemotherapy, with an area under the receiver operator characteristic curve for AKI up to 1 week later of 0.82 (95% confidence interval 0.66-0.95). Even when measured only 24 h after drug infusion, urinary KIM-1 still showed good discrimination to predict persistent renal impairment three months later. Urinary KIM-1 measured 24 h after the start of drug infusion has the potential to detect early AKI in pediatric patients treated with MTX or platinum-class drugs.

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

Nephrology Dialysis Transplantation, 2013

Background. Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin rece... more Background. Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to 'functional' postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for 'structural' AKI, measured with new urinary biomarkers, is unknown. Methods. The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals

Research paper thumbnail of Biomarkers of acute kidney injury in pediatric cardiac surgery

Biomarkers of acute kidney injury in pediatric cardiac surgery

Pediatric Nephrology

Research paper thumbnail of Intraoperative systemic biomarkers predict post-liver transplantation acute kidney injury

Intraoperative systemic biomarkers predict post-liver transplantation acute kidney injury

European Journal of Gastroenterology & Hepatology

Research paper thumbnail of Early renal replacement therapy in acute kidney injury: a piece in the puzzle

Annals of Translational Medicine

Research paper thumbnail of Oral Health conditions in hemodialysis Patients

International Journal of Advanced Engineering Research and Science

Objectives: This study aimed to assess oral health status and self-perceived oral health in hemod... more Objectives: This study aimed to assess oral health status and self-perceived oral health in hemodialysis (HD) patients. Materials and Methods: Thedecayed, missing and filled teeth (DMFT) index and the community periodontal (CPI) index were used to assess oral health status and self-perceived oral health in 128 HD patients.Salivary flow (SF) and pH were also measured. Results: Mean age was 56.2±17.1 years and mean DMFT was 23±9.14. There were 41 (32%) edentulous participants and 81 (94.3%) non-edentulous participants presented periodontal alterations. SF was normal (≥1.0ml/min) in five (3.9%) participants before HD and in 17 (13.3%) participants after HD. SF was very low (≤ 0.3ml/min) in 60 (46.9%) participants before HD and in 26 (20.3%) participants after HD. The difference in SF before (0.39±0.28ml/min) and after (0.60±0.34ml/min) HD was significant (p<0.001). There was a negative correlation between salivary flow and age before (r=-0.188, p=0.033) and after (r=-0.261, p=0.003) HD. Conclusions: Despite the increase in salivary flow after HD sessions, the rates were still below the normal levels, thus indicating the need for special care. Clinical Relevance: Our findings show that the oral health care professional should provide preventive and restorative treatment to HD patients and should be included in themultiprofessionalhealth team managing the care of HD patients.

Research paper thumbnail of Respiratory parameters and acute kidney injury in acute respiratory distress syndrome: a causal inference study

Annals of Translational Medicine

Background: Assess the respiratory-related parameters associated with subsequent severe acute kid... more 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.

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

Respirology

Background and objective: Angiopoietin-2 (AGPT2) has been proposed as a key mediator of organ dys... more 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.

Research paper thumbnail of Prediction of 60-Day Case Fatality in Critically Ill Patients Receiving Renal Replacement Therapy

Prediction of 60-Day Case Fatality in Critically Ill Patients Receiving Renal Replacement Therapy

SHOCK

Research paper thumbnail of Visceral leishmaniasis-associated nephropathy in hospitalized Brazilian patients: new insights based on kidney injury biomarkers

Tropical medicine & international health : TM & IH, Jan 10, 2018

To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management o... more To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis. Prospective study with 50 hospitalized VL patients. AKI biomarkers, i.e., 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. VL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia, hematologic and hepatic disorders. AKI was found in 46%, and 1 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...

Research paper thumbnail of Effects of respiratory muscle training on endothelium and oxidative stress biomarkers in hemodialysis patients: A randomized clinical trial

Respiratory medicine, 2018

Hemodialysis (HD) patients have altered pulmonary function and this is associated with impaired e... more 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. 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), For...

Research paper thumbnail of Kinetic estimated glomerular filtration rate in critically ill patients: beyond the acute kidney injury severity classification system

Critical care (London, England), Jan 18, 2017

Although significant advances have been achieved in acute kidney injury (AKI) research following ... more 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. 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. 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...

Research paper thumbnail of Endothelial glycocalyx damage and renal dysfunction in HIV patients receiving combined antiretroviral therapy

Endothelial glycocalyx damage and renal dysfunction in HIV patients receiving combined antiretroviral therapy

AIDS research and human retroviruses, Jul 6, 2017

Widespread use of combined antiretroviral therapy (cART) increase HIV patients' life expectan... more Widespread use of combined antiretroviral therapy (cART) increase HIV patients' life expectancy, however favored the development of kidney and cardiovascular diseases. The aim of this study was to investigate endothelial glycocalyx 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 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 <60mL/min. All HIV patients had higher systemic syndecan-1 compared with healthy controls (71.8±25....

Research paper thumbnail of SP205ENDOTHELIAL Glycocalyx Damage and Renal Dysfunction in Hiv Patients Receiving Combined Antiretroviral Therapy

Nephrology Dialysis Transplantation, 2016

Research paper thumbnail of SP211HYPONATREMIA and Mortality in Patients with Visceral Leishmaniasis and Acute Kidney Injury

SP211HYPONATREMIA and Mortality in Patients with Visceral Leishmaniasis and Acute Kidney Injury

Nephrology Dialysis Transplantation, 2016

Research paper thumbnail of Resilience, religiosity and treatment adherence in hemodialysis patients: a prospective study

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

Psychology, health & medicine, Jun 1, 2016

Resilience and religiosity have received attention as an important process in the experience and ... more 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 (I...

Research paper thumbnail of Syndecan-1 improves severe acute kidney injury prediction after pediatric cardiac surgery

The Journal of thoracic and cardiovascular surgery, 2016

Acute kidney injury is a common occurrence after pediatric cardiac surgery and is associated with... more 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. 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). Plasma syndecan-...

Research paper thumbnail of Metabolic acidosis aggravates experimental acute kidney injury

Life sciences, Jan 7, 2016

Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that ma... more 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. Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45min, followed by 48h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28M NH4Cl solution plus I/R, n=9). Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, ...

Research paper thumbnail of Rosiglitazona, agonista do PPAR-y "Peroxisome Proliferator-Activated Receptor-y" reverte a nefrotoxicidade induzida pelo tenofovir-DF

To characterize the mechanisms of tenofovir disoproxil fumarate (TDF)induced nephrotoxicity and t... more To characterize the mechanisms of tenofovir disoproxil fumarate (TDF)induced nephrotoxicity and the protective effects of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-γ agonist. Methods: Rats were treated for 30 days with one of two TDF doses (50 or 300 mg/kg of food), to which RSG (92 mg/kg of food) was added for the last 15 days. Biochemical parameters were measured, and renal tissue was extracted for immunoblotting. Results: Mean daily ingestion was comparable among all the treated groups. Highdose TDF induced severe renal failure accompanied by reduced expression of endothelial nitric-oxide synthase and intense renal vasoconstriction. All of these features were ameliorated by RSG administration. Low-dose TDF did not alter the glomerular filtration rate but induced significant phosphaturia, proximal tubular acidosis and polyuria, as well as reducing urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. No Fanconi's syndrome was identified (proteinuria was normal and there was no glycosuria). Treatment with RSG reversed TDF-induced tubular nephrotoxicity, normalizing urinary biochemical parameters and membrane transporter protein expression. 14 Conclusion: These findings have potential clinical applications in patients presenting with TFV-induced nephrotoxicity, especially in those presenting with hypophosphatemia or a reduction in glomerular filtration rate.

Research paper thumbnail of Renal Outcomes in Critically Ill Patients Receiving Propofol or Midazolam

Clinical Journal of the American Society of Nephrology, 2015

Background and objectives Propofol has been shown to provide protection against renal ischemia/re... more 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.

Research paper thumbnail of Urinary KIM-1 in children undergoing nephrotoxic antineoplastic treatment: a prospective cohort study

Urinary KIM-1 in children undergoing nephrotoxic antineoplastic treatment: a prospective cohort study

Pediatric Nephrology, 2015

Acute kidney injury (AKI) is a significant complication in patients with cancer, and nephrotoxic ... more Acute kidney injury (AKI) is a significant complication in patients with cancer, and nephrotoxic drugs are among the most common causes of AKI. To date, there is no study evaluating the potential role of renal biomarkers in children receiving nephrotoxic chemotherapy. A prospective study was conducted in children receiving methotrexate (MTX) or platinum-based treatment. Urinary kidney injury molecule-1 (KIM-1) was measured 24 h after the initiation of the chemotherapy infusion, and serum creatinine (sCr) was measured prior to drug infusion and at 24, 48, 72, and 96 h, 1 and 2 weeks, and 3 months post-initiation of treatment. A total of 64 children were evaluated, of whom 21 (32.8 %) developed AKI. The majority had AKI stage 1 (n = 12, 57.1 %) and only one developed AKI stage 3. Median values of urinary KIM-1 were higher in patients with AKI than in those without AKI [10.7, interquartile range (IQR) 1.6-17.9 vs. 4.3 (IQR 1.3-6.1) ng/mg creatinine; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01]. Urinary KIM-1 showed good discrimination for AKI in patients receiving nephrotoxic chemotherapy, with an area under the receiver operator characteristic curve for AKI up to 1 week later of 0.82 (95% confidence interval 0.66-0.95). Even when measured only 24 h after drug infusion, urinary KIM-1 still showed good discrimination to predict persistent renal impairment three months later. Urinary KIM-1 measured 24 h after the start of drug infusion has the potential to detect early AKI in pediatric patients treated with MTX or platinum-class drugs.