ORCID Profile
0000-0003-0562-0893
Current Organisations
Universidade de São Paulo
,
University of New South Wales - Randwick Campus
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Publisher: American Physiological Society
Date: 2020
DOI: 10.1152/AJPREGU.00098.2018
Abstract: Sepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by α7-nicotinic acetylcholine receptors (α7nAChRs), which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly ided into four groups: control (sham-operated) cecal ligation and puncture (CLP) alone CLP+WJ-MSCs (1 × 10 6 cells, at 6 h post-CLP) and CLP+methyllycaconitine (MLA)+WJ-MSCs (5 mg/kg body wt, at 5.5 h post-CLP, and 1 × 10 6 cells, at 6 h post-CLP, respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective α7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated α7nAChR expression, as well as reduced the phospho-STAT3-to-total STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.
Publisher: Informa UK Limited
Date: 04-2016
Publisher: Springer Science and Business Media LLC
Date: 08-08-2023
Publisher: Wiley
Date: 25-11-2022
DOI: 10.1111/NEP.14132
Abstract: The current definition of acute kidney injury (AKI) is generic and, based only on markers of function, is unsuitable for guiding in idualized treatment. AKI is a complex syndrome with multiple presentations and causes. Targeted AKI management will only be possible if different phenotypes and subphenotypes of AKI are recognised, based on causation and related pathophysiology. Molecular signatures to identify subphenotypes are being recognised, as specific biomarkers reveal activated pathways. Assessment of in idual clinical risk needs wider dissemination to allow identification of patients at high risk of AKI. New and more timely markers for glomerular filtration rate (GFR) are available. However, AKI diagnosis and classification should not be limited to GFR, but include tubular function and damage. Combining damage and stress biomarkers with functional markers enhances risk prediction, and identifies a population enriched for clinical trials targeting AKI. We review novel developments and aim to encourage implementation of these new techniques into clinical practice as a strategy for in idualizing AKI treatment akin to a precision medicine‐based approach.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/832649
Abstract: Until 15 years ago, vasculogenesis, the formation of new blood vessels from undifferentiated cells, was thought to occur only during embryonic development. The discovery of circulating cells that are able to promote vascular regeneration and repair—the so-called endothelial progenitor cells (EPCs)—changed that, and EPCs have since been studied extensively. It is already known that EPCs include many subtypes of cells that play a variety of roles in promoting vascular growth. Some EPCs are destined to differentiate into endothelial cells, whereas others are capable of promoting and sustaining angiogenesis through paracrine mechanisms. Vasculogenesis and angiogenesis might constitute complementary mechanisms for postnatal neovascularization, and EPCs could be at the core of this process. Although the formation of new blood vessels from preexisting vasculature plays a beneficial role in many physiological processes, such as wound healing, it also contributes to tumor growth and metastasis. However, many aspects of the role played by EPCs in tumor angiogenesis remain unclear. This review aims to address the main aspects of EPCs differentiation and certain characteristics of their main function, especially in tumor angiogenesis, as well as the potential clinical applications.
Publisher: Elsevier BV
Date: 05-2011
Publisher: Cold Spring Harbor Laboratory
Date: 26-10-2021
DOI: 10.1101/2021.10.20.21265300
Abstract: Acute Kidney Injury (AKI) may occur in more than 30% of COVID hospitalized patients, and renal recovery is poorly described. We aimed to evaluate the renal short-term recovery profile of COVID-related AKI (COV+) compared to COVID-unrelated AKI (COV-). case-control retrospective single-center study All patients admitted to the Hospital das Clínicas, University of São Paulo, who recovered AKI from April to June of 2020 (COV+, n=98) and from August to October of 2019 (COV-, n=50) were analyzed. Recovery was defined by spontaneous serum creatinine drop or withdrawal of dialysis. Serum electrolytes were analyzed during the first five days of recovery. Among 333 COV+ patients, 98 recovered from AKI (29.4%), while 50 of 177 COV-patients recovered (28.2%). The COV- group presented higher prevalence of chronic morbidities, while the COV+ group had a worse acute clinical course requiring vasoactive drugs (VAD), mechanical ventilation (MV) and dialysis. COVID-19 diagnosis was associated with need of mecxhanical ventilation, dialysis, presence of fever, and higher use of any diuretic drug during first days of recovery. The presence of fever and mechanical ventilation were the predictors associated with intravascular volume depletion surrogates (daily progressive rising in sodium levels and elevation in serum urea: creatinine ratio). Neither COVID-19 nor diuretics use seem to be independent risk factors for this. Intravascular volume depletion surrogates are more common in short-term AKI-recovery of patients presenting fever and mechanical ventilation, commons features in SARS-CoV2 infection.
Publisher: S. Karger AG
Date: 2018
DOI: 10.1159/000495386
Abstract: b i Background/Aims: /i /b Peritoneal dialysis (PD) has gained interest over the last decade as a viable option for early start dialysis. It is still unknown if shorter break-in periods and less time for proper patient evaluation and training could influence technique survival in comparison to planned-start PD. b i Methods: /i /b A prospective and observational study that compared technique survival in a cohort of patients who started either early or planned PD. Early start PD was defined as break-in period from 3 to 14 days with no previous nephrologist follow-up or patient training. b i Results: /i /b A total of 154 patients were included (40 as early start PD), followed by a median time of 381 days. Comparing early vs. planned-start PD, groups were similar concerning age 56 (40 70) vs. 48 (32 63) years, p=0.071, body mass index (BMI) 23.3 ± 4.2 vs. 23.8 ± 4.0 kg/m sup /sup , p=0.567 and male gender (60 vs. 48%, p=0.201), respectively. Comparing early vs. planned-start groups, there were no differences regarding PD dropout for peritonitis (7.5 vs. 11.4%, p=0.764), catheter dysfunction (12.5 vs. 17.5%, p=0.619) and patient burnout (0 vs. 4.4%, p=0.328), respectively. Less patients in early start group quit PD for peritoneal membrane failure in comparison to planned-start group (2.5 vs. 16.7%, p=0.026). In multivariate cox-regression analysis, the only factors independently associated with technique failure were BMI& #x3e 25 kg/m² (p=0.033) and Diabetes Mellitus (p=0.013), whereas no differences regarding early vs. planned-PD start were observed (p=0.184). b i Conclusion: /i /b Despite the adverse scenario for initiating dialysis, early start PD had similar outcomes in comparison to planned-start PD in long-term follow-up.
Publisher: SAGE Publications
Date: 27-04-2018
Abstract: Acute kidney injury (AKI), characterized by a sharp drop in glomerular filtration, continues to be a significant health burden because it is associated with high initial mortality, morbidity, and substantial health-care costs. There is a strong connection between AKI and mechanisms of senescence activation. After ischemic or nephrotoxic insults, a wide range of pathophysiological events occur. Renal tubular cell injury is characterized by cell membrane damage, cytoskeleton disruption, and DNA degradation, leading to tubular cell death by necrosis and apoptosis. The senescence mechanism involves interstitial fibrosis, tubular atrophy, and capillary rarefaction, all of which impede the morphological and functional recovery of the kidneys, suggesting a strong link between AKI and the progression of chronic kidney disease. During abnormal kidney repair, tubular epithelial cells can assume a senescence-like phenotype. Cellular senescence can occur as a result of cell cycle arrest due to increased expression of cyclin kinase inhibitors (mainly p21), downregulation of Klotho expression, and telomere shortening. In AKI, cellular senescence is aggravated by other factors including oxidative stress and autophagy. Given this scenario, the main question is whether AKI can be repaired and how to avoid the senescence process. Stem cells might constitute a new therapeutic approach. Mesenchymal stem cells (MSCs) can ameliorate kidney injury through angiogenesis, immunomodulation, and fibrosis pathway blockade, as well as through antiapoptotic and promitotic processes. Young umbilical cord–derived MSCs are better at increasing Klotho levels, and thus protecting tissues from senescence, than are adipose-derived MSCs. Umbilical cord–derived MSCs improve glomerular filtration and tubular function to a greater degree than do those obtained from adult tissue. Although senescence-related proteins and microRNA are upregulated in AKI, they can be downregulated by treatment with umbilical cord–derived MSCs. In summary, stem cells derived from young tissues, such as umbilical cord–derived MSCs, could slow the post-AKI senescence process.
Publisher: Bio-Protocol, LLC
Date: 2021
Publisher: Informa UK Limited
Date: 02-2010
DOI: 10.3109/08860220903368567
Abstract: Collapsing glomerulopathy (CG) is a severe form of nephrotic syndrome and has been mostly associated with human immunodeficiency virus (HIV) infection. Treatment response is poor, and the disease frequently leads to end-stage renal disease. More recently, CG has been described in association with other conditions, such as drug exposure and other infections, but renal prognosis remains unfavorable. This paper reports an interesting case of an HIV-negative patient with tuberculosis-related CG who needed dialysis for five months but presented full renal recovery after tuberculosis (TB) treatment and corticotherapy.
Publisher: Wiley
Date: 09-2009
DOI: 10.1111/J.1399-0012.2009.01030.X
Abstract: The delay in the diagnosis of infections can be deleterious in renal transplant recipients. Thus, laboratory tests leading to an earlier diagnosis are very useful for these patients. To assess the behavior of C-reactive protein (CRP) in renal transplant recipients with a diagnosis of cytomegalovirus (CMV) infection, tuberculosis (TB) and bacterial infection (BI). A retrospective analysis of 129 patients admitted at our hospital, from 2006 to 2008 because of CMV, TB or BI, was carried out. Appropriate statistical analysis was done and values were expressed as medians, range. When CRP levels were compared among the groups with CMV disease, TB or BI, the group with CMV disease presented lower levels of CRP (18.4 mg/L, 0.28-44 mg/L) than the TB and BI (p < 0.05) groups. The area under the receiver-operating characteristics curve, distinguishing CMV disease from TB/BI, was 0.96 (p < 0.0001), resulting in 100% sensitivity and 90.63% specificity to detect CMV disease when CRP < 44.5 mg/L. The subgroup analysis of CMV infection showed increasing levels of CRP (0.28, 16 and 29.5 mg/L) in the asymptomatic, symptomatic and invasive disease subgroups, respectively (p < 0.05). The measurement of CRP levels may be a useful tool for differentiating CMV infection from the other types (bacterial or TB) of infection in kidney transplant recipients.
Publisher: Oxford University Press (OUP)
Date: 08-06-2016
Abstract: Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor κB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate.
Publisher: Public Library of Science (PLoS)
Date: 03-08-2016
Publisher: International Scientific Information, Inc.
Date: 12-11-2018
DOI: 10.12659/AJCR.911810
Publisher: Springer Science and Business Media LLC
Date: 25-04-2019
Publisher: Springer Science and Business Media LLC
Date: 12-02-2009
DOI: 10.1038/JHH.2009.3
Publisher: Elsevier BV
Date: 2023
Publisher: American Physiological Society
Date: 15-04-2012
DOI: 10.1152/AJPRENAL.00148.2011
Abstract: The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks, a mechanism to which NF-κB activation is central. Downregulation of endothelial nitric oxide synthase (eNOS) contributes to sepsis-induced endothelial dysfunction. Erythropoietin (EPO) has emerged as a major tissue-protective cytokine in the setting of stress. We investigated the role of EPO in sepsis-related acute kidney injury using a cecal ligation and puncture (CLP) model. Wistar rats were ided into three primary groups: control (sham-operated) CLP and CLP+EPO. EPO (4,000 IU/kg body wt ip) was administered 24 and 1 h before CLP. Another group of rats received N-nitro-l-arginine methyl ester (l-NAME) simultaneously with EPO administration (CLP+EPO+l-NAME). A fifth group (CLP+EPOtreat) received EPO at 1 and 4 h after CLP. At 48 h postprocedure, CLP+EPO rats presented significantly higher inulin clearance than did CLP and CLP+EPO+l-NAME rats hematocrit levels, mean arterial pressure, and metabolic balance remained unchanged in the CLP+EPO rats and inulin clearance was significantly higher in CLP+EPOtreat rats than in CLP rats. At 48 h after CLP, creatinine clearance was significantly higher in the CLP+EPO rats than in the CLP rats. In renal tissue, pre-CLP EPO administration prevented the sepsis-induced increase in macrophage infiltration, as well as preserving eNOS expression, EPO receptor (EpoR) expression, IKK-α activation, NF-κB activation, and inflammatory cytokine levels, thereby increasing survival. We conclude that this protection, which appears to be dependent on EpoR activation and on eNOS expression, is attributable, in part, to inhibition of the inflammatory response via NF-κB downregulation.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2020
DOI: 10.1186/S13063-020-04814-0
Abstract: The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults ( 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. Data Collection: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient’s age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts ( .000 ui/uL) during treatment period. Mild and major bleeding will be defined by hemorrhagic event without clinical impact or hemoglobin (Hb) fall lesser than 1g/dL and hemorrhagic event with clinical impact or Hb fall higher than 1g/dL, respectively. Exclusion criteria: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin) Previous diagnosis of coagulopathy or thrombophilia Contraindication to the use of unfractionated heparin Risk of citrate poisoning - (Lactate 30 mg/dL, international normalized ratio 2.5, Total bilirubin 15 mg/dL) Pregnancy Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. RedCap→ randomization – 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. No blinding – Open label format Total number of patients 90 (45 per group) Trial version 2.0 – ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990 , registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1) In the interest in expediting dissemination of this material, the familiar formatting has been eliminated this Letter serves as a summary of the key elements of the full protocol.
Publisher: Wiley
Date: 06-2017
DOI: 10.14814/PHY2.13262
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.TRANSPROCEED.2015.07.035
Abstract: In the intensive care unit (ICU), mortality is considered higher among renal transplant recipients than among nontransplantation patients. However, data regarding severe complications after kidney transplantation are scarce. In this study, we evaluated all consecutive renal transplant recipients admitted to our ICU between July 2012 and July 2013 (n = 70), comparing their outcomes with those of a control group of nontransplantation patients admitted during the same period (n = 153). Among the transplant recipients, we compared survivors and nonsurvivors to identify predictors of ICU mortality. The mean age of the transplant recipients was 52 ± 13 years. Of the 70 transplant recipients, 18 (25%) required mechanical ventilation, 28 (40%) required inotropic support, and 27 (39%) required hemodialysis, all of which are factors that worsen the prognosis significantly. Twenty-two (31%) of the transplant recipients died in the ICU and 17 (24%) died within 30 days after ICU discharge, rates similar to those observed for the control group. We observed similar mortality between recipient and control groups, albeit the mortality was higher in the clinical group. In the multivariate model, the need for mechanical ventilation and the need for hemodialysis were independently associated with mortality.
Publisher: Public Library of Science (PLoS)
Date: 03-01-2012
Publisher: Springer Science and Business Media LLC
Date: 19-08-2021
DOI: 10.1186/S13054-021-03729-9
Abstract: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV − AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV − AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25–0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV − AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18–0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99–4.68). In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.
No related grants have been discovered for Camila Rodrigues.