LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais

URI Permanente desta comunidade

https://observatorio.fm.usp.br/handle/OPI/3642
O Laboratório de Pesquisa Básica em Doenças Renais é ligado ao Departamento de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo (FMUSP).

Linhas de pesquisa: estresse oxidativo; função tubular e sua implicação hidroeletrolítica; insuficiência renal aguda; nefrotoxicidade por drogas; rim e doenças infecciosas; heterogeneidade das arteríolas glomerulares e sua implicação na reatividade vascular e efeitos da hipercolesterolemia na função hepática.

Site oficial: http://limhc.fm.usp.br/portal/lim12-laboratorio-de-pesquisa-basica-em-doencas-renais/

Índice h

Scopus: 44
Exibir mais

Navegar

Coleções desta Comunidade

Agora exibindo 1 - 3 de 3

Submissões Recentes

conferenceObject
Uric Acid Oxidation Products Correlate with Sepsis and Promote Modification on Serum Albumin in Intensive Care Unit Patients
(2023) SILVA, Railmara; ALVES, Priscilla D. M.; BRANDAO, Luciana S.; VILEIGAS, Danielle; SOUZA JUNIOR, Douglas Ricardo de; RONSEIN, Graziella Eliza; ANDRADE, Lucia; MEOTTI, Flavia
article 6 Citação(ões) na Scopus
Single High-dose of Liposomal Amphotericin B in Human Immunodeficiency Virus (HIV)/AIDS-related Disseminated Histoplasmosis: A Randomized Trial
(2023) PASQUALOTTO, Alessandro C.; LANA, Daiane Dalla; GODOY, Cassia S. M.; LEITAO, Terezinha do Menino Jesus Silva; BAY, Monica B.; DAMASCENO, Lisandra Serra; SOARES, Renata B. A.; KIST, Roger; SILVA, Larissa R.; WILTGEN, Denusa; MELO, Marineide; GUIMARAES, Taiguara F.; GUIMARAES, Marilia R.; VECHI, Hareton T.; MESQUITA, Jaco R. L. de; MONTEIRO, Gloria Regina de G.; ADENIS, Antoine; BAHR, Nathan C.; SPEC, Andrej; BOULWARE, David R.; ISRAELSKI, Dennis; CHILLER, Tom; FALCI, Diego R.
This is the first trial to demonstrate that AIDS patients with disseminated histoplasmosis can be safely and effectively treated with a single high dose of liposomal amphotericin B (10 mg/kg). Background Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. Methods Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. Results A total of 118 subjects were randomized, and median CD4(+) counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). Conclusions One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.
article 0 Citação(ões) na Scopus
The impact of obesity in hospitalized patients with COVID-19: a retrospective cohort study
(2024) CARRA, Fabio Alfano; MELO, Maria Edna de; STUMPF, Matheo A. M.; CERCATO, Cintia; FERNANDES, Ariana E.; MANCINI, Marcio C.; HIROTA, Adriana; KANASIRO, Alberto Kendy; CRESCENZI, Alessandra; FERNANDES, Amanda Coelho; MIETHKE-MORAIS, Anna; BELLINTANI, Arthur Petrillo; CANASIRO, Artur Ribeiro; CARNEIRO, Barbara Vieira; ZANBON, Beatriz Keiko; PINHEIRO, Bernardo; BATISTA, Senna Nogueira; NICOLAO, Bianca Ruiz; BESEN, Bruno Adler Maccagnan Pinheiro; BISELLI, Bruno; MACEDO, Bruno Rocha De; TOLEDO, Caio Machado Gomes De; CARVALHO, Carlos Roberto Ribeiro De; MOL, Caroline Gomes; STIPANICH, Cassio; BUENO, Caue Gasparotto; GARZILLO, Cibele; TANAKA, Clarice; FORTE, Daniel Neves; JOELSONS, Daniel; ROBIRA, Daniele; COSTA, Eduardo Leite Vieira; SILVA JUNIOR, Elson Mendes Da; REGALIO, Fabiane Aliotti; SEGURA, Gabriela Cardoso; LOURO, Giulia Sefrin; MARCELINO, Gustavo Brasil; HO, Yeh-Li; FERREIRA, Isabela Argollo; GOIS, Jeison Oliveira; SILVA-JR, Joao Manoel Da; JUNIOR, Jose Otto Reusing; RIBEIRO, Julia Fray; FERREIRA, Juliana Carvalho; GALLETI, Karine Vusberg; SILVA, Katia Regina; ISENSEE, Larissa Padrao; OLIVEIRA, Larissa Santos; TANIGUCHI, Leandro Utino; LETAIF, Leila Suemi; LIMA, Ligia Trombetta; PARK, Lucas Yongsoo; NETTO, Lucas Chaves; NOBREGA, Luciana Cassimiro; HADDAD, Luciana Bertocco Paiva; HAJJAR, Ludhmila Abrahao; MALBOUISSON, Luiz Marcelo Sa; PANDOLFI, Manuela Cristina Adsuara; PARK, Marcelo; CARMONA, Maria Jose Carvalho; ANDRADE, Maria Castilho Prandini H.; SANTOS, Mariana Moreira; BATELOCHE, Matheus Pereira; SUIAMA, Mayra Akimi; OLIVEIRA, Mayron Faria de; SOUSA, Mayson Laercio; GARCIA, Michelle Louvaes; HUEMER, Natassja; MENDES, Pedro Vitale; LINS, Paulo Ricardo Gessolo; SANTOS, Pedro Gaspar Dos; MOREIRA, Pedro Ferreira Paiva; GUAZZELLI, Renata Mello; REIS, Renato Batista Dos; DALTRO-OLIVEIRA, Renato; ROEPKE, Roberta Muriel Longo; PEDRO, Rodolpho Augusto Moura; KONDO, Rodrigo; RACHED, Samia Zahi; FONSECA, Sergio Roberto Silveira Da; BORGES, Thais Sousa; FERREIRA, Thalissa; JUNIOR, Vilson Cobello; SALES, Vivian Vieira Tenorio; FERREIRA, Willaby Serafim Cassa
Background Obesity is believed to be a risk factor for COVID-19 and unfavorable outcomes, although data on this remains to be better elucidated.Objective To evaluate the impact of obesity on the endpoints of patients hospitalized due to SARS-CoV-2.Methods This retrospective cohort study evaluated patients hospitalized at a tertiary hospital (Hospital das Cl & iacute;nicas da Faculdade de Medicina da USP) from March to December 2020. Only patients positive for COVID-19 (real-time PCR or serology) were included. Data were collected from medical records and included clinical and demographic information, weight and height, SAPS-3 score, comorbidities, and patient-centered outcomes (mortality, and need for mechanical ventilation, renal replacement therapy, or vasoactive drugs). Patients were divided into categories according to their BMI (underweight, eutrophic, overweight and obesity) for comparison porpoise.Results A total of 2547 patients were included. The mean age was 60.3 years, 56.2% were men, 65.2% were white and the mean BMI was 28.1 kg/m(2). SAPS-3 score was a risk factor for all patient-centered outcomes (HR 1.032 for mortality, OR 1.03 for dialysis, OR 1.07 for vasoactive drug use, and OR 1.08 for intubation, p < 0.05). Male sex increased the risk of death (HR 1.175, p = 0.027) and dialysis (OR 1.64, p < 0.001), and underweight was protective for vasoactive drug use (OR 0.45, p = 0.027) and intubation (OR 0.31, p < 0.003).Conclusion Obesity itself was not an independent factor for worse patient-centered outcomes. Critical clinical state (indirectly evaluated by SAPS-3) appears to be the most important variable related to hard outcomes in patients infected with COVID-19.
article 0 Citação(ões) na Scopus
article 0 Citação(ões) na Scopus
Critically ill patients with COVID-19-associated acute kidney injury treated with kidney replacement therapy: Comparison between the first and second pandemic waves in São Paulo, Brazil
(2023) SAMAAN, Farid; FREITAS, Rafaela Andrade Penalva; VIANA, Renata; GAMBARO, Livia; CUNHA, Karlla; VIEIRA, Tales Dantas; FEITOSA, Valkercyo; CORREA, Eric Aragao; MACIEL, Alexandre Toledo; ARANHA, Sylvia; OSAWA, Eduardo Atsushi; PILLAR, Roberta; FLATO, Elias Marcos da Silva; SILVA, Renata Cristina da; CARNEIRO, Elisa; SOUZA, Fabrizzio Batista Guimaraes de Lima; ROSSI, Paula Regina Gan; ABUD, Munira Bittencourt; KONIGSFELD, Henrique Pinheiro; SILVA, Riberto Garcia da; SOUZA, Ricardo Barbosa Cintra de; COUTINHO, Saurus Mayer; GOES, Miguel angelo; SILVA, Barbara Antunes Bruno da; ZANETTA, Dirce Maria Trevisan; BURDMANN, Emmanuel Almeida
IntroductionThis study aimed to compare the characteristics and outcomes of critically ill patients with COVID-19-associated acute kidney injury (AKI) who were treated with kidney replacement therapy (KRT) in the first and second waves of the pandemic in the megalopolis of Sao Paulo, Brazil.MethodsA multicenter retrospective study was conducted in 10 intensive care units (ICUs). Patients aged >= 18 years, and treated with KRT due to COVID-19-associated AKI were included. We compared demographic, laboratory and clinical data, KRT parameters and patient outcomes in the first and second COVID-19 waves.ResultsWe assessed 656 patients (327 in the first wave and 329 in the second one). Second-wave patients were admitted later (7.1 +/- 5.0 vs. 5.6 +/- 3.9 days after the onset of symptoms, p<0.001), were younger (61.4 +/- 13.7 vs. 63.8 +/- 13.6 years, p = 0.023), had a lower frequency of diabetes (37.1% vs. 47.1%, p = 0.009) and obesity (29.5% vs. 40.0%, p = 0.007), had a greater need for vasopressors (93.3% vs. 84.6%, p<0.001) and mechanical ventilation (95.7% vs. 87.8%, p<0.001), and had higher lethality (84.8% vs. 72.7%, p<0.001) than first-wave patients. KRT quality markers were independently associated with a reduction in the OR for death in both pandemic waves.ConclusionsIn the Sao Paulo megalopolis, the lethality of critically ill patients with COVID-19-associated AKI treated with KRT was higher in the second wave of the pandemic, despite these patients being younger and having fewer comorbidities. Potential factors related to this poor outcome were difficulties in health care access, lack of intra-hospital resources, delay vaccination and virus variants.
article 0 Citação(ões) na Scopus
A clinical model to predict successful renal replacement therapy (RRT) discontinuation in patients with Acute Kidney Injury (AKI)
(2023) VALLE, Eduardo de Oliveira; SMOLENTZOV, Igor; GORZONI, Joao Lucas Martins; SALGADO, Isabela Cavalcante; MAINARDES, Lorena Catelan; GOMES, Vanessa Oliveira; MELO JUNIOR, Charles Hamilton; RODRIGUES, Camila Eleuterio; VIEIRA JUNIOR, Jose Mauro Vieira
Introduction: Ideal timing of Renal Replacement Therapy (RRT) discontinuation in Acute Kidney Injury (AKI) is still unknown. We aimed to study the role of creatinine-related variables in predicting RRT successful discontinuation and to propose a clinical predictive score.Methods: In this single-centre retrospective study, we evaluated all AKI patients in whom RRT was interrupted for at least 48 hours. Patients who were still RRT-independent 7 days after initial RRT cessation were included in the ""Success"" group and opposed to the ""Failure"" group. We evaluated baseline characteristics and variables collected at the time of RRT interruption, as well as the Kinetic estimated Glomerular Filtration Rate (KeGFR), the simple variation in serum Creatinine (Delta sCr), and the incremental creatinine ratio on the first three days after RRT interruption. Multivariable analysis was performed to evaluate prediction of success. Internal validation using a simple binomial generalized regression model with Lasso estimation and 5-fold cross validation method was performed. Results: We included 124 patients, 49 in the ""Failure"" group and 75 in the ""Success"" group. All creatinine-related variables predicted success in simple and multiple logistic regression models. The best model generated a clinical score based on the odds ratio obtained for each variable and included urine output, non-renal SOFA score, fluid balance, serum urea, serum potassium, blood pH, and the variation in sCr values after RRT discontinuation. The score presented an area under the ROC of 0.86 (95% CI 0.76-1.00). Conclusion: Creatinine variation between the first 2 consecutive days after RRT discontinuation might predict success in RRT discontinuation. The developed clinical score based on these variables might be a useful clinical decision tool to guide hemodialysis catheter safe removal.
article 2 Citação(ões) na Scopus
TREATMENT WITH HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN A PIG MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY: EFFECTS ON MICROVASCULAR ENDOTHELIAL CELLS AND TUBULAR CELLS IN THE KIDNEY
(2023) MAIA, Debora Rothstein Ramos; OTSUKI, Denise Aya; RODRIGUES, Camila Eleuterio; ZBORIL, Sabrina; SANCHES, Talita Rojas; NETO, Amaro Nunes Duarte; ANDRADE, Lucia; AULER, Jose Otavio Costa
Background: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 x 106 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappa B) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-kappa B signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.
article 2 Citação(ões) na Scopus
Can a Therapeutic Strategy for Hypotension Improve Cerebral Perfusion and Oxygenation in an Experimental Model of Hemorrhagic Shock and Severe Traumatic Brain Injury?
(2023) BALZI, Ana Paula de Carvalho Canela; OTSUKI, Denise Aya; ANDRADE, Lucia; PAIVA, Wellingson; SOUZA, Felipe Lima; AURELIANO, Luiz Guilherme Cernaglia; MALBOUISSON, Luiz Marcelo Sa
BackgroundRestoration of brain tissue perfusion is a determining factor in the neurological evolution of patients with traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of HS without neurological damage, it was observed that the use of fluids or vasoactive drugs was effective in restoring brain perfusion; however, only terlipressin promoted restoration of cerebral oxygenation and lower expression of edema and apoptosis markers. It is unclear whether the use of vasopressor drugs is effective and beneficial during situations of TBI. The objective of this study is to compare the effects of resuscitation with saline solution and terlipressin on cerebral perfusion and oxygenation in a model of TBI and HS.MethodsThirty-two pigs weighing 20-30 kg were randomly allocated into four groups: control (no treatment), saline (60 ml/kg of 0.9% NaCl), terlipressin (2 mg of terlipressin), and saline plus terlipressin (20 ml/kg of 0.9% NaCl + 2 mg of terlipressin). Brain injury was induced by lateral fluid percussion, and HS was induced through pressure-controlled bleeding, aiming at a mean arterial pressure (MAP) of 40 mmHg. After 30 min of circulatory shock, resuscitation strategies were initiated according to the group. The systemic and cerebral hemodynamic and oxygenation parameters, lactate levels, and hemoglobin levels were evaluated. The data were subjected to analysis of variance for repeated measures. The significance level established for statistical analysis was p < 0.05.ResultsThe terlipressin and saline plus terlipressin groups showed an increase in MAP that lasted until the end of the experiment (p < 0.05). There was a notable increase in intracranial pressure in all groups after starting treatment for shock. Cerebral perfusion pressure and cerebral oximetry showed no improvement after hemodynamic recovery in any group. The groups that received saline at resuscitation had the lowest hemoglobin concentrations after treatment.ConclusionsThe treatment of hypotension in HS with saline and/or terlipressin cannot restore cerebral perfusion or oxygenation in experimental models of HS and severe TBI. Elevated MAP raises intracranial pressure owing to brain autoregulation dysfunction caused by TBI.
article 1 Citação(ões) na Scopus
Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats
(2023) SHIMIZU, Maria Heloisa Massola; VOLPINI, Rildo Aparecido; BRAGANCA, Ana Carolina de; NASCIMENTO, Mariana Moura; BERNARDO, Desiree Rita Denelle; SEGURO, Antonio Carlos; CANALE, Daniele
Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3 beta (GSK3 beta) inhibition protects against AKI basically through its critical role in tubular epithelial cell apoptosis, inflammation and fibrosis. Treatment with a single dose of lithium, an inhibitor of GSK3 beta, accelerated recovery of renal function in cisplatin and ischemic/reperfusion-induced AKI models. We aimed to evaluate the efficacy of a single dose of lithium in the treatment of rhabdomyolysis-induced AKI. Male Wistar rats were allocated to four groups: Sham, received saline 0.9% intraperitoneally (IP); lithium (Li), received a single IP injection of lithium chloride (LiCl) 80 mg/kg body weight (BW); glycerol (Gly), received a single dose of glycerol 50% 5 mL/kg BW intramuscular (IM); glycerol plus lithium (Gly+Li), received a single dose of glycerol 50% IM plus LiCl IP injected 2 hours after glycerol administration. After 24 hours, we performed inulin clearance experiments and collected blood / kidney / muscle samples. Gly rats exhibited renal function impairment accompanied by kidney injury, inflammation and alterations in signaling pathways for apoptosis and redox state balance. Gly+Li rats showed a remarkable improvement in renal function as well as kidney injury score, diminished CPK levels and an overstated decrease of renal and muscle GSK3 beta protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NF kappa B and caspase renal protein expression and increased the antioxidant component MnSOD. Lithium treatment attenuated renal dysfunction in rhabdomyolysis-associated AKI by improving inulin clearance and reducing CPK levels, inflammation, apoptosis and oxidative stress. These therapeutic effects were due to the inhibition of GSK3 beta and possibly associated with a decrease in muscle injury.
article 0 Citação(ões) na Scopus
International Perspectives on GFR Estimation and Race-Based Adjustments
(2023) EL-KHOURY, Joe M.; KARGER, Amy B.; CAVALIER, Etienne; KALYESUBULA, Robert; TEO, Boon Wee; SILVA, Veronica T. Costa e; INKER, Lesley A.