Avaliação comparativa da mecânica ventilatória de pacientes com lesão renal aguda submetidos a hemodiálise diária ou a diálise peritoneal contínua

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação do gasto energético de repouso em pacientes com sepse associada ou não à lesão renal aguda

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Avaliação do efeito do pré e pós-condicionamento em modelo de isquemia renal transitória: estudo comparativo experimental em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ventilator-induced lung injury and acute respiratory distress syndrome: a basic science review

Acute respiratory distress syndrome is the most severe manifestation of acute lung injury and it is associated with high mortality rate. Despite better understanding of ARDS pathophysiology, its mechanism is still unclear. Mechanical ventilation is the main ARDS supportive treatment. However, mechanical ventilation is a non-physiologic process and complications are associated with its application. Mechanical ventilation may induce lung injury, referred to as ventilator-induced lung injury. Frequently, VILI is related to macroscopic injuries associated with alveolar rupture. The present article is a review of the literature on ventilator-induced lung injury in acute respiratory distress syndrome. Animal and human studies were reviewed. We mainly selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications.

Effect of felodipine on myocardial and renal injury induced by aldosterone-high salt hypertension in uninephrectomized rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Formyl-peptide receptor is not involved in the protection afforded by annexin 1 in murine acute myocardial infarct

Recent interest in the annexin 1 field has come from the notion that specific G-protein-coupled receptors, members of the formyl-peptide receptor (FPR) family, appear to mediate the anti-inflammatory actions of this endogenous mediator. Administration of the annexin 1 N-terminal derived peptide Ac2-26 to mice after 25 min ischemia significantly attenuated the extent of acute myocardial injury as assessed 60 min postreperfusion. Evident at the dose of 1 mg/kg (similar to9 nmol per animal), peptide Ac2-26 cardioprotection was intact in FPR null mice. Similarly, peptide Ac2-26 inhibition of specific markers of heart injury (specifically myeloperoxidase activity, CXC chemokine KC contents, and endogenous annexin 1 protein expression) was virtually identical in heart samples collected from wild-type and FPR null mice. Mouse myocardium expressed the mRNA for FPR and the structurally related lipoxin A(4) receptor, termed ALX; thus, comparable equimolar doses of two ALX agonists (W peptide and a stable lipoxin A4 analog) exerted cardioprotection in wild-type and FPR null mice to an equal extent. Curiously, marked (>95%) blood neutropenia produced by an anti-mouse neutrophil serum did not modify the extent of acute heart injury, whereas it prevented the protection afforded by peptide Ac2-26. Thus, this study sheds light on the receptor mechanism(s) mediating annexin 1-induced cardioprotection and shows a pivotal role for ALX and circulating neutrophil, whereas it excludes any functional involvement of mouse FPR. These mechanistic data can help in developing novel therapeutics for acute cardioprotection.

Immunohistochemical characterisation of probable intravascular haematopoiesis in the vasa rectae of the renal medulla in acute tubular necrosis

Immunohistochemistry was applied to identify the nature of the nucleated cells that accumulate in the vasa rectae of the corticomedullary junction in acute tubular necrosis. In all 6 cases studied, there were intravascular cells that reacted with monoclonal antibodies to erythroblast, macrophages, myeloid cells, T and B lymphocytes and rare megakaryocytes. The findings are consistent with the occurrence of intravascular haematopoiesis in the renal medulia in acute tubular necrosis.

Acute renal failure in renal allograft recipients and patients with native kidneys

In order to evaluate the role of underlying disease in the high mortality observed in acute renal failure (ARF) and risk factors related to the development of oliguric ARF in renal allograft recipients, two groups were selected: 34 patients with native kidneys, aged 16 and 57 years, and presenting ischemic ARF caused by cardiovascular collapse, with no signs of infection at the time of diagnosis; and 34 renal allograft recipients who developed ARF immediately after transplantation, without rejection. ARF was defined either as 30% increase of basal plasmatic creatinine in patients with native kidneys or non-normalization of plasmatic creatinine at day 5 after transplantation in renal allograft recipients; oliguria as diuresis ≤ 400 mL/24 h. There were no differences in age, male frequency, oliguria presence and duration, need for dialysis, and infection episodes for renal allograft recipients and patients with native kidneys. The development of sepsis (3% and 41%) and death rate (3% and 44%) were higher in patients with native kidneys (p < 0.01). The renal allograft recipients with both oliguric (n = 18) and nonoliguric (n = 16) ARF were evaluated and no difference was observed in the recipient's age, donor's age, cold ischemia time, time elapsed until plasmatic creatinine normalization, donor's plasmatic creatinine or urea, and mean arterial pressure. No differences were observed between the groups regarding frequency of infection episodes during ARF and frequency of death. In conclusion, renal allograft recipients presented a lower death rate and were less susceptible to sepsis. Cold ischemia time, age, and hemodynamic characteristics of the donor did not affect the development of oliguria.

Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Bothrops leucurus venom induces nephrotoxicity in the isolated perfused kidney and cultured renal tubular epithelia

Bites from snake (Bothrops genus) cause local tissue damage and systemic complications, which include alterations such as hemostatic system and acute renal failure (ARF). Recent studies suggest that ARF pathogenesis in snakebite envenomation is multifactorial and involves hemodynamic disturbances, immunologic reactions and direct nephrotoxicity. The aim of the work was to investigate the effects of the Bothrops leucurus venom (BlV) in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin-Darby Canine kidney). BlV (10 μg/mL) reduced the perfusion pressure at 90 and 120 min. The renal vascular resistance (RVR) decreased at 120 min of perfusion. The effect on urinary flow (UF) and glomerular filtration rate (GFR) started 30 min after BlV infusion, was transient and returned to normal at 120 min of perfusion. It was also observed a decrease on percentual tubular transport of sodium (%TNa+) at 120 min and of chloride (%TCl-) at 60 and 90 min. The treatment with BlV caused decrease in cell viability to the lowest concentration tested with an IC50 of 1.25 μg/mL. Flow cytometry with annexin V and propidium iodide showed that cell death occurred predominantly by necrosis. However, a cell death process may involve apoptosis in lower concentrations. BlV treatment (1.25 μg/mL) led to significant depolarization of the mitochondrial membrane potential and, indeed, we found an increase in the expression of cell death genes in the lower concentrations tested. The venom also evoked an increase in the cytosolic Ca2+ in a concentration dependent manner, indicating that Ca2+ may participate in the venom of B. leucurus effect. The characterization of the effects in the isolated kidney and renal tubular cells gives strong evidences that the acute renal failure induced by this venom is a result of the direct nephrotoxicity which may involve the cell death mechanism. © 2012.

Treatment of adriamycin-induced nephropathy with erythropoietin and G-CSF

Background: Granulocyte colony-stimulating factor (G-CSF) and Erythropoietin (EPO) are known to stimulate the growth and differentiation of progenitor cells to prevent acute renal injury. This study aimed to assess the use of growth factors to mobilize stem cell in a mouse model of adriamycin-induced chronic kidney disease. Methods: All animals were injected with adriamycin for kidney injury and allocated into three treatment groups (G-CSF, EPO and G-CSF + EPO), and a control group (adriamycin alone). Results: Number of atrophic sites, glomerulosclerosis rate and interstitial fibrosis severity score were assessed in all groups. In all treatment groups, histologic parameters did not significantly differ, but were lower than in the control group (P<.001). Scal and CD34 expressions among treatment groups showed no statistically significant difference, but were higher than in the control group (P<.0001). CD105 expression was higher in EPO and G+EPO as compared to G-CSF and the control group (P<.0001), with no statistically significant difference between the latter two groups (P = NS). Conclusion: G-CSF and EPO had a histologic protective effect, while treatment with EPO + G-CSF had no additive effects in a model of adriamycin-induced chronic kidney disease. © 2013 Societá Italiana di Nefrologia.

Proteção renal com eritropoetina em modelo de isquemia renal no rato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

NGAL como marcador precoce de lesão renal em ratos submetidos à isquemia renal sob anestesia geral balanceada

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Interferência do parecoxibe sobre a função renal e lesão de rins submetidos ao estresse isquêmico: trabalho experimental em ratos com uso de NGAL como marcador da função renal

Pós-graduação em Anestesiologia - FMB