Repositório Institucional - Unifesp :: Navegando por Palavras-chave "Nephrotoxicity"

Navegando por Palavras-chave "Nephrotoxicity"

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Acesso aberto (Open Access)
Aspectos moleculares envolvidos na nefrotoxicidade induzida pela cisplatina
(Universidade Federal de São Paulo (UNIFESP), 2017-05-31) Estrela, Gabriel Rufino [UNIFESP]; Araujo, Ronaldo de Carvalho [UNIFESP]; Câmara, Niels Olsen Saraiva [UNIFESP]; Barros, Carlos Castilho de [UNIFESP]; http://lattes.cnpq.br/8098379714093877; http://lattes.cnpq.br/7429609548804288; http://lattes.cnpq.br/8650749833791970; http://lattes.cnpq.br/2039649004832444; Universidade Federal de São Paulo (UNIFESP)
Cisplatin is one of the antitumor agents most commonly used in chemotherapy, but nephrotoxicity is frequent and one of the limitations of its use. There are several mechanisms that contribute to renal dysfunction following exposure to cisplatin: direct tubular toxicity inducing apoptosis, necrosis and inflammation. Kinin B1 receptor is a receptor induced in inflammatory states, it is known that the increase of TNF-α and IL-1β, as well as the activation of NF-κB are able to regulate the expression of this receptor. Recently our group has shown that deletion and blockage of kinin B1 receptor is able to attenuate cisplatin-induced nephrotoxicity. It is known that clearance of cisplatin is primarily dependent on organic transporters, OCT-2 responsible for the transport of cisplatin into the renal epithelial cell and MATE-1, which is responsible for the extrusion of drug in renal cells. Several studies show that both physical exercise and caloric restriction are excellent tools to attenuate the inflammatory response, reducing apoptosis, cytokine expression, production of reactive oxygen species, increase of antioxidants and anti-inflammatory and anti-apoptotic mediators. Because both B1 receptor deletion and antagonism attenuates cisplatin-induced nephrotoxicity, we have examined whether this protection is due to modulation of influx and efflux of cisplatin into the renal cell. In addition, we used physical exercise and caloric restriction against cisplatin-induced nephrotoxicity to see if both tools are able to attenuate renal toxicity. Cisplatin decreases the expression of OCT-2 and MATE-1 in the kidneys, animals knockouts for the B1 receptor are able to preserve the expression of these transporters and present lower concentration of platinum in renal tissue. Moreover, we observed that both physical exercise and caloric restriction are able to attenuate cisplatin-induced nephrotoxicity, decreasing the expression of pro-inflammatory cytokines and apoptosis. Caloric restriction together with physical exercise increases the expression of PPAR-α, but only the restriction increases the expression of PPAR target genes. The combined treatment of caloric restriction with PPAR-α antagonism does not attenuate acute tubular necrosis, shows no decrease in TNF-α expression, and does not demonstrate a decrease in expression in genes related to intrinsic apoptosis. By this we showed that kinin B1 receptor has a role in nephrotoxicity induced by cisplatin and it is by part due to modulation of organic transporters and that some of benefical effects of caloric restriction is mediated by PPAR- α.
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Bothropoides insularis venom cytotoxicity in renal tubular epithelia cells
(Elsevier B.V., 2014-09-15) Mello, Clarissa P.; Morais, Isabel C. O.; Menezes, Ramon R. P. P. B.; Pereira, Gustavo J. S. [UNIFESP]; Torres, Alba F. C.; Lima, Danya B.; Pereira, Ticiana P.; Toyama, Marcos H.; Monteiro, Helena S. A.; Smaili, Soraya Soubhi [UNIFESP]; Martins, Alice M. C.; Univ Fed Ceara; Universidade Federal de São Paulo (UNIFESP); Univ Estadual Paulista
Bothropoides insularis (jararaca-ilhoa) is a native endemic snake limited to the specific region of Queimada Island, on São Paulo coast. Several local and systemic effects have been described due to envenomation caused by it, such as edema, tissue necrosis, hemorrhage and acute renal failure. Our previous studies have shown that Bothropoides insularis venom (BinsV) demonstrated important functional and morphologic alterations in rat isolated kidney, especially decrease in tubular electrolyte transport, osmotic clearance and tubular necrosis. in order to elucidate the direct nephrotoxicity mechanism, the aim of the present study was to investigate BinsV cytotoxicity effect on renal epithelial cells. the treatment with BinsV over MDCK culture decreased cell viability in all concentrations tested with IC50 of 9 mu g/mL. BinsV was able to induce membrane rupture and cell death with phosphatidilserine externalization. Furthermore, BinsV induced ROS overproduction and mitochondrial membrane potential collapse, as well as Bax translocation and caspases 3 and 7 expression. Therefore, these events might be responsible by BinsV-induced cell death caused by mitochondrial dysfunction and ROS overproduction in the direct cytotoxicity process. (C) 2014 Elsevier B.V. All rights reserved.
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Bothrops leucurus venom induces nephrotoxicity in the isolated perfused kidney and cultured renal tubular epithelia
(Elsevier B.V., 2013-01-01) Oliveira de Morais, Isabel Cristina; Costa Torres, Alba Fabiola; Silva Pereira, Gustavo Jose da [UNIFESP]; Pereira, Ticiana Praciano; Pessoa Bezerra de Menezes, Ramon Roseo de Paula; Mello, Clarissa Perdigao; Coelho Jorge, Antonio Rafael; Binda, Alexandre Havt; Toyama, Marcos Hikari; Azul Monteiro, Helena Serra; Smaili, Soraya Soubhi [UNIFESP]; Costa Martins, Alice Maria; Univ Fed Ceara; Universidade Federal de São Paulo (UNIFESP); Paulista State Univ UNESP
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 mu g/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 (CFR) 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 mu g/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 mu g/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. Published by Elsevier B.V.
Acesso aberto (Open Access)
Efeito da lectina de Dioclea violacea na lesão renal aguda induzida pela gentamicina
(Universidade Federal de São Paulo (UNIFESP), 2019-10-31) Leme, Ala Moana [UNIFESP]; Borges, Fernanda Teixeira [UNIFESP]; http://lattes.cnpq.br/4206613998602417; http://lattes.cnpq.br/7972313651397588; Universidade Federal de São Paulo (UNIFESP)
Acute kidney injury (AKI) is characterized by the abrupt decline in glomerular filtration rate (GFR) that can be caused by sepsis, burn, hemorrhage or nephrotoxic substances such as the aminoglycoside gentamicin (Genta) antibiotic. Nephrotoxic AKI associated with these antimicrobials makes them restricted to the hospital environment. Thus, the search for treatments that prevent AKI is still necessary. Lectin extracted from the Fabaceae family plant, Dioclea violacea (DVL) is a protein of plant origin that has already had nephroprotective actions in ischemic AKI. Therefore, this study aims to evaluate the effect of DVL on gentamicin-induced acute kidney injury. Wistar rats were separated into control (CTL), Gentamicin (Genta, 40 mg/kg weight), Dioclea violacea (DVL, 0.1 mg/kg) and Gentamicin+Dioclea violacea (Genta+DVL) groups for 15 consecutive days. At the end of the experimental period, animals were weighed, 24-hour serum and urine samples collected, animal kidneys taken for creatinine analysis, proteinuria, creatinine clearance, urine sodium excretion, renal blood flow (RBF) and renal vascular resistance (RVR). Genta induced an increase in urinary volume (19,8 ± 1,77 ml), proteinuria (14,51 ± 1,73 mg/24h) and sodium (0,015 ± 0,00 %), while the Genta group + DVL (urinary volume: 14,20 ± 0,58 ml; proteinuria: 7,86 ± 0,87 mg/24h; sodium: 0,008 ± 0,00 %) did not show this increase. In renal function analysis, Genta induced increase in plasma creatinine (0,93 ± 0,09 mg/dl) compared to control ((0,58 ± 0,02 mg/dl) and this increase persisted in the Genta+DVL group 0,76 ± 0,05 mg/dl). The tubular lesion, marked by NGAL expression, showed that in the Genta group (4,3 ± 0,3 %) there was an increase compared to CTL ((0,40 ± 0,3 %) and this increase was reversed in the Genta+DVL group. (0,49 ± 0,04 %). The Genta group showed an increase in RVR ((310,21 ± 155,11 mmHg/ml) and a decrease in (RBF 5,90 ± 2,95 ml/min ml/min). However, treatment with DVL reversed both (RVR: 70,88 ± 35,44 mmHg/ml; (RBF: 22,05 ± 11,03 ml/min ml/min). For oxidative stress analysis, the Genta group showed an increase in lipid peroxidation via FOX-2 and TBARS when compared to CTL, however DVL reversed these effects. The results of this work suggest that DVL may at least partially prevent the effects of gentamicin and may be used as an aid in the prevention of nephrotoxic AKI.
Acesso aberto (Open Access)
Estudo de associação entre polimorfismos dos genes ERCC1 e ABCB1 e nefro-hepatotoxicidade à quimioterapia com Paclitaxel/Carboplatina em pacientes com câncer ginecológico
(Universidade Federal de São Paulo (UNIFESP), 2020-03-05) Costa Junior, Luiz Carlos Da [UNIFESP]; Santos, Paulo Caleb Junior De Lima [UNIFESP]; Vianna-Jorge, Rosane [UNIFESP]; http://lattes.cnpq.br/7806610722907256; http://lattes.cnpq.br/7270343730265469; http://lattes.cnpq.br/1669800539285831; Universidade Federal de São Paulo
Background: Paclitaxel/carboplatin combination is the standard chemotherapeutic protocol for gynecological cancers, but severe toxicities such as nephro and hepatotoxicity may compromise treatment. There is great interindividual variability regarding the incidence and severity of toxicities, which may be accounted to single nucleotide polymorphisms (SNPs) affecting drug transport or cellular sensitivity. Objective: To evaluate the impact of selected SNPs in ERCC1 and ABCB1 genes on the incidence of nephro- and hepatotoxicity in patients with gynecological cancer treated with paclitaxel/carboplatin. Methods: A cohort of 507 gynecological cancer patients receiving paclitaxel/carboplatin from the Brazilian National Cancer Institute (INCA-Brazil). Clinical data were obtained during routine consults or at electronic medical records. Hepatic and renal toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). Genotyping was performed using real-time PCR. Results: ABCB1 c.1236C>T was associated with moderate to severe (grades 2- 4) nephrotoxicity (OR: 2.40; 95% CI 1.39–4.15), whereas ERCC1 c.118C>T was associated with moderate to severe hepatotoxicity (OR 3.71; 95% CI 1.08– 12.77). Conclusions: ABCB1 c.1236C>T and ERCC1 c.118C>T can be potential biomarkers for the risk of nephro- and hepatotoxicity to carboplatin/paclitaxel chemotherapy of gynecological cancers.
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Ginger Essential Oil Ameliorates Cisplatin-Induced Nephrotoxicity in Mice
(Pharmacotherapy Group, 2013-12-01) Damiao, Marcio Jose [UNIFESP]; Giannocco, Gisele [UNIFESP]; Grespan, Renata; Silva, Expedito Leite; Duarte, Janaina S. [UNIFESP]; Maciel, Rui Monteiro de Barros [UNIFESP]; Yamada, Alcileia Nunes; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura; Universidade Estadual de Maringá (UEM); Universidade Federal de São Paulo (UNIFESP)
Purpose: To investigate the effect of ginger essential oil (GEO) in an experimental model of cisplatin-induced nephrotoxicity.Methods: Male mice were divided into treatment six groups (n = 7), namely: Groups I (saline), II and III (cisplatin, 10 mg/kg, i.p.) euthanized in 3th and 6th days, respectively, and IV, V and IV (GEO, 100, 200 and 400 mg/kg/day, respectively, by gavage 3, 4, 5 and 6 days after cisplatin injection). Creatinine levels and protein/creatinine ratio were determined in plasma and urine, respectively. Bone morphogenic protein (BMP-7) and tumor necrosis factor (TNF-alpha) levels of kidney tissues were determined while mRNA expression levels were obtained using real-time polymerase chain reaction.Results: GEO treatment reduced significantly creatinine levels to 0.53 +/- 0.02; 0.48 +/- 0.008 and 0.46 +/- 0.02 at 100, 200 and 400 mg/kg, respectively, compared with control (0.70 +/- 0.01) [p< 0.05] but increased protein : creatinine ratio to 0.21 +/- 0.01, 0.22 +/- 0.01, 0.24 +/- 0.02 compared with control (0.06 +/- 0.008) [p< 0.05]. Pro-inflammatory TNF-alpha mRNA expression was decreased to 1.46 +/- 0.21, 1.39 +/- 0.19 and 1.36 +/- 0.09, at GEO doses of 100, 200 and 400 mg/kg, respectively, while anti-fibrotic BMP-7 mRNA expression increased to 2.05 +/- 0.26 and 2.44 +/- 0.42 at doses of 200 and 400 mg/kg, respectively, compared with control (0.59 +/- 0.39, p < 0.05).Conclusion: GEO treatment attenuates cisplatin-induced nephrotoxicity, in part, by modulating some inflammatory cytokines.
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Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by modulating immune cell migration
(Springer, 2014-04-01) Estrela, Gabriel R. [UNIFESP]; Wasinski, Frederick [UNIFESP]; Almeida, Danilo C. [UNIFESP]; Amano, Mariane T.; Castoldi, Angela; Dias, Carolina C. [UNIFESP]; Malheiros, Denise M. A. C.; Almeida, Sandro S. [UNIFESP]; Paredes-Gamero, Edgar J. [UNIFESP]; Pesquero, Joao B. [UNIFESP]; Barros, Carlos C. [UNIFESP]; Camara, Niels O. S.; Araujo, Ronaldo C. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
Cisplatin is a chemotherapeutic agent that causes severe renal dysfunction. the kinin B1 receptor has been associated with the migration of immune cells to injured tissue as well as with renal inflammation. To examine the role of the kinin B1 receptor in cisplatin-induced acute kidney injury, we used kinin B1 receptor knockout mice and treatment with a receptor antagonist before and after cisplatin administration. Cisplatin injection caused exacerbation of renal macrophage and neutrophil migration, higher levels of serum creatinine and blood urea, upregulation of B1 receptor mRNA and an increase in pro-inflammatory cytokines expression. B1 receptor knockout mice exhibited a reduction in serum creatinine and blood urea levels, diminished apoptosis, and decreased cisplatin-induced upregulation of inflammatory components. Moreover, treatment with the B1 receptor antagonist prior to cisplatin administration normalized serum creatinine, blood urea levels, protected from acute tubular necrosis, apoptosis-related genes, and prevented upregulation of pro-inflammatory cytokines. Thus, we propose that kinins have an important role in cisplatin-induced acute kidney injury by impairing immune cells migration to renal tissue during cisplatin nephrotoxicity. Kinin B1 receptor is upregulated after cisplatin exposure.Kinin B1 receptor deficiency diminishes the nephrotoxicity caused by cisplatin.Kinin B1 receptor deficiency ameliorates the inflammatory response.Kinin B1 receptor deficiency diminishes apoptosis caused by cisplatin.Kinin B1 receptor antagonism ameliorates renal function after cisplatin injection.
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Mycophenolate Mofetil Initiation in Renal Transplant Patients at Different Times Posttransplantation: the TranCept Switch Study
(Lippincott Williams & Wilkins, 2011-05-15) Meier-Kriesche, Herwig-Ulf; Merville, Pierre; Tedesco-Silva, Helio [UNIFESP]; Heemann, Uwe; Kes, Petar; Haller, Hermann; Rostaing, Lionel; Gafner, Nesrin; Bernasconi, Corrado; Univ Florida; Hop Pellegrin; Universidade Federal de São Paulo (UNIFESP); Tech Univ Munich; Univ Hosp Ctr Zagreb; Hannover Med Sch; CHU Rangueil; Nesrin Gafner Consulting; F Hoffmann La Roche & Co Ltd
Background. Despite evidence of favorable long-term effects of mycophenolate mofetil (MMF) in renal transplantation, its introduction at different times posttransplant has not been studied in large cohorts.Methods. Single-organ renal allograft recipients (n=2217) who had MMF introduced 6 months to more than 20 years posttransplantation for various reasons were included in TranCept Switch, a multicenter, noninterventional, observational 4-year study. Changes in renal function before and after the introduction of MMF were analyzed.Results. MMF was introduced because of renal function decline in 43% of patients and poor tolerability with previous treatment in 23% of patients. the change in slope of the calculated glomerular filtration rate (modification of diet in renal diseases formula) regression line before and after MMF initiation was +2.01 mL/min per year (P<0.001) on average. the greatest benefit was noted in patients who received MMF because of renal function decline and in whom calcineurin inhibitor treatment was subsequently reduced or withdrawn (+3.09 mL/min per year). Time from transplantation to MMF introduction influenced the glomerular filtration rate at MMF initiation (slow progressive deterioration) but not the direction of the slope change, which was positive even for late introduction.Conclusion. MMF introduction may be associated with improvement or stabilization of renal function even several years after transplantation.
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Nephrotoxicity caused by brown spider venom phospholipase-D (dermonecrotic toxin) depends on catalytic activity
(Elsevier B.V., 2008-11-01) Kusma, J.; Chaim, O. M. [UNIFESP]; Wille, A. C. M.; Ferrer, V. P.; Sade, Y. B.; Donatti, L.; Gremski, W.; Mangili, O. C.; Veiga, S. S.; Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP); Univ Estadual Ponta Grossa; Catholic Univ Parana
Bites from brown spiders (Loxosceles genus) have clinical manifestations including skin necrosis with gravitational spreading, and systemic involvement that may include renal failure, hemolysis, and thrombocytopenia. Mice were exposed to recombinant wild-type phospholipase-D, or to an isoform with a mutation in the catalytic domain resulting in no phospholipasic activity. Renal biopsies from mice treated with the wild-type toxin showed glomerular edema, erythrocytes and collapse of Bowman's space, edema and deposition of proteinaceous material within the tubular lumen. Ultrastructural analyses confirmed cytotoxicity by demonstrating disorders of glomerulus at foot processes and at fenestrated endothelium. Tubule alterations include deposits of amorphous material and edema, as well as an increase of epithelial cytoplasmic multi-vesicular bodies and electron-dense structures. There was an absence of nephrotoxicity in mice treated with the mutated toxin. Analyses of urine and blood showed that wild type toxin induced hematuria and elevation of blood urea, while treatment with mutated toxin caused no changes. Mouse lethality experiments also showed oliguria and mortality after treatment with wild-type toxin, but not following exposure to the mutated toxin. Immunofluorescence using antibodies to phospholipase-D toxin showed deposition of both toxins along the renal tubular structures as detected by confocal microscopy. Immunoblots of urine showed a 30 kDa band in samples from animals treated with wild-type toxin, but no band from mice exposed to mutated toxin. Wild-type toxin treatment caused cytoplasmic vacuolization, impaired spreading, reduction of cellular viability, and cell-cell and cell-substratum detachment in MDCK cells, while treatment with mutated isoform had no effect. Finally, there is a direct correlation between toxin activity on cell membrane phospholipids generating choline and cytotoxicity. We have defined for the first time a molecular mechanism for Loxosceles venom nephrotoxicity that is dependent on the catalytic activity of phospholipase-D toxin. (c) 2008 Elsevier Masson SAS. All rights reserved.
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Nitric oxide (NO) is associated with gentamicin (GENTA) nephrotoxicity and the renal function recovery after suspension of GENTA treatment in rats
(Elsevier B.V., 2011-03-15) Christo, Joelma Santina [UNIFESP]; Rodrigues, Adelson Marçal [UNIFESP]; Mouro, Margaret Gori [UNIFESP]; Cenedeze, Marcos Antonio [UNIFESP]; Simoes, Manuel de Jesus [UNIFESP]; Schor, Nestor [UNIFESP]; Suemitsu Higa, Elisa Mieko [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
GENTA nephrotoxicity is likely to be caused, among other factors, by an increase of vasoconstrictors or a decrease of vasodilators such as NO. Few days after discontinuing GENTA treatment, the renal function is recovered, but if risk factors like advanced age, previous renal dysfunction, simultaneous use of other nephrotoxic drugs or dehydration are present, severe and progressive renal disease occurs. the aim of this study was to evaluate the renal function in rats during GENTA treatment and after its suspension as well as its relationship with NO. Rats were treated with water (vehicle, CTL) or GENTA (100 mg/kg BW) intraperitonially during 10 days; both n = 24. Twelve animals of each group were sacrificed after blood and 24 h urine were collected, and their kidneys were removed for histology. in another rats this procedure underwent after 20 or 30 days of GENTA suspension. GENTA treated group developed a marked decrease in renal function, characterized by an increased serum urea and decreased creatinine clearance; NO was increased in the serum and decreased in the urine; all P < 0.01 vs CTL. Acute tubular necrosis was confirmed in GENTA treated group. After GENTA suspension we observed a normalization of urea, creatinine clearance and serum and urinary NO; the histological lesions were also attenuated. We suggest that NO could play a role in GENTA induced nephrotoxicity and recovery. the understanding of this physiopathology could be an useful tool to prevent or blunt the nephrotoxicity progression, mainly when risk factors are present. (C) 2010 Elsevier Inc. All rights reserved.
Acesso aberto (Open Access)
Obesidade induzida após o desmame potencializa o efeito nefrotóxico da cisplatina
(Universidade Federal de São Paulo (UNIFESP), 2016-10-31) Ribeiro, Rosemara Silva [UNIFESP]; Boim, Mirian Aparecida [UNIFESP]; http://lattes.cnpq.br/8916858915652849; http://lattes.cnpq.br/6160112679243206; Universidade Federal de São Paulo (UNIFESP)
Overweight establishes a charge on the kidney resulting in increased glomerular filtration rate (GFR) and renal hypertrophy may accelerate the damage of renal function. The renal effects of obesity in adult individual are well explored, less is known on the impact of childhood obesity in the kidney in adult life, and if this event can exacerbate the renal response to an acute injury. The objectives of this study were: evaluate the impact of the obesity established in mice during childhood on renal function in adult life and evaluate if metabolic condition potentiate the nephrotoxic effects of cisplatin. C57BL/6 mice at 21 days age (postweaning) were divided into group control (CT), fed with standard diet, and high fat diet group (HF), fed with high fat diet. After 9 weeks the animals were divided into groups: CT, CT treated with cisplatin (CTCis), HF and HF treated with cisplatin (HFCis). Cisplatin was administered in single dose of 20 mg/kg (i.p.). After 72 hours the animals were anesthetized and blood and tissues (kidneys and visceral fat) were used for biochemical, molecular and histology analysis. The HF group exhibited higher body weight gain, increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration, proteinuria and intrarenal overexpression of the pro oxidant enzyme, gp91phox, indicating renal function responses to the obesity. Cisplatin induced AKI with reduced GFR in both groups, but the effect was exacerbated in obese animals with reduction of 92% versus 31% in the CTCis group, resulting in an expressive serum creatinine and urea accumulation. The HFCis group exhibited systemic and intrarenal inflammation significantly higher than the non obese animals. These results suggest that obese animals were more susceptible to the nephrotoxic effects induced by cisplatin resulting in greater severity of AKI.
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Preconditioning induced by gentamicin protects against acute kidney injury: the role of prostaglandins but not nitric oxide
(Elsevier B.V., 2011-05-15) Pessoa, Edson A. [UNIFESP]; Convento, Marcia B. [UNIFESP]; Ribas, Otoniel S. [UNIFESP]; Tristao, Vivian R. [UNIFESP]; Reis, Luciana Aparecida [UNIFESP]; Borges, Fernanda T. [UNIFESP]; Schor, Nestor [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Nephrotoxicity is the main side effect of gentamicin (GENTA). Preconditioning (PC) refers to a situation in which an organ subjected to an injury responds less intensely when exposed to another injury. the aim of this study was to evaluate the effect of PC with GENTA on nephrotoxic acute kidney injury (AKI). GENTA group rats were injected daily with GENTA (40 mg/kg/BW) for 10 days. PC animals were injected with GENTA for 3 days (40 mg/kg/BW/daily) and, after one rest week, were injected daily with GENTA for 10 days. Animals of the L-NAME and DICLO groups were preconditioned for 3 days and then received daily injections of GENTA for 10 days; they were concomitantly treated with L-NAME (10 mg/kg/BW) and diclofenac (DICLO, 5 mg/kg/BW) for 13 days. Blood and urine were collected for measurement of serum creatinine, urea, urine sodium, protein, hydroperoxides, lipid peroxidation and nitric oxide (NO). the animals were killed; kidneys were removed for histology and immunohistochemistry for apoptosis and cell proliferation. GENTA group rats showed an increase in plasma creatinine, urea, urine sodium, hydroperoxides, lipid peroxidation, proteinuria, necrosis and apoptosis, characterizing nephrotoxic AKI. PC animals showed a decrease in these parameters and increased proliferation. the blockade of NO synthesis by L-NAME potentiated the protective effect, suggesting that NO contributed to the injury caused by GENTA. the blockade of prostaglandin synthesis with DICLO increased serum and urinary parameters, blunting the protective effect of PC. Our data suggest that PC could be a useful tool to protect against nephrotoxic AKI. (C) 2011 Elsevier Inc. All rights reserved.
Restrito
The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: A scintigraphic study in rats
(Assoc Bras Divulg Cientifica, 1997-07-01) Prado, Maria José Brandão de Almeida [UNIFESP]; Nicastri, Ana Lucia; Costa, P. L. A.; Rockman, T.; Tersariol, Ivarne Luis dos Santos [UNIFESP]; Nader, Helena Bonciani [UNIFESP]; Barros, Rubens Toledo; Prado, Euthymia Brandão de Almeida; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. the chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after iv administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P<0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P<0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. the tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.
Acesso aberto (Open Access)
Uso de polimixina em pacientes submetidos a transplante: avaliação de eficácia e nefrotoxicidade
(Universidade Federal de São Paulo (UNIFESP), 2009-08-26) Mostardeiro, Marcelo Mileto [UNIFESP]; Camargo, Luis Fernando Aranha [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Introduction: Polymyxins are old antimicrobials which had their use discontinued for many years because of nephrotoxicity and neurotoxicity description. The development of multirresistant gram negative bacteria in special P aeruginosa and A baumanii all over the world is a matter of fact and we have observed its growth in international epidemiologic surveys since the 90’s. Until now we don´t have studies that demonstrate renal dysfunction tax in transplanted patients because of polymyxin use, nevertheless we know that renal function contribute in a statistical significant manner for receptors survive in long term. Methods: We have retrospectively searched for all solid organ transplanted patients and who have used polymyxins from January 2001 to December 2007 in 2 teaching hospitals in São Paulo city, Brazil. The main study objective was to define the nephrotoxicity percentage. For evaluating this variable we choosed 2 renal function definitions (first criteria and second criteria) and applied them in all studied patients with the objective of comparing them each other and with the literature. First criteria was defined as serum creatinine > 2 mg/dl after polymyxin introduction in those patients with acute renal dysfunction, or 50% serum creatinine increase in relation to value before polymyxin was given in those patients with previous nephotoxicity. In both situations described above we also considered renal dysfunction if 50% decrease in estimated creatinine clearance by Cockcroft & Gault methodology occurred, or progression to dialysis therapy. Second criteria was defined as any serum creatinine increase. Results: We identified 92 solid organ transplanted patients who used polymyxins. The majority of them received renal or renal/pancreas grafts (90.2%), and the organs transplanted were from deceased donors in 70,7%. The main site of infection were urinary tract infection (UTI) (41.3%), followed by surgical site infection (SSI) (17.4%) and pneumonia (16.3%). P aeruginosa were the main etiologic agent present in 76.1% of isolates. Microbiologic cure occurred in 25 patients (100%), clinical cure in 71 patients (77.2%), and in hospital mortality occurred in 21 patients (22.8%). Fourty four patients (47.8%) presented nephrotoxicity according to any of the 2 adopted criteria, 30 patients (32.6%) according to the first criteria, and 44 patients (47.8%) according to the second criteria. Multivariate analysis show statistical significant association among UTI and protection for renal dysfunction [p 0.02; OR 0.24; IC 95% (0.07 – 0.86)], and greater mean polymyxin utilization time (p 0.03) as a risk factor for renal dysfunction by the first criteria. Conclusions: The 32.6% percentage of renal dysfunction is still high, but lower than that reported in the 60’s and 70’s. Polymyxin utilization is effective principally for the treatment of UTI in solid organ transplanted patients, its use should be judicious and for shorter time as possible.

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