Eficácia da solução de cloreto de sódio a 7,5% com e sem dextran 70 a 6% na preservação da função renal de cães hipovolêmicos submetidos à isquemia-reperfusão

JUSTIFICATIVA E OBJETIVOS: As soluções hipertônicas de cloreto de sódio, associadas ou não a colóides hiperoncóticos, podem ser eficazes em proteger o rim em situações de hipovolemia. O objetivo deste estudo foi verificar, em cães, o real benefício dessas soluções sobre a função renal, em vigência de hipovolemia e isquemia do órgão. MÉTODO: em 24 cães, anestesiados com pentobarbital sódico, submetidos à nefrectomia direita e à expansão volêmica com solução de Ringer (1 ml.kg-1.min-1), foram observadas possíveis alterações renais morfo-funcionais após hemorragia de 20 ml.kg-1 e trinta minutos de total isquemia renal esquerda, com posterior reperfusão, além da repercussão renal da administração de soluções de cloreto de sódio 7,5% (SH) e esta em dextran 70 a 6% (SHD). Atributos estudados: FC, PAM, pressão de veia cava inferior, fluxo sangüíneo renal, resistência vascular renal, hematócrito, Na+, K+, osmolaridade plasmática, PaO2, PaCO2 e pH, depuração (para-aminohipurato de sódio - PAH-1, creatinina, osmolar, água livre, Na+, K+), fração de filtração, volume e osmolaridade urinários, excreções urinárias e fracionárias de Na+ e K+ e exame histopatológico do rim. Os atributos foram estudados em três grupos (G1, G2 e G3) e em cinco momentos. RESULTADOS: Houve elevação estatisticamente significativa da pressão arterial média em G2 e G3, da resistência vascular renal em G1, do fluxo sangüíneo renal e da depuração de PAH em G3, da excreção fracionária de Na+ em G2 e G3, das depurações de creatinina, osmolar, de água livre e de Na+ e K+, da excreção urinária de Na+ e K+ e do volume urinário em G3. CONCLUSÕES: A SHD administrada 15 minutos após hemorragia moderada e 30 minutos antes de insulto isquêmico de 30 minutos foi eficiente em proteger o rim de cães das repercussões da isquemia-reperfusão. Não foi constatada alteração histopatológica renal à microscopia óptica.

Advances in Peritoneal Dialysis in Acute Kidney Injury

Peritoneal dialysis (PD) is a simple, safe, cheap, and efficient renal replacement therapy method. It can correct metabolic disorders and fluid overload in acute kidney injury (AKI) patients both in and out of the intensive care unit. Use of PD in AKI is enhanced by placement of a Tenckhoff catheter, which can be safely accomplished at the bedside. Some PD modalities, such as high-volume PD and continuous-flow PD, can provide dialysis doses and efficiency comparable to extracorporeal blood purification methods. PD is particularly suitable for neonates, children, and patients with refractory heart failure or who are otherwise hemodynamically unstable. PD should be considered in situations where systemic anticoagulation and/or vascular access are problematic. PD is limited by a lower efficiency that may produce inadequate renal replacement in larger and/or severely hypercatabolic patients. Fluid removal can be unpredictable, there is a risk of infection, and possible issues with mechanical ventilation. In this article, we discuss the use of PD in AKI, with emphasis on recent advances. Copyright (c) 2012 S. Karger AG, Basel

Desenvolvimento de um modelo experimental de hemodiálise em cães

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

Interaction of the Anti-Inflammatory Annexin A1 Protein and Tacrolimus Immunosuppressant in the Renal Function of Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Renal function and histology after acute hemorrhage in rats under dexmedetomidine action

OBJETIVO: Cerca de 50% de indicações de diálise em insuficiência renal aguda vêm de problemas do perioperatório. Alterações na hemodinâmica intra-operatória levam a vasoconstrição renal e hipoperfusão. Estudos prévios não definiram o papel renal da dexmedetomidina em hemorragia. Foram estudados os efeitos da dexmedetomidina na função e histologia renais, em ratos, após hemorragia aguda. MÉTODOS: Estudo encoberto com 20 ratos Wistar, anestesiados com pentobarbital sódico intraperitoneal, 50 mg. kg-1, divididos aleatoriamente em 2 grupos sob sangramento de 30% da volemia: GD - dexmedetomidina iv, 3 µg. kg-1 (10 min), e infusão contínua, 3 µg. kg-1. h-1; GC - pentobarbital. Para estimar depuração renal, administraram-se para-aminohipurato e iotalamato de sódio. Atributos estudados: freqüência cardíaca, pressão arterial média, temperatura retal, hematócrito, depuração de para-aminohipurato e iotalamato, fração de filtração, fluxo sangüíneo renal, resistência vascular renal, análise histológica dos rins. RESULTADOS: em GD, houve valores menores de freqüência cardíaca, pressão arterial média e resistência vascular, mas valores maiores de depuração de iotalamato e fração de filtração. A depuração de para-aminohipurato e o fluxo sangüíneo foram similares nos grupos. As alterações histológicas foram compatíveis com isquemia e houve maior dilatação tubular em GD. CONCLUSÃO: em ratos, após hemorragia aguda, a dexmedetomidina determinou melhor função renal, porém maior dilatação tubular.

Utilization of peritoneal dialysis in the acute setting

Peritoneal dialysis (PD), although classically described and utilized in the treatment of patients with end-stage renal disease, can also be utilized in the acute setting in different clinical situations. Recent studies showed that, in patients with acute renal failure, it is possible to obtain reasonable dialysis doses with adequate metabolic and etectrolytic control and tow incidence of complications by utilizing continuous PD through a cycler at high volume. In patients with congestive heart failure without end-stage renal disease, PD is capable of promoting clinical improvement with slow removal of liquids, becoming an attractive alternative for situations of rapidly or slowly worsening cardiac function. In patients submitted to chronic hemodialysis but who have vascular access difficulties, PD can also be utilized as a bridge, thereby avoiding the use of central venous catheters, which can be associated with infectious complications such as bacterial endocarditis. New studies must be realized showing other indications for PD.

CHANGES IN VASCULAR-RESISTANCE DURING CAROTID OCCLUSION IN NORMAL AND BARORECEPTOR-DENERVATED RATS

In the present study, we investigated changes in mesenteric, renal, and hindquarter vascular resistance during the pressor response produced by bilateral carotid occlusion (BCO) in conscious, freely moving normal and denervated (aortic, carotid, or both) rats. BCO was performed using special previously implanted cuffs. In control normal rats, the increase in mean arterial pressure (MAP) during early and late responses (37 +/- 4 and 21 +/- 2 mm Hg, respectively) was related to increased renal (125 +/- 12% and 45 +/- 10%) and mesenteric (38 +/- 13% and 41 +/- 5%) but not hindquarter (14 +/- 4% and 8 +/- 7%) vascular resistance. In aortic-denervated rats, the greater MAP increase in early and late responses (57 +/- 4 and 44 +/- 4 mm Hg, respectively) compared with normal rats was related to a marked increase in hindquarter (137 +/- 26% and 106 +/- 26%) and mesenteric (104 +/- 14% and 66 +/- 9%) vascular resistance. In carotid-denervated rats, MAP increase and change in vascular resistance were similar to those values observed in control rats. Sinoaortic-denervated rats showed a greater MAP increase (34 +/- 4 mm Hg) during late response and a reduced increase in renal vascular resistance (46 +/- 6%) during early response. The present results show that 1) the pressor response to BCO in normal rats is associated with an increase in renal and mesenteric vascular resistance, 2) the aortic baroreceptors buffer the increase in mesenteric and especially hindquarter vascular resistance during BCO, and 3) the reduced pressor response in late response is probably related to a reduced increase in renal vascular resistance during this component compared with the early response.

A2 Noradrenergic Lesions Prevent Renal Sympathoinhibition Induced by Hypernatremia in Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

EFEITOS DA INFUSAO CONTINUA DO PROPOFOL SOBRE A FUNCAO RENAL DO CAO. ESTUDO COMPARATIVO COM O PENTOBARBITAL SODICO

Little research has been done with propofol in relation to renal function. The aim of this study was to evaluate the effects of the continuous infusion of propofol on renal function in dogs. Sixteen dogs, previously anesthetized with pentobarbital sodium (30 mg.kg-1) for surgical preparation, catheterism and monitoring, were studied. The dogs were mechanically ventilated with air and received alcuronium (0.2 mg.kg-1 in bolus and 0.06 mg.kg-1 - maintenance). The following parameters were studied: heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), aortic blood flow (A(o)BF - by electromagnetic flowmeter installed in the ascending aortic), aortic vascular resistance index (A(o)VRI), renal plasma flow (ERPF - by para-aminohipurate clearance), glomerular filtration rate (GFR - by creatinine clearance), effective renal blood flow (ERBF = ERPF/1 - hematocrit), urinary volume (UV), renal vascular resistance (RVR = MAP.80/ERBF.10-3), urinary sodium excretion (UE(Na)), fractionated sodium excretion (FE(Na)), osmolar clearance (C(osm)) and free water clearance (C(H2O)). These parameters were studied at 15 (M1), 30 (M2), 45 (M3) and 60 (M4) min after beginning pentobarbital sodium infusion (5 mg.kg-1.h-1). The dogs were allocated into two groups of eight animals each: G1 (control-pentobarbital sodium) and G2 (propofol). In G1, pentobarbital was given at the four times studied. G2 dogs received the same treatment as G1 dogs at M1 and M2; infusion of pentobarbital was substituted by propofol (3 mg.kg-1 bolus, followed by 12 mg.kg-1.h-1 continuous infusion) at M3 and M4. Profile Analysis was used to analyze the results statistically. In G1 (pentobarbital), there was a significant increase in RVR (M1 < M4) and a decrease in ERPF and ERBF (M1 > M4). In G2 (propofol) there was only a significant increase in A(o)BF (M1 < M2 = M3). In comparison among groups, these was a significant alteration of FE(Na) at M3 (pentobarbital > propofol). It was observed that the continuous infusion of propofol in dogs, at the given doses, did not alter the basic variables of renal function and hemodynamics studied. We concluded that propofol can be one of the drugs of choice to provide base anesthesia in studies of renal function in dogs.

EFEITOS DO SULFATE DE MAGNESIO NA HEMODINAMICA E FUNCAO RENAL DE CAES ANESTESIADOS CORN PENTOBARBITAL SODICO

Background and objectives - The use of magnesium sulphate for the prevention of seizures in pre-eclampsia may induce hypermagnesemia. Clinical and experimental studies are not in agreement about the effects of magnesium on the renal hemodynamics and function. We therefore studied the effects of hypermagnesemia on the renal hemodynamics and function of dogs anesthetized with pentobarbitone. Methods - Sixteen mongrel dogs were anesthetized with pentobarbitone 30 mg.kg-1 and submitted to extracellular ) and mechanical ventilation with room air. The dogs were volume expansion with Ringer's solution (0.4 ml.kg.min allocated into two groups of 8 animals, for the study of renal hemodynamics and function following the administration of 5 mg.kg-1 of pentobarbitone (Group 1 - control or of pentobarbitone associated with magnesium sulphate in the dose (Group 2). The parameters studied were: PAH of 140 mg.kg, administered in 15 minutes, followed by 80 mg.kg-1.h-1 clearance, creatinine clearance, osmolar clearance, free water clearance, renal blood flow, renal vascular resistance, filtration fraction, urinary volume, plasmatic and urinary osmolarity, urinary and fractionary excretion of sodium and potassium, measured at five moments: 15 (M1), 30 (M2), 60 (M3) and 75 (M4) minutes after the first supplementary dose of pentobarbitone and 15 minutes (M5) after the second supplementary dose in Group 1. In Group 2, the moments M3, M4, M5 were 15, 30 and 60 minutes after the priming dose of magnesium sulphate and during the maintenance dose. Results - In Group I no significant changes were observed in renal hemodynamic parameters and creatinine clearance. The extracellular volume expansion increased urinary volume and decreased urinary osmolarity as a consequence of sodium, potassium and free water clearance. The fractionary excretion of sodium was maintained. The plasmatic osmolarity increased. In Group 2, renal hemodynamic parameters and creatinine clearance were also maintained. There was an increase in renal sodium clearance, as detected by the increase in the fractionary excretion of sodium. Conclusions - Magnesium sulphate did not produce significant changes in renal hemodynamics and facilitated the renal excretion of sodium in dogs anesthetized with pentobarbitone.

Action of anti-bothropic factor isolated from Didelphis marsupialis on renal effects of Bothrops erythromelas venom

Acute renal failure is the most common complication in the lethal cases caused by snakebites in Brazil. Among the Brazilian venom snakes, Bothrops erythromelas is responsible for the majority of accidents in Northeastern Brazil. Didelphis marsupialis serum could inhibit myonecrotic, hemorrhagic, edematogenic hyperalgesic and lethal effects of envenomation determined by ophidian bites. In the present study, we evaluated the action of the anti-bothropic factor isolated from D. marsupialis on the renal effects promoted by B. erythromelas venom without systemic interference. Isolated kidneys from Wistar rats were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. We analyzed renal perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), and the percentages of sodium and potassium tubular transport (%TNa +, %TK +). The B. erythromelas venom (10 μg mL -1) decreased the PP (ct=108.71±5.09 mmHg; BE=65.21±5.6 mmHg*) and RVR (ct=5.76±0.65 mmHg mL -1 g -1 min -1; BE=3.10±0.45 mmHg mL -1 g -1 min -1*) . On the other hand, the GFR decreased at 60 min (ct 60=0.76±0. 07 mL g -1 min -1; BE 60=0.42±0.12 mL g -1 min -1*) and increased at 120 min (ct 120=0.72±0.01 mL g -1 min -1; BE 120=1.24±0.26 mL g -1 min -1*). The UF increased significantly when compared with the control group (ct=0.14±0.01 mL g -1 min -1; BE=0.47±0.08 mL g -1 min -1*). The venom reduced the %TNa + (ct 90=79.18±0.88%; BE 90=58.35±4.86%*) and %TK + (ct 90=67.20±4.04%; BE 90=57. 32±5.26%*) The anti-bothropic factor from D. marsupialis (10 μg mL -1) incubated with B. erythromelas venom (10 μg mL -1) blocked the effects on PP, RVR, %TNa +, and %TK +, but was not able to reverse the effects in UF and GFR promoted by venom alone. However, the highest concentration of D. marsupialis serum (30 μg mL -1) reversed all the renal effects induced by the venom. In conclusion, B. erythromelas venom altered all the renal functional parameters evaluated and the anti-bothropic factor from D. marsupialis was able to inhibit the effects induced by the venom in isolated kidney. © 2005 Elsevier Ltd. All rights reserved.

Could albumin level explain the higher mortality in hemodialysis patients with pulmonary hypertension?

Background: The pathogenesis of pulmonary hypertension (PH) in hemodialysis is still unclear. The aim of thisstudy was to identify the risk factors associated with the presence of PH in chronic hemodialysis patients and toverify whether these factors might explain the highest mortality among them.Methods: We conducted a retrospective study of hemodialysis patients who started treatment from August 2001to October 2007 and were followed up until April 2011 in a Brazilian referral medical school. According to theresults of echocardiography examination, patients were allocated in two groups: those with PH and those withoutPH. Clinical parameters, site and type of vascular access, bioimpedance, and laboratorial findings were comparedbetween the groups and a logistic regression model was elaborated. Actuarial survival curves were constructed andhazard risk to death was evaluated by Cox regression analysis.Results: PH > 35 mmHg was found in 23 (30.6%) of the 75 patients studied. The groups differed in extracellularwater, ventricular thickness, left atrium diameter, and ventricular filling. In a univariate analysis, extracellular waterwas associated with PH (relative risk = 1.194; 95% CI of 1.006 1.416; p = 0.042); nevertheless, in a multiple model,only left atrium enlargement was independently associated with PH (relative risk =1.172; 95% CI of 1.010 1.359;p = 0.036). PH (hazard risk = 3.008; 95% CI of 1.285 7.043; p = 0.011) and age (hazard risk of 1.034 per year of age;95% CI of 1.000 7.068; p = 0.047) were significantly associated with mortality in a multiple Cox regression analysis.However, when albumin was taken in account the only statistically significant association was between albuminlevel and mortality (hazard risk = 0.342 per g/dL; 95% CI of 0.119 0.984; p = 0.047) while the presence of PH lost itsstatistical significance (p = 0.184). Mortality was higher in patients with PH (47.8% vs 25%) who also had astatistically worse survival after the sixth year of follow up.Conclusions: PH in hemodialysis patients is associated with parameters of volume overload that sheds light on itspathophysiology. Mortality is higher in hemodialysis patients with PH and the low albumin level can explain thisassociation.© 2012 Greenfield et al.; licensee BioMed Central Ltd.

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.

Efeitos determinados pelo pneumoperitônio sobre a hemodinâmica e função renais de cães ventilados com volume e pressão controlados

Pós-graduação em Anestesiologia - FMB

Desenvolvimento de um modelo experimental de hemodiálise em cães

Com o objetivo de desenvolver um modelo de hemodiálise (HD) em cães, foram estudados 18 animais, sem raça definida, machos, clinicamente sadios, com peso corporal variando entre sete e 14 kg. O acesso vascular foi obtido através de implantação do cateter de duplo lúmen em veia jugular externa. As sessões de HD, em número de cinco por animal, com até três horas de duração, foram realizadas em hemodialisadora de sistema proporcional com ultrafiltração (UF) controlada, com solução dialisante padrão e tampão bicarbonato. A UF foi ajustada para HD isovolêmica, utilizou-se perfil de sódio, e para anticoagulação heparina sódica. Os animais foram mantidos anestesiados com cloridrato de levomepromazina e propofol. Foram avaliados dados hematológicos, bioquímicos, hemogasometria, pressão arterial sistêmica e tempo de coagulação ativado. Foi observada diminuição do número global de hemácias, volume globular, hemoglobina e leucócitos. Em relação aos exames bioquímicos, houve manutenção nos níveis de sódio sérico, e quanto à hemogasometria, a manutenção da SO₂. A pressão arterial sistêmica manteve-se constante. Os resultados obtidos no presente trabalho permitiram concluir que foi possível o desenvolvimento do modelo proposto e mostrou que a HD em cães é um método viável e seguro, que poderá contribuir para o tratamento clínico da insuficiência renal nesta espécie.