Erythropoietin Attenuates Apoptosis After Ischemia-Reperfusion-Induced Renal Injury in Transiently Hyperglycemic Wister Rats

Background. Hyperglycemia is associated with a decreased tolerance to ischemia and an increased severity of renal ischemia reperfusion (I/R) injury. It has been suggested that erythropoietin (EPO) attenuates this effect in normoglycemic animals. This study sought to examine the effects of EPO on treatment renal I/R injury (IRI) in transiently hyperglycemic rats.Material and Methods. Twenty-eight male Wister rats anesthetized with isoflurane received glucose (2.5 g.kg(-1) intraperitoneally) before right nephrectomy. They were randomly assigned to four groups: sham operation (S); IRI (ISO); IRI+EPO, (600 UI kg(-1) low-dose EPO [EL]); and IRI+EPO 5000 UI kg(-1) (high-dose EPO [EH]). IRI was induced by a 25-minute period of left renal ischemia followed by reperfusion for 24 hours. Serum Creatinine and glucose levels were measure at baseline (M1), immediately after the ischemic period (M2), and at 24 hours after reperfusion (M3). After sacrificing the animals, left kidney specimens were submitted for histological analysis including flow cytometry to estimate tubular necrosis and the percentages of apoptotic, dead or intact cells.Results. Scr in the ISO group was significantly higher at M3 than among the other groups. Percentages of early apoptotic cells in ISO group were significantly higher than the other groups. Percentages of late apoptotic cells in S and ISO groups were significantly greater than EL and EH groups. However, no significant intergroup differences were observed regarding the incidence of tubular necrosis.Conclusions. Our results suggested that, although not preventing the occurrence of tubular necrosis, EPO attenuated apoptosis and glomerular functional impairment among transiently hyperglycemic rats undergoing an ischemia/reperfusion insult.

Tratamento da síndrome do roubo devido a fístula arteriovenosa para hemodiálise em membro inferior por meio da técnica de ligadura arterial e revascularização distal (técnica de DRIL)

RESUMO A fístula arteriovenosa com bom fluxo sangüíneo é de fundamental importância para os pacientes portadores de insuficiência renal crônica em tratamento hemodialítico. Uma das complicações da fístula arteriovenosa é a síndrome do roubo, mas esta é de ocorrência incomum, e o seu tratamento está diretamente indicado quando há sintomas manifestos. Vários métodos foram propostos para sua correção nos membros superiores, sendo considerada a revascularização distal com ligadura arterial o procedimento de escolha. Neste relato de caso inédito, descreve-se o tratamento da síndrome do roubo de uma fístula arteriovenosa realizada em membro inferior, tratada com sucesso por meio da mesma técnica indicada para os membros superiores.

Fatores de risco para mortalidade na lesão renal aguda

OBJETIVO: Este trabalho tem como objetivo avaliar a evolução de pacientes com lesão renal aguda (LRA) por Necrose Tubular Aguda internados no Hospital das Clínicas da Faculdade de Medicina de Botucatu - UNESP. MÉTODOS: Trata-se de estudo de coorte retrospectivo, no qual foram avaliados 477 pacientes maiores de 18 anos, no período de janeiro de 2001 a dezembro de 2008. LRA foi definida de acordo com os valores de creatinina sérica, conforme proposto pelo Acute Kidney Injury Network (AKIN). RESULTADOS: A média de idade da população estudada foi de 65,5 ± 16,2 anos, com predomínio de homens (62%) e com idade > 60 anos (65,2%). Diabetes mellitus ocorreu em 61,9%, hipertensão arterial em 44,4% e doença renal crônica em 21,9%. A mortalidade foi de 66%. Após análise multivariada, foram variáveis associadas ao óbito a necessidade de diálise, internação em UTI, idade > 60 anos e menor tempo de acompanhamento nefrológico. A recuperação renal entre os sobreviventes foi de 96,9%. CONCLUSÃO: Este trabalho mostra que a evolução dos pacientes com LRA provenientes de enfermarias clínica e cirúrgica é semelhante à literatura. Porém, a alta mortalidade do grupo mostra a necessidade da identificação de fatores de risco para o desenvolvimento de LRA nesses pacientes e capacitação da equipe assistente para o diagnóstico precoce dessa síndrome.

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)

Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats

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

Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats

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

Influence of tetracycline in the hepatic and renal development of rat's offspring

O objetivo deste estudo foi avaliar os possíveis efeitos da tetraciclina administrada a ratas, no décimo dia de gestação, no desenvolvimento hepático e renal de seus filhotes. O fígado mostrou vacuolização, necrose, inflamação e dilatação sinusoidal mais evidente em recém-nascidos. Mitoses, aumento precoce da população de células de Kupffer e hipertrofia de hepatócitos com maior síntese de glicogênio estavam presentes no décimo e vigésimo dias de vida. O rim mostrou vacuolização tubular e necrose discretas, mais evidentes nos recém-nascidos, assim como sinais de regeneração tubular no décimo e vigésimo dias. Esses resultados sugeriram que os órgãos estudados sofreram alterações morfológicas transitórias durante o desenvolvimento, mas apresentaram sinais de regeneração ao longo dos primeiros dias de vida.

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.

Efeitos da correção da acidose metabólica com bicarbonato de sódio sobre o catabolismo protéico na insuficiência renal crônica

A desnutrição protéico-energética constitui problema comum aos pacientes com insuficiência renal crônica, influenciando diretamente na sua morbi-mortalidade. A acidose metabólica tem papel no catabolismo protéico, ativando a via proteolítica proteasoma-ubiquitina, dependente de adenosina trifosfato, e conjuntamente com glicocorticóides induz uma maior atividade na desidrogenase que degrada os aminoácidos de cadeia ramificada. Esta revisão teve como objetivo descrever o mecanismo pelo qual a acidose metabólica nos pacientes com insuficiência renal crônica promove o catabolismo protéico, favorecendo assim a desnutrição, bem como avaliar os efeitos do uso de bicarbonato de sódio na correção da acidose e conseqüentemente redução do catabolismo protéico. Pesquisas mostram melhora da acidose pelo uso de bicarbonato de sódio e conseqüente redução do catabolismo protéico na insuficiência renal crônica, podendo ser esta uma conduta promissora na atenuação da desnutrição nestes pacientes.

Effect of uroguanylin on potassium and bicarbonate transport in rat renal tubules

The effect of uroguanylin (UGN) oil K(+) and H(+) secretion in the renal tubules of the rat kidney was studied using in vivo stationary microperfusion. For the study of K(+) secretion, a tubule was Punctured to inject a column of FDC-green-colored Ringer's solution with 0.5 mmol KCI/L 10(-6)(mol UGN/L, and oil was Used to block fluid flow. K(+) activity and transepithelial potential differences (PD) were measured with double microelectrodes (K(+) ion-selective resin vs. reference) in the distal tubules of the same nephron. During perfusion, K(+) activity rose exponentially, from 0.5 mmol/L to stationary concentration, allowing for the calculation of K(+) secretion J(K)). JK increased from 0.63 +/- 0.06 nmol.cm(-2).s(-1) in the control croup to 0.85 +/- 0.06 in the UGN group (p < 0.01). PD was -51.0 +/- 5.3 mV in the control group and -50.3 +/- 4.98 mV in the UGN group. In the presence of 10(-7) mol iberiotoxin/L, the UGN effect was abolished: JK was 0.37 +/- 0.038 nmol-cm(-2).s(-1) in the absence of, and 0.38 +/- 0.025 in the presence of, UGN. indicating its action oil rnaxi-K channels. In another series of experiments, renal tubule acidification was studied, using similar method: proximal and distal tubules were perfused with solutions containing 25 mmol NaHCO(3)/L. Acidification half-time was increased both in proximal and distal segments and, as a consequence, bicarbonate reabsorption decreased in the presence of UGN (in proximal tubules, from 2.40 +/- 0.26 to 1.56 +/- 0.21 nmol-cm(-2).s(-1)). When the Na(+)/H(+) exchanger was inhibited by 10(-4) mol hexamethylene amiloride (HMA)/L, the control and UGN groups were not significantly different. In the late distal tubule, after HMA, UGN significantly reduced J(HCO3)(-). indicating all effect of UGN oil H(+)-ATPase. These data show that UGN stimulated J(K)(+) by actin, oil maxi-K channels. and decreased J(HCO3)(-) by acting on NHE3 in proximal and H(+)-ATPase in distal tubules.

Acute renal failure: Clinical outcome and causes of death

Acute renal failure (ARF) is a frequent complication in hospitalized patients and is strongly related to increase in mortality. In order to analyze the clinical outcome and the prognostic factors in hospital-acquired ARF a prospective study was performed. Data from 200 patients with established ARF during the period of January 1987 through July 1990 were collected. The incidence of ARF was 4.9/1000 admissions. Renal ischemia (50%) and nephrotoxic drugs (21%) were the main etiologic factors. The histologic study done in 43 patients showed: acute tubular necrosis (53%), tubular hydropic degeneration (16%), glomerulopathies (16%), and other lesions (15%). Dialysis therapy was performed in 101 patients. The mortality rate was 46.5% and the most important causes of death were. sepsis (38%), respiratory failure (19%), and multiple organ failure (11%). Higher mortality was observed in oliguric patients (62.9%) than nonoliguric (34.5%) (p < 0.05) and in ischemic renal failure (56.7%) when compared to nephrotoxic renal failure (14.7%) (p < 0.05). As primary cause of death was not associated to the acute renal failure, conclude that acute renal failure is an important marker of the gravity of the underlying disease and not the cause of death.

RENAL EXCRETION OF ZINC IN NORMAL INDIVIDUALS DURING ZINC TOLERANCE-TEST AND GLUCOSE-TOLERANCE TEST

The urinary excretion, renal clearance, and tubular reabsorption of zinc were investigated in 30 adult healthy subjects under basal conditions and during the zinc and glucose tolerance tests. After a 12h overnight fast, each subject was submitted to renal clearance of zinc. The procedures were performed between 8.00 and 12.00 a.m., after emptying the bladder and ingestion of 4 ml deionized water/kg body weight at 8.00 a.m. The first urine sample was collected at 10.00 a.m., and the second at 12.00 a.m. A dose of 110 mg ZnSO4.7H(2)O was administered orally to each subject, diluted in 20 mi deionized water, at time 0 min. Blood samples were collected from an antecubital vein at times -30, 0, and 30 min and at 30 min intervals up to 240 min. Glucose was administered intravenously (0.5 ml 50%/kg body weight) during the first 3 min of the test, and blood samples were collected from an unconstricted, contralateral, antecubital vein at times -30, 0, 3, 5, 10, 20, 30, 45, 60, and 90 min. The results showed that urinary zinc excretion, and renal zinc clearance were significantly higher during the zinc and glucose tolerance tests than in the control condition. on the other hand, renal zinc clearance was more elevated during the glucose tolerance test than during the zinc tolerance test. Variations in zinc tubular reabsorption and glomerular filtration rate were not detected. The results suggest that urinary excretion and renal clearance of zinc in healthy subjects increase during acute zinc ingestion and glucose infusion. Although zinc ingestion raised urinary zinc excretion, glucose infusion was more effective in increasing renal zinc clearance. These normal parameters are important in the investigation of diabetic patients with serum and urine zinc changes.

Effect of renoguanylin on hydrogen/bicarbonate ion transport in rat renal tubules

Renoguanylin (REN) is a recently described member of the guanylin family, which was first isolated from eels and is expressed in intestinal and specially kidney tissues. In the present work we evaluate the effects of REN on the mechanisms of hydrogen transport in rat renal tubules by the stationary microperfusion method. We evaluated the effect of 1 mu M and 10 mu M of renoguanylin (REN) on the reabsorption of bicarbonate in proximal and distal segments and found that there was a significant reduction in bicarbonate reabsorption. In proximal segments, REN promoted a significant effect at both 1 and 10 mu M concentrations. Comparing control and REN concentration of 1 mu M, JHCO(3)(-) . nmol cm(-2) s(-1) -1,76 +/- 0.11(control) x 1,29 +/- 0,08(REN) 10 mu m: P<0.05, was obtained. In distal segments the effect of both concentrations of REN was also effective, being significant e.g. at a concentration of 1 mu M (JHCO(3)(-), nmol cm(-2) s(-1) -0.80 +/- 0.07(control) x 0.60 +/- 0.06(REN) 1 mu m; P<0.05), although at a lower level than in the proximal tubule. Our results suggest that the action of REN on hydrogen transport involves the inhibition of Na(+)/H(+) exchanger and H(+)-ATPase in the luminal membrane of the perfused tubules by a PKG dependent pathway. (c) 2009 Elsevier B.V. All rights reserved.

Renal excretion of zinc in normal individuals during zinc tolerance test and glucose tolerance test

The urinary excretion, renal clearance, and tubular reabsorption of zinc were investigated in 30 adult healthy subjects under basal conditions and during the zinc and glucose tolerance tests. After a 12h overnight fast, each subject was submitted to renal clearance of zinc. The procedures were performed between 8.00 and 12.00 a.m., after emptying the bladder and ingestion of 4 ml deionized water/kg body weight at 8.00 a.m. The first urine sample was collected at 10.00 a.m., and the second at 12.00 a.m. A dose of 110 mg ZnSO47H2O was administered orally to each subject, diluted in 20 ml deionized water, at time 0 min. Blood samples were collected from an antecubital vein at times -30, 0, and 30 min and at 30 min intervals up to 240 min. Glucose was administered intravenously (0.5 ml 50%/kg body weight) during the first 3 min of the test, and blood samples were collected from an unconstricted, contralateral, antecubital vein at times -30, 0, 3, 5, 10, 20, 30, 45, 60, and 90 min. The results showed that urinary zinc excretion, and renal zinc clearance were significantly higher during the zinc and glucose tolerance tests than in the control condition. On the other hand, renal zinc clearance was more elevated during tile glucose tolerance test than during the zinc tolerance test. Variations in zinc tubular reabsorption and glomerular filtration rate were not detected. The results suggest that urinary excretion and renal clearance of zinc in healthy subjects increase during acute zinc ingestion and glucose infusion, Although zinc ingestion raised urinary zinc excretion, glucose infusion was more effective in increasing renal zinc clearance. These normal parameters are important in the investigation of diabetic patients with serum and urine zinc changes.

Insuficiência renal aguda. Estudo do quadro clínico e prognóstico.

Acute renal failure (ARF) is a frequent complication in hospitalized patients, and is strongly related to increase of mortality. PURPOSE: To analyze the clinical outcome and the prognostic factors in hospital acquired AFR. METHOD: A prospective study was performed. Data from 200 patients with established ARF admitted during the period of January, 1987 and July, 1990 were collected. RESULTS: The incidence of ARF was 4.9/1000 admissions. Renal ischemia (50%) and nephrotoxic drugs (21%) were the main etiologic factors. The histologic study done in 43 patients showed: acute tubular necrosis (53%), tubular hydrophic degeneration (16%), glomerulopathies (16%) and other lesions (15%). Dialysis therapy was performed in 101 patients and the main indications were: uremia (67%), hypervolemia (22%) and hyperkalemia (9%). The mortality rate was 46.5% and the most important causes of death were: sepsis (38%), respiratory failure (19%) and multiple organs failure (11%). Treatment withdraw was the cause of death in 2 patients. Higher mortality was observed in oliguric patients (62.9%) than non-oliguric (34.5%) (p < 0.05) and in ischemic renal failure (56.7%) when compared to nephrotoxic renal failure (14.7%) (p < 0.05). This difference was maintained when the comparison was done only between dialyzed patients. CONCLUSION: As primary cause of death was not associated to the acute renal failure, we conclude that acute renal failure is an important marker of the gravity of the underlying disease and not the cause of death.