Effects of high glucose concentrations on the endothelial function of the renal microcirculation of rabbits

OBJECTIVE: To assess the acute effects of high glucose concentrations on vascular reactivity in the isolated non diabetic rabbit kidney. METHODS: Rabbits were anaesthetized for isolation of the kidneys. Renal arteries and veins were cannulated for perfusion with Krebs-Henselleit solution and measurement of perfusion pressure. After 3 hours of perfusion with glucose 5,5 mM (control ) and 15 mM, the circulation was submitted to sub maximal precontraction (80% of maximal response) trough continuous infusion of noradrenaline 10 mM. Vascular reactivity was then assessed trough dose-responses curves with endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators. The influence of hyperosmolarity was analyzed with perfusion with mannitol 15mM. RESULTS: A significant reduction in the endothelium-dependent vasodilation in glucose 15mM group was observed compared to that in control, but there was no difference in endothelium-independent vasodilation. After perfusion with mannitol 15 mM, a less expressive reduction in endothelium-dependent vasodilation was observed, only reaching significance in regard to the greatest dose of acetylcholine. CONCLUSION: High levels of glucose similar to those found in diabetic patients in the postprandial period can cause significant acute changes in renal vascular reactivity rabbits. In diabetic patients these effects may also occur and contribute to diabetes vascular disease.

Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow

This study was undertaken in anesthetized dogs to evaluate the relative participation of prostaglandins (PGs) and nitric oxide (NO) in the maintenance of total renal blood flow (TRBF), and renal medullary blood flow (RMBF). It was hypothesized that the inhibition of NO should impair cortical and medullary circulation because of the synthesis of this compound in the endothelial cells of these two territories. In contrast, under normal conditions of perfusion pressure PG synthesis is confined to the renal medulla. Hence PG inhibition should predominantly impair the medullary circulation. The initial administration of 25 µM kg-1 min-1 NG-nitro-L-arginine methyl ester produced a significant 26% decrease in TRBF and a concomitant 34% fall in RMBF, while the subsequent inhibition of PGs with 5 mg/kg meclofenamate further reduced TRBF by 33% and RMBF by 89%. In contrast, the initial administration of meclofenamate failed to change TRBF, while decreasing RMBF by 49%. The subsequent blockade of NO decreased TRBF by 35% without further altering RMBF. These results indicate that initial PG synthesis inhibition predominantly alters the medullary circulation, whereas NO inhibition decreases both cortical and medullary flow. This latter change induced by NO renders cortical and RMBF susceptible to a further decrease by PG inhibition. However, the decrease in medullary circulation produced by NO inhibition is not further enhanced by subsequent PG inhibition.

Circulating forms of parathyroid hormone detected with an immunofluorometric assay in patients with primary hyperparathyroidism and in hyperparathyroidism secondary to chronic renal failure

In patients with uremia, intact parathyroid hormone (PTH) measurement appears to overestimate the biologically active hormone in circulation. The recent description of the accumulation in these patients of a non-intact PTH form measured by the standard immunometric assays, re-opened the question. In this study we submitted serum samples from 7 patients with primary hyperparathyroidism (PHP) and from 10 patients with hyperparathyroidism secondary to chronic renal failure (SHP) to preparative HPLC in order to discriminate the molecular forms measured by our currently used immunofluorometric assay for intact PTH. The elution profile obtained with the HPLC system showed two clearly defined peaks, the first one corresponding to a lower molecular weight form, and the second to the intact PTH (1-84) form. In patients with SHP the area under the curve for the first peak (mean 29.5%, range 20.6 to 40.4%) was significantly greater than that observed for patients with PHP (mean 15.6%, range 5.6 to 21.9%). This confirms previous studies showing accumulation of molecular forms of slightly lower molecular weight, presumably PTH (7-84), in patients with SHP and, to a lesser extent, in patients with PHP. The real necessity of assays that discriminate between these two molecular forms is debatable.

Angiotensin and baroreflex control of the circulation

There is a close association between the location of angiotensin (Ang) receptors and many important brain nuclei involved in the regulation of the cardiovascular system. The present review encompasses the physiological role of Ang II in the brainstem, particularly in relation to its influence on baroreflex control of the heart and kidney. Activation of AT1 receptors in the brainstem by fourth ventricle (4V) administration to conscious rabbits or local administration of Ang II into the rostral ventrolateral medulla (RVLM) of anesthetized rabbits acutely increases renal sympathetic nerve activity (RSNA) and RSNA baroreflex responses. Administration of the Ang antagonist Sarile into the RVLM of anesthetized rabbits blocked the effects of Ang II on the RSNA baroreflex, indicating that the RVLM is the major site of sympathoexcitatory action of Ang II given into the cerebrospinal fluid surrounding the brainstem. However, in conscious animals, blockade of endogenous Ang receptors in the brainstem by the 4V AT1 receptor antagonist losartan resulted in sympathoexcitation, suggesting an overall greater activity of endogenous Ang II within the sympathoinhibitory pathways. However, the RSNA response to airjet stress in conscious rabbits was markedly attenuated. While we found no effect of acute central Ang on heart rate baroreflexes, chronic 4V infusion inhibited the baroreflex and chronic losartan increased baroreflex gain. Thus, brainstem Ang II acutely alters sympathetic responses to specific afferent inputs thus forming part of a potentially important mechanism for the integration of autonomic response patterns. The sympathoexcitatory AT1 receptors appear to be activated during stress, surgery and anesthesia.

Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson’s correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

Miringosclerose em pacientes com insuficiência renal crônica: análise comparativa com um grupo controle

A miringoesclerose é uma alteração cicatricial da lâmina própria da membrana timpânica caracterizada por proliferação de fibras colágenas, seguida de hialinização, deposição de cálcio e fósforo, seguindo uma seqüência semelhante ao que ocorre em outros tipos de calcificação patológica comuns em pacientes com doença renal crônica. OBJETIVO: Verificar a influencia da insuficiência renal crônica (IRC) na prevalência da miringoesclerose. MÉTODO: Foi realizada otoscopia em 341 pacientes com IRC em hemodiálise e em 356 indivíduos de um grupo controle. Foi comparada a freqüência de otoscopia positiva entre os dois grupos, procurando-se relacionar com variáveis pessoais e relacionadas a IRC. RESULTADOS: O grupo de pacientes apresentou 11,7% de otoscopia positiva contra 5,1% do grupo controle. Não houve influência do sexo ou cor na freqüência da miringoesclerose. Porém, os grupos foram heterogêneos em relação à faixa etária. Também não houve diferença importante no tempo de diálise nem nos níveis séricos de minerais e do PTH entre os pacientes do grupo de estudo que apresentavam otoscopia positiva ou negativa. CONCLUSÃO: Os achados, embora apontem para uma maior ocorrência da miringoesclerose nos pacientes renais crônicos, não nos permitem concluir com certeza que exista alguma relação entre a IRC e as alterações timpânicas.

Costos de intervenciones para pacientes con insuficiencia renal crónica

INTRODUCCIÓN: Se presentan resultados sobre un estudio que pretendió identificar los costos de intervenciones en salud en el manejo de pacientes con insuficiencia renal crónica. MATERIAL Y MÉTODO: El método de costeo se basó en técnicas de consenso y de instrumentación de manejo de caso a través de la identificación de insumos y funciones de producción para la demanda de cada servicio solicitado. Las intervenciones costeadas incluyeron: diálisis peritoneal, hemodiálisis y trasplante renal. RESULTADOS: El costo por evento en US dóllares fué de $3.71, $57.95 y $ 8,778.32 respectivamente. En cuanto al costo de manejo anual de caso los resultados fueron: diálisis peritoneal $5,643.07, hemodiálisis $9,631.60 y trasplante $3,021.67. CONCLUSIONES: La información generada a partir de los costos de eventos difiere considerablemente de la información generada a partir del costo de manejo anual de caso. Estas diferencias resultan significativas para el diseño y evaluación de patrones de asignación de recursos

Costo-efectividad de intervenciones para insuficiencia renal crónica terminal

OBJETIVO: Analisó el costo-efectividad en intervenciones para pacientes con insuficiencia renal crónica terminal (IRCT) en términos de los costos económicos de cada intervención, los años de vida ganados y la calidad de vida que generan tres alternativas comparables y mutuamente excluyentes: diálisis peritoneal contínua ambulatoria (DPCA), la hemodiálisis (HD) y el trasplante renal (TR). MÉTODO: El diseño del estudio fue de tipo longitudinal. Los costos de cada intervención se determinaron mediante la técnica de manejo de caso promedio. Las medidas para evaluar los criterios de efectividad elegidos fueron la probabilidad de sobrevida y el Año de Vida Ajustado por Calidad (QALY, Quality Adjusted Life Year) medido por el Indice de Rosser. RSULTADOS: Los costos de manejo anual de caso fueron: diálisis peritoneal $5,643.07, hemodiálisis $9,631.60 y trasplante $3,021.63. En cuanto a la efectividad, la sobrevida del injerto de trasplante renal resultó de 89,9% y 79,6% a uno y tres años respectivamente, mientras que los pacientes sometidos a DPCA tienen una sobrevida de 86,2% y 66,9% a un año y a tres años respectivamente. En cuanto a los QALY's, los resultados para cada intervención fueron: DPCA 0,879; HD 0,864; y para el TR 0,978. CONCLUSIÓN: La intervención más costo-efectiva resultó el trasplante renal con un coeficiente de 3,088.69, seguido de la DPCA y la hemodiálisis, cuyos coeficientes fueron de 6,416.95 y 11,147.68 respectivamente. Por lo tanto se recomienda promover y utilizar el trasplante renal como la intervención más costo-efectiva para pacientes con IRCT.

Serological analysis reveals circulation of influenza C viruses, Brazil

The circulation of influenza C viruses in Rio de Janeiro, Brazil, was studied when significant levels of antibodies were detected (56.7%) with hemagglutination inhibition test, used as a standard methodology for influenza virus studies.

Perfil epidemiológico dos pacientes em terapia renal substitutiva no Brasil, 2000-2004

OBJETIVO: Descrever o perfil epidemiológico e clínico de pacientes em terapia renal substitutiva, identificando fatores associados ao risco de morte. MÉTODOS: Estudo observacional, prospectivo não concorrente, a partir de dados de 90.356 pacientes da Base Nacional em Terapias Renais Substitutivas, no Brasil. Foi realizado relacionamento determinístico-probabilístico do Sistema de Autorização de Procedimentos de Alta Complexidade/Custo e do Sistema de Informação de Mortalidade. Foram incluídos todos os pacientes incidentes que iniciaram diálise entre 1/1/2000 e 31/12/2004, acompanhados até a morte ou final de 2004. Idade, sexo, região de residência, doença renal primária, causa do óbito foram analisados. Ajustou-se um modelo de riscos proporcionais para identificar fatores associados ao risco de morte. RESULTADOS: Ocorreu um aumento médio de 5,5% na prevalência de pacientes em terapia enquanto a incidência manteve-se estável no período. Hemodiálise foi a modalidade inicial predominante (89%). A maioria dos pacientes era do sexo masculino, com idade média de 53 anos, residente na região Sudeste, e apresentava causa indeterminada como principal causa básica da doença renal crônica, seguida da hipertensão, diabetes e glomerulonefrites. Desses pacientes, 7% realizou transplante renal e 42% evoluiu para o óbito. Os pacientes em diálise peritoneal eram mais idosos e apresentavam maior prevalência de diabetes. Entre os não transplantados, 45% foi a óbito e, entre os transplantados, 7%. No modelo final de riscos proporcionais de Cox, o risco de mortalidade foi associado com o aumento da idade, sexo feminino, ter diabetes, residir nas regiões Norte e Nordeste, diálise peritoneal como modalidade de entrada e não ter realizado transplante renal. CONCLUSÕES: Houve aumento da prevalência de pacientes em terapia renal no Brasil. Pacientes com idade avançada, diabetes, do sexo feminino, residentes nas regiões Norte e Nordeste e sem transplante renal apresentam maior risco de morte.

Permanent vascular access in patients with end-stage renal disease, Brazil

OBJECTIVE: To assess factors associated with the establishment of permanent vascular access for patients with end-stage renal disease. METHODS: Cross-sectional study conducted in a nationally representative sample of Brazilian end-stage renal disease patients in dialysis and transplant centers during 2007. The sample comprised only patients who received hemodialysis as a primary therapy modality and reported the type of vascular access for their primary hemodialysis treatment (N=2,276). Data were from the TRS Project - "Economic and Epidemiologic Evaluation of Modalities of Renal Replacement Therapy in Brazil". Multiple logistic regression analysis was used to assess factors associated with the establishment of permanent vascular access in these patients. RESULTS: About 30% of the patients studied had an arteriovenous vascular access. The following factors were associated with a lower likelihood of having an arteriovenous vascular access as a primary type of access: time of hemodialysis start since the diagnosis of chronic renal failure < 1 year; shorter dialysis therapy; having no private health insurance; living in the central-western, northeastern and southeastern regions of Brazil; and living in the northern region plus having no private health insurance. In the final model there was found a positive association between the outcome and pre-dialysis care and no were association with socioeconomic and comorbidity variables. CONCLUSIONS: The study results showed that the focus should on pre-dialysis care to increase the establishment of an arteriovenous vascular access before starting hemodialysis in Brazil.

Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil

OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation.METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results.RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44.CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. However, regimens containing cyclosporine were more cost-effective.

Histoplasmose disseminada em transplantado renal

Os Autores registram caso de histoplasmose generalizada em paciente transplantado com rim de doador não aparentado. Além da infecção fúngica diagnosticada sorologicamente e pela histopatologia, a autópsia revelou cirrose hepática macro e micronodular, de provável etiologia viral (vírus B), hepatocarcinoma, depleção linfóide do baço e glomerulopatia de transplante. Revendo a literatura sobre o assunto, chegam à conclusão de que, provavelmente, com a imunodepressão medicamentosa, as lesões pulmonares por reinfecção endógena foram as primeiras a aparecer sob a forma de uma histoplasmose pulmonar crônica.