Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g). Chronic acidosis (pH 7.16 ± 0.13) caused a sustained increase in renal fractional Na+ excretion (267.9 ± 36.4%), accompanied by an increase in fractional proximal (113.3 ± 3.6%) and post-proximal (179.7 ± 20.2%) Na+ and urinary K+ (163.4 ± 5.6%) excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g) and pair-fed (225 ± 3.6 g) rats compared to the controls (258 ± 3.7 g). In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g) compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g). We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats

The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 176.6 ± 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 163.8 ± 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 ± 67 µL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 ± 26 µL min-1 100 g body weight-1) and captopril-treated (903 ± 72 µL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 ± 0.019% compared to 0.126 ± 0.041 and 0.66 ± 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 ± 0.05%) was significantly lower (P = 0.0063) than in control (0.91 ± 0.15%) and captopril-treated rats (1.24 ± 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

New strategies are being devised to limit the impact of renal sclerosis on graft function. Individualization of immunosuppression, specifically the interruption of calcineurin-inhibitors has been tried in order to promote better graft survival once chronic graft dysfunction has been established. However, the long-term impact of these approaches is still not totally clear. Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF) development should be carefully monitored for tubular function as well as glomerular performance. Since tubular-interstitial impairment is an early event in TA/IF pathogenesis and associated with graft function, it seems reasonable that strategies directed at assessing tubular structural integrity and function would yield important functional and prognostic data. The measurement of small proteins in urine such as α-1-microglobulin, N-acetyl-beta-D-glucosaminidase, alpha/pi S-glutathione transferases, β-2 microglobulin, and retinol binding protein is associated with proximal tubular cell dysfunction. Therefore, its straightforward assessment could provide a powerful tool in patient monitoring and ongoing clinical assessment of graft function, ultimately helping to facilitate longer patient and graft survival associated with good graft function.

Consequences of cerebroventricular insulin injection on renal sodium handling in rats: effect of inhibition of central nitric oxide synthase

In the present study, we investigated the effects of acute intracerebroventricular (icv) insulin administration on central mechanisms regulating urinary sodium excretion in simultaneously centrally NG-nitro-L-arginine methylester (L-NAME)-injected unanesthetized rats. Male Wistar-Hannover rats were randomly assigned to one of five groups: a) icv 0.15 M NaCl-injected rats (control, N = 10), b) icv dose-response (1.26, 12.6 and 126 ng/3 µL) insulin-injected rats (N = 10), c) rats icv injected with 60 µg L-NAME in combination with NaCl (N = 10) or d) with insulin (N = 10), and e) subcutaneously insulin-injected rats (N = 5). Centrally administered insulin produced an increase in urinary output of sodium (NaCl: 855.6 ± 85.1 Δ%/min; 126 ng insulin: 2055 ± 310.6 Δ%/min; P = 0.005) and potassium (NaCl: 460.4 ± 100 Δ%/min; 126 ng insulin: 669.2 ± 60.8 Δ%/min; P = 0.025). The urinary sodium excretion response to icv 126 ng insulin microinjection was significantly attenuated by combined administration of L-NAME (126 ng insulin: 1935 ± 258.3 Δ%/min; L-NAME + 126 ng insulin: 582.3 ± 69.6 Δ%/min; P = 0.01). Insulin-induced natriuresis occurred by increasing post-proximal sodium excretion, despite an unchanged glomerular filtration rate. Although the rationale for decreased urinary sodium excretion induced by combined icv L-NAME and insulin administration is unknown, it is tempting to suggest that perhaps one of the efferent signals triggered by insulin in the CNS may be nitrergic in nature.

Pesquisa de doença aterosclerótica multiarterial em pacientes hipertensos com estenose de artéria renal

INTRODUÇÃO: A detecção de estenose de artéria renal em pacientes hipertensos pode ser um sinal de aterosclerose arterial sistêmica. OBJETIVOS: Identificar e caracterizar do ponto de vista clínico e epidemiológico os pacientes hipertensos com estenose de artéria renal, avaliando fatores de risco cardiovascular e presença de doença aterosclerótica multiarterial sintomática. MÉTODO: Foram selecionados os pacientes hipertensos atendidos no ambulatório de Nefrologia da Universidade Federal do Triângulo Mineiro (UFTM) entre 2000-2010, com diagnóstico de estenose de artéria renal de etiologia aterosclerótica. Avaliaram-se dados epidemiológicos (gênero, idade, etnia), fatores de risco cardiovascular (Diabetes Mellitus, hipercolesterolemia, hipertrigliceridemia, tabagismo, síndrome metabólica), informações relativas à hipertensão (tempo de diagnóstico, histórico familiar, número de medicamentos utilizados), eventos cardiovasculares prévios (infarto agudo do miocárdio, acidente vascular encefálico isquêmico, doença arterial periférica). Estratificaram-se os níveis pressóricos, risco cardiovascular global e escore Framingham. RESULTADOS: Casuística de 30 pacientes, maioria feminina (73,3%), média de idade de 66 anos, 86,67% brancos. Tempo médio de HAS de 19,94 anos, 89,28% sem histórico familiar, 13,8% com diabetes, 65,51% tabagistas, 17,25% com hipertrigliceridemia, 62,06% com hipercolesterolemia e 66,7% com síndrome metabólica. Número médio de medicamentos em uso: 3,26. Estenose de artéria renal predominante à direita quando isoladamente (46,7%) e em terço proximal (56,7%). Creatinina elevada em 40% dos pacientes. Quanto ao estágio de hipertensão, maioria estágio 2 (47%) e 73,3% com risco cardiovascular global alto. Escore Framingham Médio de 13%. 66,7% apresentavam doença aterosclerótica em outro sítio, sendo coronariano o principal (53,3%). CONCLUSÃO: A correlação mais comum foi com o infarto agudo do miocárdio, o que implica na busca do comprometimento coronário quando do diagnóstico de estenose de artéria renal em pacientes hipertensos, para tentar evitar danos futuros ao paciente.

Calcium citrate improves the epithelial-to-mesenchymal transition induced by acidosis in proximal tubular cells

INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF) β1 role and citrate effect on it. METHODS: HK2 cells (ATCC 2290) were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours): A) Control: pH 7.4, B) Acidosis: pH 7.0 and C) Calcium citrate (0.2 mmol/L) + pH 7.0. Change (Δ) of intracellular calcium concentration, basal and after Angiotensin II (10-6M) exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA) and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant. RESULTS: At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT). Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production. CONCLUSIONS: Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.

Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients

The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2), became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties (“second-generation”) were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors. Conclusion: Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients.

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.

Aplicação de medidas de ajuste de risco para a mortalidade após fratura proximal de fêmur

OBJETIVO: Analisar os fatores associados à mortalidade em pacientes para tratamento da fratura proximal do fêmur e as diferentes formas de ajuste de risco. MÉTODOS: Estudo de coorte não-concorrente com 390 pacientes com 50 anos ou mais. Os pacientes foram identificados no Sistema de Informações Hospitalares do Sistema Único de Saúde, internados para correção cirúrgica da fratura proximal do fêmur em um hospital universitário do município do Rio de Janeiro, entre 1995 e 2000. Foram levantados dados complementares nos prontuários desses pacientes e elaborados modelos de regressão logística para a chance de óbito em 90 dias após a data da admissão, segundo perfil dos pacientes e do tratamento. Foram calculados índices de classificação da gravidade do paciente. RESULTADOS: A taxa de mortalidade foi de 7,4% e os fatores que tiveram efeito sobre o óbito foram: idade (OR=1,06; IC 95%: 1,02;1,11), quantidade de comorbidades (OR=1,44; IC 95%: 1,12;1,69), índice de comorbidade de Charlson acima de 2 (OR=6,67; IC 95%: 2,98;22,16) e intervalo de tempo para a realização da cirurgia (OR=1,04; IC 95%:1,02;1,07). CONCLUSÕES: A quantidade de comorbidades e o índice de comorbidade de Charlson auxiliaram na predição da mortalidade.

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.