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Resumo Fundamento Os bloqueadores dos receptores da angiotensina (BRA) e os inibidores da enzima conversora da angiotensina (IECA) aumentam a expressão de ACE2, que é um receptor para entrada de SARS-CoV-2 nas células. Embora as evidências sugiram que os IECA/BRA são seguros entre a população geral com COVID-19, sua segurança em pacientes com hipertensão relacionada ao sobrepeso/obesidade merece uma avaliação mais aprofundada. Objetivo Avaliamos a associação entre o uso de IECA/BRA e a gravidade da COVID-19 em pacientes com hipertensão relacionada ao sobrepeso/obesidade. Métodos O presente estudo incluiu 439 pacientes adultos com sobrepeso/obesidade (índice de massa corporal ≥ 25 kg/m2) e hipertensão, diagnosticados com COVID-19 e internados no University of Iowa Hospitals and Clinic entre 1º de março e 7 de dezembro de 2020. Foram avaliadas a mortalidade e a gravidade da COVID-19 com base no tempo de internação hospitalar, internação em unidade de terapia intensiva, uso de oxigênio suplementar, ventilação mecânica e uso de vasopressores. A regressão logística multivariável foi usada para examinar as associações do uso de IECA/BRA com a mortalidade e outros marcadores de gravidade de COVID-19, com um alfa bilateral definido em 0,05. Resultados A exposição aos BRA (n = 91) e IECA (n = 149) antes da hospitalização foi significativamente associada a menor mortalidade ( odds ratio [OR] = 0,362, intervalo de confiança [IC] de 95% 0,149 a 0,880, p = 0,025) e menor tempo de internação hospitalar (IC 95% −0,217 a −0,025, p = 0,015). Adicionalmente, os pacientes em uso de IECA/BRA apresentaram uma tendência não significativa de menor internação em unidade de terapia intensiva (OR = 0,727, IC 95% 0,485 a 1,090, p = 0,123), uso de oxigênio suplementar (OR = 0,929, IC 95% 0,608 a 1,421,p = 0,734), ventilação mecânica (OR = 0,728, IC 95% 0,457 a 1,161, p = 0,182) e vasopressores (OR = 0,677, IC 95% 0,430 a 1,067, p = 0,093). Conclusão Os resultados sugerem que pacientes internados com COVID-19 e hipertensão relacionada ao sobrepeso/obesidade que receberam IECA/BRA antes da internação apresentam menor mortalidade e COVID-19 menos grave do que aqueles que não estavam tomando IECA/BRA. Os resultados também sugerem que a exposição aos IECA/BRA pode proteger pacientes com hipertensão relacionada ao sobrepeso/obesidade de COVID-19 grave e morte. Abstract Background Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) increase the expression of ACE2, which is a receptor for entry of SARS-CoV-2 into cells. Though evidence suggests that ARB/ACEI are safe among the general population with COVID-19, their safety in patients with overweight/obesity-related hypertension deserves further evaluation. Objective We assessed the association between ARB/ACEI use and COVID-19 severity in patients with overweight/obesity-related hypertension. Methods This study included 439 adult patients with overweight/obesity (body mass index ≥ 25 kg/m2) and hypertension, diagnosed with COVID-19 and admitted to University of Iowa Hospitals and Clinic from March 1 to December 7, 2020. Mortality and severity of COVID-19 were evaluated based on length of stay in hospital, intensive care unit admission, use of supplemental oxygen, mechanical ventilation, and vasopressors. Multivariable logistic regression was used to examine the associations of ARB/ACEI use with mortality and other markers of COVID-19 severity, with a two-sided alpha set at 0.05. Results Exposure to ARB (n = 91) and ACEI (n = 149) before hospitalization was significantly associated with lower mortality (odds ratio [OR] = 0.362, 95% confidence interval [CI] 0.149 to 0.880, p = 0.025) and a shorter length of stay (95% CI −0.217 to −0.025, p = 0.015). Additionally, patients using ARB/ACEI showed a non-significant trend toward lower intensive care unit admission (OR = 0.727, 95% CI 0.485 to 1.090, p = 0.123), use of supplemental oxygen (OR = 0.929, 95% CI 0.608 to 1.421, p = 0.734), mechanical ventilation (OR = 0.728, 95% CI 0.457 to 1.161, p = 0.182), and vasopressors (OR = 0.677, 95% CI 0.430 to 1.067, p = 0.093). Conclusion Results suggest that hospitalized patients with COVID-19 and overweight/obesity-related hypertension who were prescribed ARB/ACEI before admission to the hospital exhibit lower mortality and less severe COVID-19 than those who were not taking ARB/ACEI. The results also suggest that exposure to ARB/ACEI may protect patients with overweight/obesity-related hypertension from severe COVID-19 and death.

RESUMEN Introducción: Actualmente existe un gran interés en establecer la relación entre la severidad de la infección por SARS-COV-2 en pacientes hipertensos usuarios de antagonistas de la angiotensina II (ARAII). Objetivo: Estudiar la relación entre el uso previo de antagonistas de la ARA II en pacientes hipertensos y la mortalidad por COVID-19. Materiales y métodos: Se realizó un estudio observacional retrospectivo en un hospital de referencia en Lima, Perú, en pacientes hipertensos hospitalizados en marzo del 2021 por COVID-19 severo. Resultados: Ingresaron al estudio 101 pacientes, con una media de edad de 70.1 + 12.0 y sexo masculino 48%. Los usuarios de ARAII fueron 45 (45.6%) y no los tomaban 56 (54.4%). El Índice de comorbilidad de Charlson fue mayor en el grupo ARAII (3.6 + 1.56 vs 3.04 + 1.24) (p

Dystrophin-deficient cardiomyopathy (DDC) is currently the leading cause of death in patients with dystrophinopathies. Targeting myocardial fibrosis (MF) has become a major therapeutic goal in order to prevent the occurrence of DDC. We aimed to review and summarize the current evidence about the role of the renin-angiotensin-aldosterone system (RAAS) in the development and perpetuation of MF in DCC. We conducted a comprehensive search of peer-reviewed English literature on PubMed about this subject. We found increasing preclinical evidence from studies in animal models during the last 20 years pointing out a central role of RAAS in the development of MF in DDC. Local tissue RAAS acts directly mainly through its main fibrotic component angiotensin II (ANG2) and its transducer receptor (AT1R) and downstream TGF-b pathway. Additionally, it modulates the actions of most of the remaining pro-fibrotic factors involved in DDC. Despite limited clinical evidence, RAAS blockade constitutes the most studied, available and promising therapeutic strategy against MF and DDC. Conclusion: Based on the evidence reviewed, it would be recommendable to start RAAS blockade therapy through angiotensin converter enzyme inhibitors (ACEI) or AT1R blockers (ARBs) alone or in combination with mineralocorticoid receptor antagonists (MRa) at the youngest age after the diagnosis of dystrophinopathies, in order to delay the occurrence or slow the progression of MF, even before the detection of any cardiovascular alteration. Yes

It is unclear to which extent the higher mortality associated with hypertension in the coronavirus disease (COVID-19) is due to its increased prevalence among older patients or to specific mechanisms. Cross-sectional, observational, retrospective multicenter study, analyzing 12226 patients who required hospital admission in 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics of survivors versus non-survivors. The mean age of the study population was 67.5 &plusmn, 16.1 years, 42.6% were women. Overall, 2630 (21.5%) subjects died. The most common comorbidity was hypertension (50.9%) followed by diabetes (19.1%), and atrial fibrillation (11.2%). Multivariate analysis showed that after adjusting for gender (males, OR: 1.5, p = 0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p = 0.0001), and Charlson Comorbidity Index scores (second and third tertiles, OR: 4.7 and 8.1, p = 0.0001), hypertension was significantly predictive of all-cause mortality when this comorbidity was treated with angiotensin-converting enzyme inhibitors (ACEIs) (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (ARBs) (OR: 1.2, p = 0.035). The preexisting condition of hypertension had an independent prognostic value for all-cause mortality in patients with COVID-19 who required hospitalization. ARBs showed a lower risk of lethality in hypertensive patients than other antihypertensive drugs.

Objetivo: Comparar el efecto nefroprotector a largo plazo con los grupos de medicamentos ARA II e IECA. Material y métodos: Observacional, transversal, retrospectivo, analítico. En la recolección de datos buscamos expedientes de la UMF 30 de pacientes con diabetes mellitus que estén bajo tratamiento con ARA II o IECA exclusivamente, se excluyen si están bajo otro antihipertensivo, posterior a esto dividimos los expedientes en dos grupos. Resultados: Se realizo un estudio con 70 pacientes divididos en dos grupos ARAII e IECAS en el grupo de los ARA II fueron 13 masculinos es decir 37.1% y 22 femeninas 62.9% en el segundo grupo que son los IECA fueron 9 masculinos 25.7% y 26 femeninas es decir 74.3%. Conclusiones: Se pudo demostrar que el efecto nefroprotector a largo plazo ya sea de ARA II o IECA es similar en nuestra población de estudio.

Portugal presents the highest incidence of stage 5 chronic kidney disease in Europe. It is speculated that a high consumption of non-steroidal anti-inflammatory drugs (NSAIDS) may contribute to this high incidence. Our aim was to characterize the prescription of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus in Portugal.We analyzed the national prescription database in triennium 2015 - 2017. In patients with diabetes mellitus, we evaluated the prescription of non-steroidal anti-inflammatory drugs according to age, gender and region of the patient and specialty of the prescribing physician. We evaluated the prescription of non-steroidal anti-inflammatory drugs in all patients with diabetes mellitus, in patients with presumed renal impairment, and in those with concomitant prescription of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists.We analyzed 23 320 620 prescriptions, corresponding to 610 157 adults, including 104 306 patients with diabetes mellitus. The most prescribed non-steroidal anti-inflammatory drugs were ibuprofen (20.1%), metamizole (14.7%), and diclofenac (11.4%). The prescription of non-steroidal anti-inflammatory drugs was higher in females, in patients aged 51 - 70 years and in the Alentejo region. Non-steroidal anti-inflammatory drugs were prescribed to 70.6% of patients with diabetes mellitus, from which 10.6% were prescribed ≥ 10 packages during the three years. Among patients with diabetes mellitus on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and with presumed reduction in kidney function, 69.3% were prescribed non-steroidal anti-inflammatory drugs and 11.5% were prescribed ≥ 10 packages during the three years.The level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus is high. The concern of reducing non-steroidal anti-inflammatory drugs prescription to patients already on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and/or decreased renal function does not seem to exist.In Portugal, the level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus should be reduced, particularly in the subgroups identified with higher prescription and with higher risk of progression to stage 5 chronic kidney disease.Introdução: Portugal apresenta a incidência mais elevada de doença renal crónica estádio 5 na Europa. Especula-se que o elevado consumo de anti-inflamatórios não esteroides possa contribuir para esta incidência. O objetivo do presente estudo foi caracterizar a prescrição de anti-inflamatórios não esteroides a doentes com diabetes mellitus em Portugal. Material e Métodos: Na Base de Dados Nacional de Prescrições do Ministério da Saúde, triénio 2015 - 2017, analisámos a prescrição de anti-inflamatórios não esteroides em doentes com diabetes mellitus, de acordo com a idade, género e região do doente e a especialidade do médico prescritor. Avaliámos a prescrição de anti-inflamatórios não esteroides no total de doentes com diabetes mellitus, em doentes com diminuição presumida da função renal e naqueles com prescrição concomitante de inibidores da enzima de conversão da angiotensina ou antagonistas dos recetores da angiotensina. Resultados: Analisámos 23 320 620 prescrições, correspondendo a 610 157 adultos, dos quais 104 306 doentes com diabetes mellitus. Os anti-inflamatórios não esteroides mais prescritos foram ibuprofeno (20,1%), metamizol (14,7%) e diclofenac (11,4%). A prescrição foi mais frequente nas mulheres, nos doentes com 51 - 70 anos e no Alentejo. Foram prescritos anti-inflamatórios não esteroides a 70,6% dos doentes com diabetes mellitus, dos quais 10,6% receberam prescrições de ≥ 10 embalagens durante os três anos. Dos doentes com diabetes mellitus medicados com inibidores da enzima de conversão da angiotensina ou antagonistas dos receptores da angiotensina e com diminuição presumida da taxa de filtração glomerular, 69,3% receberam prescrição de anti-inflamatórios não esteroides e 11,5% receberam ≥ 10 embalagens durante os três anos. Discussão: A prescrição de anti-inflamatórios não esteroides na diabetes mellitus é elevada. Não parece existir uma preocupação na menor utilização de anti-inflamatórios não esteroides em doentes simultaneamente medicados com inibidores da enzima de conversão da angiotensina ou antagonistas dos recetores da angiotensina e/ou com diminuição da função renal. Conclusão: A prescrição de anti-inflamatórios não esteroides em Portugal a doentes com diabetes mellitus deverá ser reduzida, particularmente nos subgrupos identificados com prescrição mais elevada e com maior risco de progressão para doença renal crónica estádio 5.

INTRODUCTION: Portugal presents the highest incidence of stage 5 chronic kidney disease in Europe. It is speculated that a high consumption of non-steroidal anti-inflammatory drugs (NSAIDS) may contribute to this high incidence. Our aim was to characterize the prescription of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus in Portugal. MATERIAL AND METHODS: We analyzed the national prescription database in triennium 2015 - 2017. In patients with diabetes mellitus, we evaluated the prescription of non-steroidal anti-inflammatory drugs according to age, gender and region of the patient and specialty of the prescribing physician. We evaluated the prescription of non-steroidal anti-inflammatory drugs in all patients with diabetes mellitus, in patients with presumed renal impairment, and in those with concomitant prescription of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists. RESULTS: We analyzed 23 320 620 prescriptions, corresponding to 610 157 adults, including 104 306 patients with diabetes mellitus. The most prescribed non-steroidal anti-inflammatory drugs were ibuprofen (20.1%), metamizole (14.7%), and diclofenac (11.4%). The prescription of non-steroidal anti-inflammatory drugs was higher in females, in patients aged 51 - 70 years and in the Alentejo region. Non-steroidal anti-inflammatory drugs were prescribed to 70.6% of patients with diabetes mellitus, from which 10.6% were prescribed ≥ 10 packages during the three years. Among patients with diabetes mellitus on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and with presumed reduction in kidney function, 69.3% were prescribed non-steroidal anti-inflammatory drugs and 11.5% were prescribed ≥ 10 packages during the three years. DISCUSSION: The level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus is high. The concern of reducing non-steroidal anti-inflammatory drugs prescription to patients already on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and/or decreased renal function does not seem to exist. CONCLUSION: In Portugal, the level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus should be reduced, particularly in the subgroups identified with higher prescription and with higher risk of progression to stage 5 chronic kidney disease. info:eu-repo/semantics/publishedVersion

Introduction: Renal involvement is a severe form of schistosomiasis and occurs in 10% to 15% of patients with the hepatosplenic form of the disease. Nephrotic syndrome is the most common clinical presentation. It is a complication caused by immune complexes (IC), it is rare to appear in the Brazilian context with a immunoglobulin A (IgA) deposits. When installed the renal injury by Schistosoma mansoni, classically presents as membranoproliferative glomerulonephritis (mesangiocapillary) with lobular accentuation. Objective: To report a case of schistosomiasis nephropathy that appeared 7 years after treatment of hepatosplenic schistosomiasis with histologic pattern of mesangial proliferative glomerulonephritis with IgA deposits in mesangium. Clinically developed with progressive decrease of proteinuria with angiotensin receptor blocker (ARB). Method: It was reported a case of a 36 years old patient, brown, with classical sintoms of nephrotic syndrome (proteinuria > 3.5 g/24h, hypoalbuminemia and hypercholesterolemia), however with hepatosplenic schistosomiasis history 7 years ago and portal hypertension. Patient underwent renal biopsy which showed IgA deposits in mesangial, being more intense than immunoglobulin G (IgG), accompanied by C1q and C3, with 4/13 glomeruli sclerotic, standard light mesangial glomerulonephritis renal injury with IgA deposits. Patient began taking ARB with progressive improvement in proteinuria. Conclusion: Patients with glomerulonephritis by schistosoma don't show improvement of disease progression with antiparasitic treatment. However the anti-proteinuric treatment can slow the progression of end stage kidney disease. Resumo Introdução: O acometimento renal é uma forma grave da esquistossomose e ocorre em 10% a 15% dos pacientes com a forma hepatoesplênica da doença. A síndrome nefrótica é a apresentação clínica mais comum. Trata-se de uma complicação causada por imunocomplexos (IC), sendo rara no contexto brasileiro apresentar-se com depósitos de imunoglobulina A (IgA). Quando instalada a lesão renal pelo Schistosoma mansoni, apresenta-se classicamente como glomerulonefrite membranoproliferativa (mesangiocapilar), com acentuação lobular. Objetivo: Relatar caso de glomerulopatia esquistossomótica que se apresentou 7 anos após tratamento de esquistossomose hepatoesplênica com padrão histológico de glomerulonefrite proliferativa mesangial com depósitos de IgA em mesângio. Clinicamente, evoluiu com diminuição progressiva de proteinúria com bloqueador do receptor de angiotensina (BRA). Método: Foi relatado caso de paciente com 36 anos, parda, com quadro clássico de síndrome nefrótica (proteinúria > 3,5 g/24h, hipoalbuminemia e hipercolesterolemia), no entanto, com histórico de esquistossomose hepatoesplênica há 7 anos e com hipertensão portal. Paciente foi submetida à biópsia renal, que apresentou depósitos de IgA em mesângio, sendo mais intensos que imunoglobulina G (IgG), acompanhados de C1q e C3, com 4/13 glomérulos esclerosados, padrão de lesão renal de glomerulopatia mesangial leve com depósitos de IgA. Paciente iniciou uso de BRA, com melhora progressiva da proteinúria. Conclusão: Pacientes com glomerulopatia por schistosoma não apresentam melhora da progressão da doença com tratamento antiparasitário. Entretanto, o tratamento antiproteinúrico pode retardar a progressão da doença renal crônica terminal.

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant.

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant. Introdução: Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos. Relato do caso: Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado. Discussão: Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado. Conclusão: A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão em idade reprodutiva e que podem se tornar gestantes em uso rotineiro destas medicações.

Drug selection methods with scores have been developed and used worldwide for formulary purposes. These tools focus on the way in which the products are differentiated from each other within the same therapeutic class. Scoring Analytical Tool (SAT) is designed based on the same principle with score and is able to assist formulary committee members in evaluating drugs either to add or delete in a more structured, consistent and reproducible manner. Objective: To develop an objective SAT to facilitate evaluation of drug selection for formulary listing purposes. Methods: A cross-sectional survey was carried out. The proposed SAT was developed to evaluate the drugs according to pre-set criteria and sub-criteria that were matched to the diseases concerned and scores were then assigned based on their relative importance. The main criteria under consideration were safety, quality, cost and efficacy. All these were converted to questionnaires format. Data and information were collected through self-administered questionnaires that were distributed to medical doctors and specialists from the established public hospitals. A convenient sample of 167 doctors (specialists and non-specialists) were taken from various disciplines in the outpatient clinics such as Medical, Nephrology and Cardiology units who prescribed ARBs hypertensive drugs to patients. They were given a duration of 4 weeks to answer the questionnaires at their convenience. One way ANOVA, Kruskal Wallis and post hoc comparison tests were carried out at alpha level 0.05. Results: Statistical analysis showed that the descending order of ARBs preference was Telmisartan or Irbesartan or Losartan, Valsartan or Candesartan, Olmesartan and lastly Eprosartan. The most cost saving ARBs for hypertension in public hospitals was Irbesartan. Conclusion: SAT is a tool which can be used to reduce the number of drugs and retained the most therapeutically appropriate drugs in the formulary, to determine most cost saving drugs and has the potential to complement the conventional method of drug selection as it is effective in aiding decision making process through the pre-established criteria and increasing scientific ground of decisions and transparency. Se han desarrollado y utilizado alrededor del mundo métodos de selección de medicamentos para inclusión en formularios. Estos instrumentos se basan en el modo en que los productos se diferencian entre si dentro del mismo grupo terapéutico. El Scoring Analytical Tool (SAT) se diseñó basado en el mismo principio mediante puntos y puede ayudar a los miembros del comité de formulario a evaluar medicamentos o a añadir o eliminar de un modo más estructurado e reproducible. Objetivo: Desarrollar un SAT objetivo para facilitar la evaluación de la selección de medicamentos para creación de listas de formulario. Métodos: Se realizó un estudio transversal. Se desarrolló un STA propuesto para evaluar medicamentos de acuerdo a criterios y sub-criterios pre-establecidos que se emparejaron a las enfermedades en cuestión y a los que se dio una puntuación en base a su importancia. Los criterios principales considerados fueron seguridad, calidad, coste y eficacia. Todos estos fueron convertidos en formato cuestionario. La información fue recogida a través de cuestionarios auto-administrados que se distribuyeron a médicos y especialistas de hospitales públicos. Se creó una muestra de conveniencia de 167 médicos (especialistas y no especialistas) extraídos de varias disciplinas en clínicas ambulatorias tales como medicina, nefrología y cardiología, que prescribían antihipertensivos ARAII a pacientes. Se les dio un plazo de 4 semanas para responder la encuesta. Se realizaron testes ANOVA de una vuelta, Kruskal Wallis y comparaciones post hoc con un nivel alfa de 0.05. Resultados: Los análisis estadísticos demostraron que el orden descendente de preferencia de ARAII era Telmisartan o Irbesartan o Losartan, Valsartan o Candesartan, Olmesartan y finalmente Eprosartan. El ARAII más ahorrador para hipertensión en hospitales públicos era el Irbersartan. Conclusión: El SAT es un instrumento que pude usarse para reducir el número de medicamentos y mantener en el formulario los medicamentos terapéuticamente más apropiados, determinar los medicamentos más ahorradores, y tiene el potencial de complementar los métodos convencionales de selección de medicamentos, ya que añade al proceso de toma de decisiones unos criterios pre-establecidos y aumenta la base científica y la transparencia de las decisiones.

Introduction: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. Objective: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). Methods: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg); ¾ Nephrectomy receiving candesartan (10 mg/kg) and ¾ Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake, mean arterial pressure (MAP) and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL) -1β, IL-6, IL-10 and transforming growth factor beta (TGF-β) were measured. Results: Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1β, while only candesartan reduced TGF-β and only aliskiren increased IL-10. Conclusion: Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade. Resumo Introdução: Ainda não se sabe como a inibição farmacológica do Sistema Renina Angiotensina (SRA) afeta os níveis de biomarcadores de inflamação e fibrose. Objetivo: Este estudo pretendeu avaliar o efeito de enalapril, candesartan e alisquireno sobre os níveis urinários de citocinas em um modelo de doença renal crônica (DRC). Métodos: Ratos Wistar machos foram submetidos à remoção cirúrgica de ¾ do parênquima renal para induzir DRC (nefrectomia), ou submetidos à cirurgia fictícia (controle). Animais foram então randomizados em cinco grupos: Cirurgia fictícia recebendo veículo; Nefrectomia recebendo veículo; Nefrectomia recebendo enalapril (10 mg/kg); Nefrectomia recebendo candesartan (10 mg/kg) e Nefrectomia recebendo alisquireno (10 mg/kg). Débito urinário, ingesta hídrica, pressão arterial media (PAM) e concentrações urinárias de creatinina, ureia, albumina, Na+, K+, interleucina (IL) -1β, IL-6, IL-10 e fator de transformação e crescimento beta (TGF-β) foram medidas. Resultados: A nefrectomia comprometeu significativamente a função renal, aumentou a PAM e alterou os níveis de todas as citocinas avaliadas na urina. Enalapril, candesartan e alisquireno melhoraram a função renal e diminuíram a PAM e a IL-6 quando comparado aos grupo de animais nefrectomizados tratados com veículo. Candesartan e alisquireno reduziram IL-1β, enquanto somente candesartan diminuiu o TGF-β e somente alisquireno aumentou a IL-10. Conclusão: Enalapril, candesartan e alisquireno apresentaram efeitos similares em relação à melhora da função renal e redução da PAM e dos níveis urinários de IL-6 em ratos com DRC. Por outro lado, o perfil de citocinas diferiu de acordo com o tratamento, sugerindo que diferentes mecanismos sejam desencadeados em resposta ao local de bloqueio do SRA.

Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Left ventricular hypertrophy (LVH) is common in kidney transplant (KT) recipients. LVH is associated with a worse outcome, though m-TOR therapy may help to revert this complication. We therefore conducted a longitudinal study to assess morphological and functional echocardiographic changes after conversion from CNI to m-TOR inhibitor drugs in nondiabetic KT patients who had previously received RAS blockers during the follow-up. METHODS We undertook a 1-year nonrandomized controlled study in 30 non-diabetic KT patients who were converted from calcineurin inhibitor (CNI) to m-TOR therapy. A control group received immunosuppressive therapy based on CNIs. Two echocardiograms were done during the follow-up. RESULTS Nineteen patients were switched to SRL and 11 to EVL. The m-TOR group showed a significant reduction in LVMi after 1 year (from 62 ± 22 to 55 ± 20 g/m2.7; P=0.003, paired t-test). A higher proportion of patients showing LVMi reduction was observed in the m-TOR group (53.3 versus 29.3%, P=0.048) at the study end. In addition, only 56% of the m-TOR patients had LVH at the study end compared to 77% of the control group (P=0.047). A significant change from baseline in deceleration time in early diastole was observed in the m-TOR group compared with the control group (P=0.019). CONCLUSIONS Switching from CNI to m-TOR therapy in non-diabetic KT patients may regress LVH, independently of blood pressure changes and follow-up time. This suggests a direct non-hemodynamic effect of m-TOR drugs on cardiac mass. Yes