Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation

Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.

Isotonic sports drink promotes rehydration and decreases proteinuria following karate training / Suplemento hidroeletrolítico favorece reidratação e diminui proteinúria pós-treino em atletas karate

Abstract Introduction: Adequate hydration status in the sport is essential for good health, yet the relationship between hydration, proteinuria and sports is little studied. Objective: To analyze the influence of an isotonic sports drink as rehydration strategy on the hydration status and proteinuria after karate training. Methods: Ten athletes participated in this study. In the first session of standard training, called observation training session (STO), the athletes hydrated themselves according to their habits, and in the second session of standard training, called nutritional intervention training session (STIN), an ideal practice of hydration protocol was followed, using an isotonic sports drink as a rehydration liquid during the training. The hydration status was verified by monitoring the body weight before and after training, the urine specific gravity pre-and post-training and the urine volume post-training. To observe the influence of practice of hydration on the renal function post exercise proteinuria was measured. Results: We observed a statistically significant difference in urine density between the samples pre- and post-exercise only on STIN (p = 0.047). When we compare the sessions, there was a lower variation in body weight (p = 0.011) and higher urinary volume (p < 0.001), on nutritional intervention training. In STO, there was a higher percentage of athletes who showed proteinuria (70%) compared to the STIN (50%) in the urine sample after training. Conclusion: The use of isotonic sports drink as practice of hydration by karate athletes promoted rehydration during one session of training and reduce post-training proteinuria.

Resumo Introdução: Um adequado estado de hidratação durante a atividade esportiva é essencial para a manutenção da boa saúde, porém a relação entre hidratação, proteinúria e esportes é pouco estudada. Objetivo: analisar a influência de suplemento hidroeletrolítico (bebida esportiva isotônica) como estratégia de reidratação sobre o estado de hidratação e proteinúria após treino de Karate. Métodos: Dez atletas participaram deste estudo. Na primeira sessão de treino padronizado, denominada sessão de treino de observação (STO), os atletas se reidrataram segundo seus hábitos; na segunda sessão de treino padronizado, denominada sessão de treino de intervenção nutricional (STIN), foi seguido um protocolo ideal de prática de hidratação, utilizando-se de suplemento hidroeletrolítico como líquido reidratante durante o treino. O estado de hidratação foi verificado pelo monitoramento do peso corporal antes e após o treino, pela gravidade específica da urina pré e pós-treino e pelo volume urinário pós-treino. De forma a observar a influência da prática de hidratação sobre a função renal, a proteinúria pós-exercício foi medida. Resultados: Observou-se uma diferença estatisticamente significativa na densidade urinária entre as amostras coletadas pré e pós-exercício apenas na STIN (p = 0,047). Quando comparados entre sessões, houve menor variação ponderal (p = 0,011) e maior volume urinário (p < 0,001) no treino com intervenção nutricional. Na STO, houve um percentual mais elevado de atletas que apresentaram proteinúria (70%) em comparação a STIN (50%) na amostra de urina coletada após o treino. Conclusão: O uso de suplemento hidroeletrolitico como prática de hidratação por atletas de karate favoreceu a reidratação durante uma sessão de treino e reduziu a proteinúria pós-treino.

Association of proteinuria with various clinical findings and morphologic variables of oxford classification in immunoglobulin a nephropathy patients

Immunoglobulin A nephropathy [IgAN] with nephrotic syndrome is an uncommon form of IgAN. Clinical and morphological characteristics of proteinuria in IgAN, especially when is in nephrotic range have not yet been fully examined. This study was aimed to correlate morphologic variables of the Oxford classification, and various clinical data with proteinuria in IgAN patients. We also aimed to demonstrate the significance of prevention of proteinuria as one of the important factors in progression of this disease. In an observational study conducted on IgAN patients, total of 114 biopsies were entered in the study. IgAN was diagnosed by light and immunofluorescence study. Of 114 patients 70.2% were male. Mean age of patients was 37.7 +/- 13.6 years. The mean of proteinuria was 1742 +/- 1324 mg/day. Also mean of serum creatinine [Cr] was 1.6 +/- 1.5 mg/dL. Of 114 patients, 11[9.6%] had nephrotic range proteinuria. In this study, there was a positive correlation between proteinuria and serum Cr, peri-glomerular fibrosis or interstitial fibrosis. There was a positive association between proteinuria and totally sclerotic glomeruli too. There was also a positive association between the amount of fibrous crescents and the level of proteinuria. Nephrotic proteinuria could just be seen in male patients. Also, nephrotic syndrome had a positive association with the number of crescents. Our findings firstly support the prognostic value of crescent due to its association with proteinuria and secondly imply the importance of treatment of proteinuria to prevent progression of IgAN

Rosuvastatin prevents proteinuria and renal inflammation in nitric oxide-deficient rats

OBJECTIVE: The aim of the present study was to assess the effects of rosuvastatin on renal injury and inflammation in a model of nitric oxide deficiency. METHODS: Male Wistar rats were randomly divided into four groups (n = 10/group) and treated for 28 days with saline (CTRL); 30 mg/kg/day L-NAME (L-name); L-NAME and 20 mg/kg/day rosuvastatin (L-name+ROS-20); or L-NAME and 2 mg/kg/day rosuvastatin (L-name+ROS-2). Systolic blood pressure was measured by plethysmography in the central artery of the tail. The serum total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, nitric oxide, interleukin-6, and tumor necrosis factor alpha levels were analyzed. Urine samples were taken to measure the albumin: urinary creatinine ratio. Kidneys were sectioned and stained with hematoxylin/eosin and Masson's trichrome. Immunohistochemical analysis of the renal tissue was performed to detect macrophage infiltration of the glomeruli. RESULTS: The systolic blood pressure was elevated in the L-name but not the L-name+rosuvastatin-20 and L-name+rosuvastatin-2 groups. The L-name group had a significantly reduced nitric oxide level and an increased interleukin-6 and tumor necrosis factor alpha level, albumin: urinary creatinine ratio and number of macrophages in the renal glomeruli. Rosuvastatin increased the nitric oxide level in the L-name+rosuvastatin-2 group and reduced the interleukin-6 and tumor necrosis factor alpha levels, glomerular macrophage number and albumin:urinary creatinine ratio in the L-name+rosuvastatin-20 and L-name+rosuvastatin-2 groups. CONCLUSION: Rosuvastatin treatment reduced glomerular damage due to improvement in the inflammatory pattern independent of the systolic blood pressure and serum lipid level. These effects may lead to improvements in the treatment of kidney disease.

Recent update in the management of hypertension.

Hypertension is still the leading cause of death worldwide. Hypertension increases not only the risk for progression of chronic kidney disease (CKD) but also for cardiovascular (CV) morbidity and mortality. For most patients it is the systolic blood pressure rather than the diastolic blood pressure that most strongly predicts adverse events. The optimal target for BP control for most hypertensive patients is < 140/90 mmHg, or < 130/80 mmHg for patients with diabetes and CKD. Certain lifestyle measures such as weight reduction, smoking cessation, restriction of dietary sodium intake, moderation of alcohol intake and an increase in physical activity can lower BP. Except for progression of proteinuric kidney disease and congestive heart failure (CHF), it is the achieved BP and not the class of agent that is most important in reducing morbid outcomes. If BP is more than 20/10 mmHg above the goal, therapy should be initiated with 2 drugs, one of which should be a thiazide-type diuretic. A strong consideration should be given to initiate antihypertensive therapy in patients with (RAAS) blockers, usually in concert with diuretics. Patients with proteinuria > 1 g/day despite optimal BP control with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) monotherapy may benefit from a combination therapy.

Proposta de padronização de um programa de rastreamento da doença renal crônica / Suggestion of standardization of a screening program for chronic kidney disease

Até recentemente, a prevalência da doença renal crônica (DRC) foi amplamente subestimada. A partir do final do século passado, estudos populacionaisnos Estados Unidos da América, Europa e Oceania revelaram que a prevalência da DRC é mais elevada do que se pensava anteriormente. Tragicamente,a maior parte destes pacientes morre de causas cardiovasculares antes de atingirem o estágio de falência funcional renal. Os dados existentes no Brasilsobre DRC são eminentemente baseados em levantamentos realizados em unidades de diálise. Nossas campanhas de prevenção ainda são realizadas àcusta de esforços individuais, com pouco ou nenhum apoio do poder público, de modo que, embora por vezes atinjam grande número de pessoas, aindageram pouca informação sobre DRC em nosso meio. Neste artigo, os autores apresentam uma proposta de abordagem simples para a identificaçãoprecoce da DRC. Propõem dois fluxogramas de rastreamento das doenças renais, um baseado na proteinúria e outro baseado inicialmente na estimativada filtração glomerular a partir da creatinina e, nas etapas seguintes, orientado pela proteinúria. Chamam a atenção para a necessidade de se gerarinformações mais confiáveis sobre a doença através da uniformização das coletas de dados, assim atraindo a atenção de outros especialistas,particularmente os clínicos gerais, cardiologistas e endocrinologistas, para com isso engajá-los no manejo da DRC.

Until recently, the prevalence of chronic kidney disease (CKD) was widely neglected. However, community based studies done in United States of Ameri -ca, Europe, and Oceania at the end of the last century showed that CKD was more previsously thought. Tragically, most patients with CKD die before theyreach end stage renal failure. So far, in Brazil, the data about CKD, relies mainly on surveys made in dialysis units. Our prevention campaigns are donebased on individual endeavors, generally with little or no support from the public power. As a consequence, a large number of people are screened, although little is still known about the prevalence of CKD. In this review paper, the authors present a proposal to approach, in a simple way, the identification of CKD.It is presented two diagrams to screen for renal diseases, one based on proteinuria and the other starting from glomerular filtration rate estimated from serum creatinine, and then by proteinuria. Although the eventual limitations that any screening program for CKD might have, it is imperative that we standardize the tests for the obtainment of more reliable data, and, thus, to attract more attention for the disease among the other specialists, in order to engage them in the management of the disease.

Otimização da prevenção da doença renal crônica / Optimizing chronic kidney disease prevention

A intervenção no ritmo da progressão da doença renal crônica (DRC) é uma realidade na atualidade. A identificação precoce de pacientes em risco dedesenvolver DRC possibilita intervenções que evitam o aparecimento da doença renal em um grande número de indivíduos. Reconhecidamentehipertensão arterial e Diabetes mellitus são as doenças que respondem pela maioria dos pacientes que evoluem com DRC atualmente. A identificaçãoprecoce e rotineira do comprometimento renal se faz necessária através de testes simples como pesquisa de proteinúria e, estimativa da filtraçãoglomerular através da creatinina plasmática. Uma vez que as principais causas de DRC são doenças acompanhadas por diferentes especialistas e onúmero de pacientes é alto, torna-se de fundamental importância que médicos encarregados da atenção primária à saúde, cardiologistas eendocrinologistas estejam atentos a este fato e que se comprometam com a prevenção da doença renal realizando pesquisa rotineira da função renal eencaminhando os pacientes para diagnóstico definitivo da disfunção renal, quando necessário, ao especialista. Propomos, portanto, que todos os médicosenvolvidos com populações de risco devem estar cientes da necessidade de investigação periódica da função renal, bem como estar atentos para atingiras metas estipuladas para o tratamento preventivo, especialmente quanto à proteinúria, glicemia e a hipertensão arterial.

The possibility of modifying the progression of chronic kidney disease (CKD) is a reality nowadays. Early identification of patients at high risk for CKD makes possible to avoid the development of the disease in a great number of subjects. It is well known that arterial hypertension and diabetes mellitus are the maincauses of CKD in the present days. The early and routinely identification of renal damage, in this population is necessary and can be done through simple tests as proteinuria and estimation of glomerular filtration rate using serum creatinine. Since baseline diseases for CKD are treated by different specialistsand the number of patients is high, primary care physicians, cardiologists and endocrinologists must be aware about CKD prevention. We propose there -fore that physicians directly involved with high risk populations should be able to investigate renal function periodically, as well as to achieve guideline-re -commended targets for these patients concerning proteinuria, glycemia, and arterial hipertension.

Angiotensin II antagonists: clinical experience in the treatment of hypertension, prevention of cardiovascular outcomes and renal protection in diabetic nephropathy and proteinuria / Antagonistas da angiotensina II: experiência clínica com o tratamento da hipertensão, prevenção de desfechos cardiovasculares e proteção renal na nefropatia diabética e proteinúria

Angiotensin II antagonists (AIIAs) were introduced to treat hypertension about 10 years ago. During this period they were evaluated not only in terms of efficacy and safety but also in several large studies with clinical outcomes. They are efficacious in all clinical forms of hypertension and are effective also in all ethnic groups. Cardiovascular and renal protection in proteinuric diabetic nephropathy beyond blood pressure reduction was proved in major clinical studies: Losartan Intervention For Endpoint reduction in hypertension study (LIFE), Reduction of Endpoint in Non-Insulin dependent Diabetes Mellitus with the AII Antagonist Losartan (RENAAL) and Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT). Their blood pressure independent protective effect is also mentioned by the blockade of AT1 receptor. As a class AIIs have a tolerability profile similar to placebo.

Os antagonistas da angiotensina II (AAIIs) foram introduzidos para o tratamento da hipertensão arterial há cerca de 10 anos. Durante esse período eles foram avaliados não apenas em termos de eficácia e segurança, mas também em vários estudos grandes com desfechos clínicos. Os AAIIs são eficazes em todas as formas clínicas de hipertensão e, também, em todos os grupos étnicos. Os principais estudos clínicos em pacientes diabéticos com nefropatia e proteinúia comprovaram, além da redução da pressão arterial, proteção cardiovascular e renal: "Losartan Intervention For Endpoint reduction in hypertension study" (LIFE), "Reduction of Endpoint in Non-Insulin dependent Diabetes Mellitus with the AII Antagonist Losartan" (RENAAL) e "Irbesartan Type 2 Diabetic Nephropathy Trial" (IDNT). O seu efeito protetor independente da pressão sanguínea também é mencionado pelo bloqueio do receptor AT1. Os AAIIs, como classe medicamentosa, apresentam um perfil de tolerabilidade semelhante ao placebo.

Effect of oral magnesium supplementation on experimental pre-eclampsia induced by prolonged blockade of nitric oxide synthesis in pregnant rats.

Nitric oxide inhibitor L-NAME when given alone caused a significant rise in both systolic and diastolic pressure, an increase in 24 hr urinary protein excretion and reduction in weight of the litter as compared to control group. Supplementation of MgSO4 at lower dose (250 mg/kg) did not inhibit this pre-eclamptic effect of L-NAME; but in higher doses (500 and 750 mg/kg), it inhibited the pre-eclamptic action of L-NAME. The results suggest that administration of MgSO4 improves the foetal outcome and significantly prevents the development of symptoms of pre-eclampsia like hypertension and proteinuria.

Proteinuria in essential hypertension.

Porteinuria was quantitatively measured in twenty-five controls and eighty-one newly detected patients of essential hypertension without renal insufficiency. Hypertension was treated with enalapril, enalapril and nifedepine and nifedepine alone. Mean proteinuria was more in patients of hypertension as compared to controls (P < .001). Proteinuria decreased significantly (P < .001) after six weeks of control of hypertension. Patients treated with enalapril alone had maximum reduction in proteinuria than those with enalapril and nifedepine, and nifedepine alone.

Effect of cicletanine on the progression of chronic renal failure in rats

1. The effects of chronically administered cicletanine (CICL), an antihypertensive and prostacyclin stimulating agent, on glomerular hemodynamics were evaluated after 30 (CRF-30) or 60 (CRF-60) days of chronic renal failure (CRF) induced by 5/6 nephrectomy in Munich-Wistar rats. 2. CICL administration (3 mg kg-1 day-1, N = 5) for 60 days did not modify glomerular hemodynamics of normal rats (control group). The CRF-60 group (N = 6) presented a significant increase in mean arterial pressure (MAP) compared with control (122 +/- 7 vs 98 +/- 2 mmHg, P < 0.05), which was attenuated by CICL (113 +/- 7 vs 122 +/- 7 mmHg). 3. Hyperfiltration and hyperperfusion were observed in both CRF groups after 30 (N = 5) but not after 60 days of CRF, 73.9 +/- 6.3 and 48.2 +/- 3.2 vs 36.8 +/- 2.6 nl/min for SNGFR and 200 +/- 17 and 147 +/- 8 vs 112 +/- 8 nl/min for QA in CRF-30, CRF-60 vs control group, respectively. However, glomerular hypertension was demonstrable for both CRF groups only after 60 days. CICL treatment starting 7 days prior to nephrectomy reduced the transcapillary hydraulic pressure difference (delta P) in both groups, 36 +/- 3 vs 30 +/- 2 mmHg (30 days) and 41 +/- 4 vs 34 +/- 2 (60 days), but did not significantly modify arteriolar resistances or glomerular hemodynamics, suggesting that the reduction in MAP in response to CICL may have been responsible for the decrease in delta P. CICL administration did not prevent the proteinuria or glomerular sclerosis associated with CRF. 4. The results suggest that the administration of CICL for 30 (N = 4) to 60 days (N = 7) was sufficient to prevent systemic hypertension associated with CRF but not to reduce the additional glomerular hemodynamic factors that participate in the progression of CRF