Mauricio Younes-Ibrahim

Epidemiology of Acute Kidney Injury in Latin America

There is little reliable information on the epidemiology of acute kidney injury (AKI) in Latin America. It is generally assumed that AKI in the developing world affects mainly young and previously healthy people, with an etiologic spectrum relying on particular socioeconomic and environmental conditions. Transmissible diseases such as leptospirosis, malaria, dengue, diarrhea, among others, are recognized as important causes of AKI in these areas. On the other hand, in large cities and university hospitals in Latin American, the AKI spectrum is similar to that seen in developed countries. Large studies are needed to improve our knowledge to design preventive strategies for this potentially lethal disease that affects all population subgroups, from the socially and economically vulnerable to the wealthy. In this article the available information regarding AKI epidemiology in Latin America is reviewed. Data obtained by the Latin American Acute Renal Failure Commission from the Latin American Society of Nephrology through surveys performed in 1997, 2000, and 2004 are reported. Finally, 3 particular medical conditions frequently associated with AKI in Latin America are reviewed.

Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor

BackgroundLeptospiral glycolipoprotein (GLP) is a potent and specific Na/K-ATPase inhibitor. Severe pulmonary form of leptospirosis is characterized by edema, inflammation and intra-alveolar hemorrhage having a dismal prognosis. Resolution of edema and inflammation determines the outcome of lung injury. Na/K-ATPase activity is responsible for edema clearance. This enzyme works as a cell receptor that triggers activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathway. Therefore, injection of GLP into lungs induces injury by triggering inflammation.MethodsWe injected GLP and ouabain, into mice lungs and compared their effects. Bronchoalveolar lavage fluid (BALF) was collected for cell and lipid body counting and measurement of protein and lipid mediators (PGE2 and LTB4). The levels of the IL-6, TNFα, IL-1B and MIP-1α were also quantified. Lung images illustrate the injury and whole-body plethysmography was performed to assay lung function. We used Toll-like receptor 4 (TLR4) knockout mice to evaluate leptospiral GLP-induced lung injury. Na/K-ATPase activity was determined in lung cells by nonradioactive rubidium incorporation. We analyzed MAPK p38 activation in lung and in epithelial and endothelial cells.ResultsLeptospiral GLP and ouabain induced lung edema, cell migration and activation, production of lipid mediators and cytokines and hemorrhage. They induced lung function alterations and inhibited rubidium incorporation. Using TLR4 knockout mice, we showed that the GLP action was not dependent on TLR4 activation. GLP activated of p38 and enhanced cytokine production in cell cultures which was reversed by a selective p38 inhibitor.ConclusionsGLP and ouabain induced lung injury, as evidenced by increased lung inflammation and hemorrhage. To our knowledge, this is the first report showing GLP induces lung injury. GLP and ouabain are Na/K-ATPase targets, triggering intracellular signaling pathways. We showed p38 activation by GLP-induced lung injury, which was may be linked to Na/K-ATPase inhibition. Lung inflammation induced by GLP was not dependent on TLR4 activation.

Na/K-ATPase assay in the intact guinea pig liver submitted to in situ perfusion.

We describe an assay for the enzyme Na/K-ATPase in intact guinea pig livers perfused through the portal vein with modified Hanks solution. The model uses the measurement of non-radioactive rubidium ion incorporation by liver cells, both in the absence and in the presence of the specific Na/K-ATPase inhibitor ouabain, followed by a rinsing procedure with cold saline. The concentration of Rb+ in acid-digested liver lobes was measured by atomic emission spectrometry and Na/K pump activity was calculated by the difference between the incorporation of Rb+ in the absence and in the presence of ouabain. The optimal conditions for Rb+ incorporation were: perfusion flow rate, 3 ml/min per liver; perfusion time at 37 degrees C, 60 min; rinsing time with cold saline, 5-10 min; and concentration of ouabain, 3 mM. The calculated ouabain IC(50) was 100 microM. The major advantage of this model is the possibility of testing experimental drugs affecting this enzyme in conditions close to those in the intact organ.

Na/K-ATPase assay in the intact mice lung subjected to perfusion

BackgroundAmong the characteristics of acute respiratory distress syndrome (ARDS) is edema formation and its resolution depends on pneumocyte Na/K-ATPase activity. Increased concentration of oleic acid (OA) in plasma induces lung injury by targeting Na/K-ATPase and, thus, interfering in sodium transport.FindingsPresently, we adapted a radioactivity-free assay to detect Na/K-ATPase activity in perfused lung mice, comparing the inhibitory effect of ouabain and OA. We managed to perfuse only the lung, avoiding the systemic loss of rubidium. Rb+ incorporation into lung was measured by inductively coupled plasma optical emission spectrometry (ICP OES) technique, after lung tissue digestion. Na/K-ATPase activity was the difference between Rb+ incorporation with or without ouabain. Lung Na/K-ATPase was completely inhibited by perfusion with ouabain. However, OA caused a partial inhibition.ConclusionsIn the present work the amount of incorporated Rb+ was greater than seen in our previous report, showing that the present technique is trustworthy. This new proposed assay may allow researchers to study the importance of Na/K-ATPase activity in lung pathophysiology.

Mesangial cells: renal function protagonists or coadjuvants?

Para realizar a homeostasia, cada rim possui cerca de 1 milhao de nefrons, que por sua vez, sao compostos de diferentes tipos de celulas e tecidos. A harmonia funcional entre as celulas do parenquima renal depende de uma sofisticada rede de bioautomacao para assegurar a hierarquia e a efetividade das respostas biologicas integradas. Descritas desde meados do seculo XIX, as celulas mesangiais (CM) e a matriz mesangial formam a regiao glomerular denominada mesangium (entre vasos). Analisadas pela simplicidade da microscopia [...]

Brazilian Nephrology pays homage to Peter Brian Medawar

Em 28 de fevereiro de 2015, celebramos o centenario do nascimento de Peter Brian Medawar, brasileiro nato, que se tornou um dos maiores cientistas do seculo XX e foi agraciado com o premio Nobel de Medicina, em 1960. Peter nasceu em Petropolis, estado do Rio de Janeiro, fato que lhe conferiu cidadania brasileira. Seu pai, Name Medawar, libanes maronita, fez fortuna na Inglaterra fabricando instrumentos odontologicos e opticos. Sua mae, a inglesa Edith Muriel Dowling, veio com o marido para [...]

Maternal High Sodium Diet Yields Kidney Alterations in Mice Offspring

Background-Aims : We aimed to examine the effects of a maternal high-sodium diet in the kidney and blood pressure (BP) of the offspring. Materials and Methods : Beginning eight weeks before pregnancy, female mice received a diet containing either 0.25% sodium chloride (NaCl) - (standard chow, SC) or 4.0% NaCl (high-sodium, HS). Females were mated with male mice fed a SC diet. Their offspring were analyzed at three different ages: at birth, at day 10, and at three months. Results : Before mating, HS dams exhibited higher corticosterone levels and higher BP than the SC dams. At birth, neonatal mortality was higher in the offspring of HS dams than in those from SC dams. At three months of age, HS offspring compared to SC offspring, showed higher proteinuria and BP, greater glomerular sclerosis, and lower creatinine clearance, blood urea nitrogen clearance, and glomerular filtration rate. The fractional excretions of sodium, potassium, urea, and the protein expressions of the renin-angiotensin system (RAS) were higher in HS than in SC offspring, but AT2R, Wilms’ tumor suppressor gene (WT)1 and podocin were lower in HS than in SC offspring. Conclusion : The offspring exposed to a maternal diet with high sodium content shows glomerular sclerosis with consequent high blood pressure and a shift in the renal expression of proteins (WT1, podocin, and RAS) at maturity. Consequently, the renal function of the offspring deteriorates more quickly than offspring from mothers fed a standard sodium diet.