Caracterización de las complicaciones renales en pacientes con anemia de células falciformes / Characterization of kidney complications in patients with sickle cell anemia

Resumen: Introducción: La nefropatía falciforme (NF) es una complicación poco estudiada en la edad pediátrica, que se manifiesta en diferentes formas, incluyendo la glomerulopatía y la tubulopatía. Objetivo: Descri bir las complicaciones renales agudas y crónicas de niños con anemia de células falciformes (ACF). Pacientes y Método: Estudio de cohorte restrospectiva. Se incluyeron pacientes pediátricos con diagnóstico confirmado de enfermedad de células falciformes que tuvieran estudio nefro-urológico. Se consignó patrón electroforético de hemoglobina, presencia y tipo de afectación renal, y presencia de compromiso cardiológico. Se realizó análisis bivariado para comparar pacientes con y sin NF. Resultados: Se incluyeron 79 pacientes, 59.5% hombres, siendo el patrón electroforético más fre cuente Hb-SS (60.9%). La NF se presentó en el 70% de ellos, con una edad de 114 meses (RIQ 65-157). Las alteraciones más frecuentemente encontradas fueron hiperfiltración glomerular, mi croalbuminuria, lesión renal aguda, hipertensión arterial e hipostenuria. En el análisis bivariado, un ecocardiograma anormal fue más frecuente en los pacientes con NF (84,8% vs 54,3% p = 0,01), así como tuvieron una tendencia a mayor uso de medicamentos nefrotóxicos (74,5% vs 54,2% p = 0,07). Conclusiones: Nuestros hallazgos sugieren que la nefropatía falciforme puede presentarse a tempra na edad, siendo muy frecuente la hiperfiltración glomerular. Las complicaciones cardiopulmonares en ACF se podrían asociar con la presencia NF.

Abstract: Introduction: Sickle cell nephropathy (SCN) is a poorly studied complication of pediatric patients. It appears in different forms, including glomerulopathy, and tubulopathies. Objective: To describe acute and chronic renal complications in patients with sickle cell anemia (SCA). Patients and Method: Re trospective study. Pediatric patients with confirmed diagnosis of sickle cell disease were included who had a nephro-urology study. Hemoglobin electrophoresis pattern, presence and type of renal involvement, and presence of cardiac involvement were recorded. Bivariate analysis was perfor med to compare patients with and without SCN. Results: 79 patients were included, 59.5% of them were men, and the most frequent electrophoresis pattern was Hb-SS (60.9%). The SCN oc curred in 70% of patients with an average age of 114 months (RIQ 65-157). The most frequently observed alterations were glomerular hyperfiltration, microalbuminuria, acute kidney injury, ar terial hypertension, and hyposthenuria. In the bivariate analysis, an abnormal echocardiogram result was presented more frequently in patients with SCN (84.8% vs. 54.3% p = 0.01), as well as more frequent use of nephrotoxic drugs (74.5% vs. 54.2% p = 0.07). Conclusions: Our findings suggest that sickle cell nephropathy may occur at an early age, where glomerular hyperfiltration is very common. Cardiopulmonary complications in patients with SCA may be related to the presence of SCN.

Intercellular mediators in bone remodeling regulation in the experimental renal pathology / Mediadores intercelulares de la regulación de la remodelación ósea en un modelo experimental de patología renal

Bone metabolism disorders are characterized by an imbalance of bone resorption and formation in the bone remodeling process. Glucocorticoids that are used to treat kidney diseases exacerbate these disorders. P-selectin and galectin-3 are molecules involved in the sclerotic process in kidney, whereas bone resorption is regulated by the interaction between the nuclear factor activator kappa b receptor (RANK), its ligand (RANKL) and the RANKL decoy receptor osteoprotegerin (OPG). The aim of this study was to investigate the cellular and molecular mechanisms of disruption of bone remodeling regulation processes, reflected by intercellular mediators (RANKL, OPG, P-selectin and galectin-3) in chronic kidney disease experimental model treated with glucocorticoids. Rats were divided into four groups of 10 animals each. The first group, the control group, included intact animals. The second group consisted of rats with impaired bone remodeling resulting from chronic kidney disease (experimental group (CKD). The third group was a group of animals with impaired bone remodeling due to exposure to glucocorticoids (experimental group (GCs)). The fourth group consisted of rats with impaired bone remodeling in chronic kidney disease, followed by exposure to glucocorticoids (experimental group (CKD + GCs)). The effects of CKD and glucocorticoid were evaluated biochemically, histologically and by measuring bone density. An enzymelinked immunoassay was used to measure intercellular mediator levels in the serum. The bone density in the experimental groups was reduced compared to the control group. RANKL levels in animals of three experimental groups were higher than in intact animals. Serum levels of OPG were higher in CKD and GCs groups than in intact animals. At the same time, in the animals' blood serum of the CKD + GCs group, the levels of OPG were lower, than those in animals from the control group. The levels of galectin-3 in the serum of the experimental groups GCs and CKD + GCs were lower than in intact animals. The serum levels of galectin-3 in animals of the CKD group were higher than those in animals from the control group. The levels of P-selectin were lower in the serum of the GCs group than in intact animals. At the same time, the levels of P-selectin were higher in the CKD and CKD + GCs groups, than those in animals from the control group. In conclusion, the study of the complex system of bone remodeling regulation, which includes many factors and their interactions, may lead to the development of new methods for treating patients with chronic kidney disease in order to prevent osteoporosis in the future. (AU)

Las enfermedades metabólicas óseas se caracterizan por un desequilibrio en el proceso de remodelación ósea en los que participan mediadores tales como receptor del activador del factor nuclear- kappa- b (RANK), su ligando (RANKL) y la osteoprotegerina (OPG). Los glucocorticoides, recuentemente empleados en el tratamiento de la enfermedad renal crónica, exacerban este desequilibrio. En la enfermedad esclerótica renal, las moléculas de adhesión celular P-selectina and galectina-3 tienen un rol fundamental. El objetivo de esta trabajo fue estudiar las alteraciones en los mediadores de la remodelación ósea (RANKL, OPG, P-selectina and galectina-3) en un modelo de enfermedad renal crónica con tratamiento glucocorticoideo. Ratas Wistar hembras fueron divididos en 4 grupos: control (C); enfermedad renal crónica con afección de la remodelación ósea (ERC); animales con afección de la remodelación ósea expuestos a glucocorticoides (GC); enfermedad renal crónica con afección de la remodelación ósea tratados con glucocorticoides (ERC+GC). Los efectos de la ERC y los GC fueron evaluados bioquímicamente, histológicamente y por medición de la densidad ósea. RANKL, OPG, Pselectina and galectina-3 se cuantificaron en muestras de sangre venosa empleando enzimoinmuno análisis. En los 3 grupos experimentales la densidad ósea se evidenció reducida y los niveles séricos de RANKL elevados respecto al grupo control. Los niveles de OPG en los grupos ERC y GC fueron superiores mientras que en el grupo ERC+GC menores respecto a los animales controles. Galectina 3 plasmática en GC y ERC+GC se encontró reducida y aumentada en los animales ERC, en comparación con los animales controles. La concentración sérica de P-selectina sérica fue mayor en los grupos ERC y ERC+GC, y menor en los animales GC respecto a los niveles plasmáticos de los animales intactos. El avance del conocimiento sobre la regulación de la remodelación ósea a través de la interacción de mediadores sistémicos, en un futuro, puede conducir al desarrollo de nuevas estrategias terapéuticas para la prevención de la osteoporosis en pacientes con enfermedad renal crónica. (AU)

Association between syndecan-1 and renal function in adolescents with excess weight: evidence of subclinical kidney disease and endothelial dysfunction

Excess weight (overweight and obesity) is associated with kidney and cardiovascular disease. The aim of this study was to investigate the association between syndecan-1 and renal function among adolescents with excess weight. A total of 56 students from a public school at Fortaleza, CE, Brazil, were investigated. The adolescents were submitted to anthropometric evaluation, including weight, height, blood pressure and body mass index. Blood and urine samples were collected for the determination of serum lipids (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides), and the endothelial injury biomarker syndecan-1. Participants' mean age was 16±1 years (range 14-19 years), and 68% were females. Overweight was observed in 4 cases (7.1%) and obesity in 7 (12.5%). Changes in serum lipid levels were more frequent in the overweight group. A positive correlation between syndecan-1 and serum creatinine (r=0.5, P=0.001) and triglycerides (r=0.37, P=0.004), and a negative correlation with glomerular filtration rate (r=-0.33, P=0.02) were found. These findings suggest that adolescents with excess weight present incipient changes at the cellular level that make them more vulnerable to the development of kidney and cardiovascular diseases.

Aspectos clínicos, fisiopatológicos e genéticos das tubulopatias hereditárias na infância / Clinical, pathophysiological and genetic aspects of inherited tubular disorders in childhood

ResumoNesta revisão, descrevemos a função tubular de cada segmento do néfron seguida das descrições das principais alterações moleculares que possam ocorrer nos transportadores expressos nestes locais. Assim, o conhecimento das modificações na função tubular renal permite o entendimento e o reconhecimento clínico das doenças tubulares renais que podem causar a morte fetal, neonatal ou infantil. Além disso, as crianças com tubulopatias podem evoluir para doença renal crônica terminal numa fase precoce da vida e também podem apresentar distúrbios do crescimento e do desenvolvimento acompanhados ou não de alterações neurológicas. Então, nós utilizamos o unitermo "inherited tubular disorders" a fim de selecionar na base de dados do PubMed os estudos publicados desde 2006. Esperamos que a leitura desta revisão auxilie no rápido diagnóstico dos pacientes com tubulopatias, o que poderá permitir o tratamento especializado e a possível melhora do prognóstico e qualidade de vida destes indivíduos.

AbstractIn this review, we described the tubular function of each nephron segment followed by the most important changes that may occur in the transporters expressed therein. Thus, knowledge of the changes in renal tubular function allows the understanding and recognition of renal tubular diseases that can cause stillbirth or death in newborns or in childhood. Moreover, children with tubular disorders may progress to chronic renal disease at an early stage of life and they may also show disturbances of growth and development associate or not with neurological dysfunction. Therefore, we used the keyword "inherited tubular disorders" to select the children studies that have been published in the PubMed database since 2006. We hope that this review may help physicians to perform an early diagnosis in patients with tubular disorders allowing a specialized treatment and an improvement in their prognosis and quality of life.

Denervação simpática renal em pacientes com cardiodesfibrilador implantável e tempestade elétrica / Renal sympathetic denervation in patients with implantable cardioverter-defibrillator and electrical storm

Introdução: Cardiodesfibriladores implantáveis (CDIs) são geralmente indicados para pacientes com arritmias malignas considerados de alto risco. A hiperatividade simpática desempenha um papel crítico no desenvolvimento, na manutenção e no agravamento de arritmias ventriculares. Novas opçõesde tratamento nessa população representam uma necessidade clínica. Nosso objetivo foi relatar osresultados de pacientes com CDIs e tempestade elétrica submetidos à denervação simpática renal paracontrole da arritmia. Métodos: Oito pacientes com CDIs internados por tempestade elétrica refratária ao tratamento médico otimizado foram submetidos à denervação simpática renal. Condições subjacentes foram: doença de Chagas (n = 6), cardiomiopatia dilatada não isquêmica (n = 1) e cardiomiopatia isquêmica (n = 1). As informações sobre o número de taquicardias ventriculares/fibrilações ventriculares e episódios de terapiasantitaquicardia na última semana pré-procedimento e nos 30 dias pós-tratamento foram obtidas por meiode interrogação dos CDIs. Resultados: As medianas dos episódios de taquicardias ventriculares/fibrilações ventriculares, sobreestimulaçãoe choques na semana que antecedeu a denervação simpática renal foram de 29 (9 a 106), 23 (2 a 94) e 7,5 (1 a 88), sendo significativamente reduzidas para 0 (0 a 12), 0 (0 a 30) e 0 (0 a 1), respectivamente, 1 mês após o procedimento (p = 0,002; p = 0,01; p = 0,003). Nenhum paciente morreu durante o acompanhamento. Não ocorreram complicações maiores relacionadas ao procedimento.Conclusões: Em pacientes com CDIs e tempestade elétrica refratária ao tratamento médico otimizado, a denervação simpática renal reduziu significativamente a carga de arritmia e, consequentemente, as sobre-estimulações e os choques. Ensaios clínicos randomizados, no contexto de denervação simpática renal para controle de arritmias cardíacas refratárias, são necessários para trazer maior robustez aos nossos achados.

Background: Implantable cardioverter-defibrillators (ICDs) are usually indicated for patients with malignant arrhythmias considered as high risk. Sympathetic hyperactivity plays a critical role in thedevelopment, maintenance, and worsening of ventricular arrhythmias. New treatment options in thispopulation represent a clinical necessity. This study's objective was to report the outcomes of patients with ICDs and electrical storm submitted to renal sympathetic denervation for arrhythmia control. Methods: Eight patients with ICDs admitted for electrical storm refractory to optimal medical therapy underwent renal sympathetic denervation. Underlying diseases included Chagas disease (n = 6), non-ischemic dilated cardiomyopathy (n = 1), and ischemic cardiomyopathy (n = 1).Information on the number of episodes of ventricular tachycardia/ventricular fibrillation and antitachycardia therapies in the week before the procedure and 30 days after treatment were obtained through interrogation of the ICDs.Results: The median numbers of episodes of ventricular achycardia/ ventricular fibrillation,antitachycardia pacing, and shocks in the week before renal sympathetic denervation were 29 (9 to 106), 23 (2 to 94), and 7.5 (1 to 88), and significantly reduced to 0 (0 to 12), 0 (0 to 30), and 0 (0 to 1), respectively, 1 month after the procedure (p = 0.002; p = 0.01; p = 0.003, respectively). No patients diedduring follow-up. There were no major complications related to the procedure.Conclusions: In patients with ICDs and electrical storm refractory to optimal medical treatment, renal sympathetic denervation significantly reduced arrhythmia load and, consequently, antitachycardia pacing and shocks. Randomized clinical trials in the context of renal sympathetic denervation tocontrol refractory cardiac arrhythmias are needed to further support these findings.

El litio y su relación con la acuaporina-2 y el canal de sodio ENaC / Lithium and its relation with the epithelial sodium channel and aquaporin-2

Desde hace más de cuarenta años que el litio es usado para el tratamiento de la enfermedad bipolar; recientes estudios sugieren también su utilidad en el trastorno cognitivo mínimo tipo amnésico. El litio es filtrado en el glomérulo y un 65-75% del mismo es reabsorbido en el túbulo contorneado proximal y en el asa ascendente de Henle por el transportador Na+, K+, 2Cl- y vía paracelular. Una pequeña fracción del litio entra en las células principales del túbulo colector por medio del canal epitelial de sodio sensible al amiloride (ENaC) localizado en la membrana apical de la célula. Luego de 10- 20 años de tratamiento con litio los enfermos pueden desarrollar poliuria, acidosis tubular e insuficiencia renal crónica que puede terminar en una forma de diabetes que no responde a la arginina vasopresina llamada diabetes insípida nefrogénica. Se cree que estas fallas renales son consecuencias de una reducción en el número de moléculas de acuaporina 2 en la membrana apical. Las causas para esto son complejas. El litio es un poderoso inhibidor de la isoforma beta de la enzima glicógeno sintetasa quinasa y esto está asociado a una menor actividad de la adenilato ciclasa que lleva a una disminución en la concentración intracelular de cAMP. Esto finalmente interferiría con la síntesis de nuevas moléculas de acuaporina 2 y con el tráfico de ellas desde la zona subapical de la célula hacia la membrana celular, causando la disminución en la reabsorción de agua en la parte distal del nefrón.

For more than 40 years lithium has been used to treat bipolar disorder and recent trials suggest a potential efficacy also in the treatment of the amnestic mild cognitive impairment. Lithium is filtered by the glomerulus and 65% - 75% of the filtered amount is reabsorbed along the proximal tubule and in the thick ascending limb of Henle's loop by the Na+, K+, 2Cl- transporter and via paracellular. A small fraction of lithium is reabsorbed in the collecting duct's principal cells through the epithelial Na channel (ENaC) located on the apical side of the cells. Polyuria, renal tubular acidosis and chronic renal failure are the most frequent adverse effects of lithium after 10-20 years of treatment and these alterations can reach to a vasopressin nonresponding form of diabetes insipidus entity called nephrogenic diabetes insipidus. It is believed that the molecular mechanisms of these renal changes are related to a reduction in the number of aquaporin-2 inserted in the apical membrane of the cells. The causes of this are complex. Lithium is a powerful inhibitor of the enzyme glycogen synthase kinase 3β and this is associated with a lower activity of adenylate cyclase with a reduction in the cAMP levels inside of the cells. The latter may interfere with the synthesis of aquaporin-2 and also with the traffic of these molecules from the subapical site to membrane promoting the impairment of water reabsorption in the distal part of the kidney.

Comparación entre las ecuaciones CKD-EPI y MDRD para la estimación del filtrado glomerular en pacientes con enfermedad renal crónica / Comparison between CKD-EPI and MDRD-equations to estimate glomerular filtration rate in chronic kidney disease patients

La ecuación MDRD para la estimación del índice de filtrado glomerular (IFG), es la estrategia más utilizada para evaluar pacientes con enfermedad renal crónica (ERC). Sin embargo, puede subestimar el IFG con el riesgo de asignar al paciente a estadios más avanzados de ERC. La nueva ecuación CKD-EPI, mejoraría la exactitud y precisión de las estimaciones. Sus autores sugieren que reemplace a la anterior. No habiendo comparaciones de estas ecuaciones aplicadas en un gran número de pacientes en nuestro país, nuestro objetivo fue realizarla en una amplia cohorte de pacientes. Se evaluó la concordancia de asignación en estadios de ERC entre ambas ecuaciones, tomando como referencia los datos surgidos de MDRD. Se calculó la media de las diferencias de los IFG obtenidos empleando ambas ecuaciones y se aplicó el análisis estadístico de Bland-Altman. Se estudió una cohorte de 9 319 pacientes con una media de creatinina sérica de 1.60 ± 1.03 mg/dl, 67% de sexo femenino y edad media 58 ± 20 años. En el grupo total, CKD-EPI presentó una media de IFG 0.61 ml/min/1.73 m² mayor que MDRD (p: NS). En los estadios 2 y 3A las medias del IFG fueron respectivamente 6.95 ± 4.76 y 3.21 ± 3.31, y la concordancia de 81 y 74%. El porcentaje de pacientes con un IFG menor de 60 ml/min/1.73 m², se redujo de 76.3% (MDRD) a 70.1% (CKD-EPI). Por lo tanto, la nueva ecuación CKD-EPI disminuye el número de pacientes con IFG debajo de 60 ml/min/1.73 m² y asigna estadios de IFG más elevado a un número mayor de pacientes.

The MDRD equation to estimate glomerular filtration rate (GFR) is the most widely used strategy to assess chronic kidney disease. Nonetheless, for the individual patient the true GFR can be underestimated with the risk of diagnosing a more elevated CKD stage. This novel CKD-EPI equation would improve accuracy and precision of estimations, and several authors recommend this new equation replace the former. In our country there is only a limited registration of these comparisons performed on a large number of patients. Therefore, our aim was to develop a comparison in a wide cohort of patients. The concordance between both equations to assign the GFR stages was determined by using the MDRD formula as a reference. The mean difference of GFR obtained with both equations as well as the Bland-Altman analysis were calculated. A cohort of 9 319 individuals, of whom 67% were females, aged 58 ± 20 years, with serum creatinine values of 1.6 ± 1.03 mg/dl, was studied. In the whole group, CKD-EPI displayed an average GFR 0.61 ml/min/1.73 m² larger than MDRD (p: NS). For CKD stages 2 and 3A the mean estimated GFR difference was 6.95 ± 4.76 and 3.21 ± 3.31, while the concordance was 81 and 74% respectively. The percentage of patients with GFR < 60 ml/min/1.73 m², decreased from 76.3% with the former equation to 70.1% with the latter. The novel equation CKD-EPI reduces the number of patients with GFR values lower than 60 ml/min/1.73 m² and consequently assigns a higher GFR stage to a considerable quantity of individuals.

Repercussão de um protocolo fisioterapêutico intradialítico na funcionalidade pulmonar, força de preensão manual e qualidade de vida de pacientes renais crônicos / Repercussion of physiotherapy intradialytic protocol for respiratory muscle function, grip strength and quality of life of patients with chronic renal diseases

INTRODUÇÃO: A doença renal crônica consiste na perda lenta, progressiva e irreversível da função renal. É considerada um problema social e economico, pois está relacionada a inúmeras doenças associadas, bem como a altos gastos em saúde pública. Sabe-se que os pacientes dialíticos passam por longos períodos de restrição da atividade física repercutindo em disfungoes nos mais diversos sistemas e na qualidade de vida (QV). OBJETIVO: Verificar os efeitos de uma intervenção fisioterapêutica nos pacientes em hemodiálise para: função da musculatura respiratória, força de preensão manual e QV. METODOLOGIA: Estudo experimental, não randomizado, quantitativo e qualitativo; amostra de 13 pacientes, 43,69 ± 9,28 anos, submetidos à hemodiálise na Santa Casa de Diamantina/MG, selecionados por conveniência. Todos realizaram avaliação das pressões respiratórias máximas (PImáx e PEmáx) e do pico de fluxo expiratório (PFE), antes e após a fisioterapia que consistiu de três sessões semanais, durante 2 meses de: exercícios para membros superiores, com técnica de FNP e respiração diafragmática; exercícios de fortalecimento para membros inferiores e exercícios com bola exercitadora para preensão manual. O tratamento estatístico foi realizado através do teste t de Student com valor de significância em p < 0,05. RESULTADOS: As médias respectivamente das variáveis pré- e pós-intervenção foram PI , (97,69 ± 28,3 cmH2O e 98,46 ± 23,399ªdriH2O) p = 0,93; PEmáx (83,07 ± 31,19 cmH2O e 88,46 ± 14,05 cmH2O) p = 0,46 e PFE (375,38 ± 75,23 L/min e 416,15 ± 57,37 L/min) p = 0,02. A media do dinamometro pré-intervenção: 57,23 ± 17,39 kgf e pósintervenção: 56,61 ± 16,09 kgf. No SF-36, que avalia QV, observou-se melhora dos oito domínios, exceto do item 'vitalidade'. De todas as variáveis mensuradas, somente o PFE mostrou-se estatisticamente significante. CONCLUSÃO: O protocolo fisioterapêutico proposto não promoveu melhoras expressivas, do ponto de vista estatístico, nas variáveis analisadas em pacientes submetidos à hemodiálise, justificando-se em parte ao número pequeno da amostra, tempo do protocolo e intervenções propostas.

INTRODUCTION: Chronic kidney disease consists in the slow, progressive and irreversible loss in renal function and it is considered a social and economic problem worldwide, since it is linked to numerous diseases, as well as to higher public health spending. It is known that dialysis patients undergo a long period of restricted physical activity reflects in dysfunctions in various organical systems and in the quality of their lives. OBJECTIVE: To verify the results of physical therapy intervention in patients on hemodialysis, for respiratory muscle function, grip strength and quality of life. METHODOLOGY: Experimental, nonrandomized, quantitative and qualitative of a sample of 13 patients, 43.69 ± 9.28 years, on hemodialysis in the hospital Santa Casa de Diamantina/MG, selected by convenience. All patients were evaluated for maximal respiratory pressures (PImax e PEmax ) and peak expiratory flow (PFE), before and after physiotherapy, which consisted of 3 sessions per week for a period of 2 months weeks: exercises for upper limbs, with technique PNF and breathing diaphragmatic; strengthening exercises for lower limbs and use of exerciser ball. Statistical analysis was performed using the student-t test and significance value at p < 0.05. RESULTS: Respective means for the variables before and after intervention were: PImáx (97.69 ± 28.3 cmH2O e 98.46 ± 23.39 cmH2O) p = 0.93; PEmáx (83.07 ± 31.19 cmH2O e 88.46 ± 14.0 cmH2O) p = 0.46 e PF (375.38 ± 75.23 L/min e 416.15 ± 57.37 L/min) p = 0.02. The dynamometer average pre intervention was: 57.23 ± 17.39 kgf and post intervention: 56.61 ± 16.09 kgf. In the SF-36, which evaluates the quality of life, improvement was observed in the eight domains, except the item 'vitality'. Of all the variables measured only the PFE was statistically significant. CONCLUSION: The proposed physical therapy protocol did not promote significant improvements in those variables, the statistical point, explaining in part the small sample size, time of protocol and proposed interventions.

El eje cardiorrenal: una nueva estrategía con trascendencia clínica / Cardiorenal axis: a new strategy with transcendence clinic

La encrucijada entre corazón y riñón ha llevado a los investigadores a considerar nuevos abordajes en ambas patologías. La microalbuminuria es reflejo del daño endotelial y de la agresión vascular a nivel del glomérulo y está asociada con todos los factores vasculares de riesgo que se relacionan con el daño vascular y la tasa de filtración glomerular, la cual hoy día ha demostrado una estrecha relación con la evolución de los pacientes con enfermedad cardíaca o hipertensión arterial (HTA). Estas dos mediciones reflejan diferentes aspectos del riesgo cardiorrenal. Los principales factores de riesgo cardiovascular, tales como la HTA, tabaquismo, diabetes mellitus y dislipidemia, comúnmente se encuentran asociados con la enfermedad renal crónica (ERC), pero confrecuencia son ignorados o no bien tratados. La enfermedad renal es un problema de salud pública en crecimiento en la mayoría de los países y el número de personas portadoras de ERC se ha incrementado sustancialmente en los últimos 20 años. Este incremento ha ocurrido, principalmente, en las personas mayores de 65 años de edad, en los hipertensos y en los diabéticos. Proponemos el eje cardiorrenal como un concepto integrado con visión novedosa enfocada en el control de los factores mayores de riesgo cardiovascular y en la vigilancia de la función renal.

The relationships between cardiac and renal diseases have led investigators to consider new approaches to both pathologies. Microalbuminuria is a reflection of endothelial and vascular injury at the level of the glomeruli and is associated with all the vascular risk factors that relate to vessel damage and the glomerular filtration rate, which has been demonstrated to bear a close relationship with progression of cardiac disease or arterial hypertension in patients. Thus these two assessments reflect different aspects of cardiorenal risk. Major cardiovascular risk factors such as hypertension, smoking, diabetes mellitus and dyslipidemia are commonly associated with chronic renal disease but frequently ignored or not well treated. Kidney disease is a growing public health problemin most countries and the number of persons with treated end-stagerenal disease (ESRD) has increased substantially during the past 20 years. This increase has occurred primarily in individuals older than 65 year of age, in hypertensive and indiabetic patients. We propose a cardiorenal axis as an integrated concept with a novel vision focused on the control of major cardiovascular risk factors and monitoring of renal function.

Monitoring renal function: measured and estimated glomerular filtration rates: a review

Chronic kidney disease (CKD) is a wrld-wide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. This finding has led to the hypothesis that earlier recognition of kidney disease and successful intervention may improve outcome. The National Kidney Foundation, through its Kidney Disease Outcomes Quality Initiative (K/DOQI), and other National institutions recommend glomerular filtration rate (GFR) for the definition, classification, screening, and monitoring of CKD. Blood creatinine clearance, the most widely used clinical marker of kidney function, is now recognized as an unreliable measure of GFR because serum creatinine is affected by age, weight, muscle mass, race, various medications, and extra-glomerular elimination. Cystatin C concentration is a new and promising marker for kidney dysfunction in both native and transplanted kidneys. Because of its low molecular weight, cystatin C is freely filtered at the glomerulus and is almost completely reabsorbed and catabolized, but not secreted, by tubular cells. Given these characteristics, cystatin C concentration may be superior to creatinine concentration in detecting chronic kidney disease. This review aims to evaluate from recent literature the clinical efficiency and relevance of these GFR markers in terms of screening CKD.

Aging and the periodontium: [review]

The geriatric population has been growing fast over the last decades in Brazil and all over the world, changing demographics. Additionally, increased knowledge and the advances of modern dentistry have led the old population to retain more natural teeth, needing specialized dental services for a longer time. Changes in biochemical and physiological processes occur with aging in all body tissues, including the periodontium. The association between periodontal and systemic diseases has also been widely discussed, suggesting the need of a multidisciplinary care, especially in older adults, who are frequently affected by chronic systemic conditions and multiple drug therapy. These features lead to a highly complex management of the geriatric population, challenging the dental care providers. The aim of this study is to review the age-related changes and the consequences of other factors, such as systemic diseases and drugs, on the periodontium of aged patients.

Efeito de uma sessão de hemodiálise sobre o estresse oxidativo sistêmico de pacientes renais crônicos terminais / Effect of a hemodialysis session on oxidative stress of chronic kidney disease patients

Objetivo: Avaliar a repercussão de uma sessão de hemodiálise (HD) sobre o estresse oxidativo sistêmico de pacientes renais crônicos. Métodos e resultados: Foram avaliados 17 pacientes (10 mulheres) com média de idade de 39,9+- 13,5 anos em tratamento hemodialítico na Unidade de Nefrologia do HCPA, e o grupo controle formado por 18 indivíduos saudáveis (4 mulheres), com média de idade de 34.8 +- 10,1 anos. o sangue dos doentes renais foi coletado antes e após a sessão de HD. As médias foram analisadas pelo teste t de Student (p<0,05). Nos eritrócitos, avaliou-se a atividade das enzimas antioxidantes superóxido dismutase (SOD) e catalse (CAT). No plasma, avaliou-se o sistema antioxidante não enzimático por meio da mensuração da capacidade antioxidante total (TRAP). Não houve diferença significativa entre os valores de SOD e CAT antes e após HD. Comparando com o grupo controle, observou-se redução significativa na atividade dessas enzimas. O TRAP apresentou redução significativa após sessão de HD. O dano oxidativo a lipídios de membrana foi avaliado por quimiluminescência (QL), enquanto o dano às proteínas, pelo método das carbonilas. Não houve diferença significativa entre os valores de QL e Carbonilas após HD. Porém, quando comparados com o grupo controle, observou-se diferença significativa indicando maior dano aos lipídios de membrana e às proteínas nos doentes renais. Conclusões: pacientes renais crônicos tratados com HD apresentam redução na atividade das enzimas antioxidantes SOD e CAT, bem como dano oxidativo aumentado quando comparado com indivíduos saudáveis e uma sessão de HD não modifica esses níveis.

Objective: To evaluate the effect of a session of hemodialysis (HD) on systemic oxidative stress in chronic renal patients. Methods: We evaluated 17 patients (10 women) with mean age of 39.9 + - 13.5 years on hemodialysis in the Nephrology Unit of HCPA, and the control group of 18 healthy subjects (four women) with mean age of 34.8 + - 10.1 years. the blood of kidney patients was collected before and after HD session. Means were analyzed by Student t test (p <0.05). In erythrocytes, we evaluated the activity of antioxidant enzymes superoxide dismutase (SOD) and catalse (CAT). In plasma, we assessed the non-enzymatic antioxidant system by measuring the total antioxidant capacity (TRAP). There was no significant difference between the values of SOD and CAT before and after HD. Compared with the control group showed a significant reduction in the activity of these enzymes. The TRAP decreased significantly after HD session. Oxidative damage to membrane lipids was assessed by chemiluminescence (CL), while damage to proteins by the method of the carbonyls. There was no significant difference between the values of QL and carbonyls after HD. However, when compared with the control group, there was a significant difference, indicating greater damage to membrane lipids and proteins in kidney patients. Conclusions: chronic renal failure patients treated with HD show a reduction in activity of antioxidant enzymes SOD and CAT, as well as increased oxidative damage compared with healthy subjects and one HD session does not modify these levels.

Acción novedosa de la aldosterona en la nefrotoxicidad por ciclosporina / Novel action of aldosterone in CsA nephrotoxicity

Calcineurin inhibitors are helpful ímmunosuppressíve agents in clinical practice. Thanks to their lower cost respect with new ímmunosuppressíve therapy, calcineurin inhibitors in our country continue being the most used treatment in solid organ transplant recipients or patients with autoimmune disease. In the 80's decade cyclosporine A (CsA) was introduced as the first calcineurin inhibitor transforming the immunosuppression therapy. Up to date, many articles evaluating beneficial and adverse effects of CsA have been published. In this review, basic aspects and actions of CsA are analyzed together with studies from our laboratory that pointed out the pathophysiological role of aldosterone as a mediator of functional and structural changes that are observed in CsA nephrotoxicity. Based in our findings, we proposed that in CsA nephrotoxicity, the aldosterone mediates renal vasoconstriction and enhances TGFJ3 expression promoting the development of nefrotoxicity. Finally, results from our laboratory and others allow us to suggest that aldosterone receptors blockade with spironolactone or eplerone could be a pharmacological therapy to reduce or prevent acute and chronic CsA nephrotoxicity in transplant recipients.

Los inhibidores de calcineurina son los agentes inmunosupresores más potentes con los que se cuenta en la práctica clínica, y gracias a su bajo costo respecto a las nuevas terapias inmunosupresoras, en nuestro país continúan siendo los agentes terapéuticos más utilizados para el manejo de pacientes con enfermedades autoinmunes o que reciben trasplantes. En la década de los 80's se introdujo la ciclosporina A (CsA) como primer inhibidor de calcineurina, lo cual revolucionó la terapia inmunosupresora. Desde entonces se han publicado muy variados artículos donde se han evaluado los efectos benéficos y deletéreos de estos inhibidores; específicamente nos enfocaremos a revisar las acciones de CsA y, en particular, los resultados de nuestro laboratorio que muestran el papel fisiopatológico que juega la aldosterona como mediador de los cambios funcionales y estructurales que se observan en la nefrotoxicidad por ciclosporina. Específicamente su participación en promover la vasoconstricción renal asociada a CsA y en el desarrollo de fibrosis al inducir la expresión de TGFβ. Por lo tanto, nuestros resultados y los de otros autores nos permiten proponer el bloqueo de los receptores de aldosterona con espironolactona o eplerone como un tratamiento farmacológico útil para reducir la incidencia de nefrotoxicidad aguda y crónica, inducida por CsA en pacientes con enfermedades autoinmunes o que reciben trasplante de órganos.

Estudo do sistema renina-angiotensina intrarenal em modelo experimental de nefropatia crônica progressiva / A study of the intrarenal renin-angiotensin system in a experimental model of progressive chronic nephropathy

A Ang II é um agente fibrogênico que contribui para a progressão de doenças renais crônicas que possivelmente é produzida localmente no rim. Foram estudados ratos com doença renal por depleção de óxido nítrico. Os principais achados foram: 1) os animais doentes, com hipertensão, albuminúria e lesão renal histológica têm renina e Ang II plasmáticas normais; 2) o rim apresenta toda a maquinaria necessária à produção local de Ang II; 3) há aumento da expressão de Ang II e de seu receptor AT1 no interstício renal de animais doentes; 4) a regulação da Ang II local é diferente da sistêmica, uma vez que o losartan diminui a Ang II local e aumenta a sistêmica; 5) a catepsina D pode contribuir para a geração local de Ang II; e 6) Os fibroblastos podem participar da geração local de Ang II e esta produção pode ser influenciada por TNF-a e IL-1b.Ang II is an well known fibrogenic agent that contributes to the progression of chronic renal disease and seems to be locally produced inside the kidney. Rats with renal disease caused by nitric oxide depletion were studied. The main results are: 1) the rats were hypertensive, albuminuric and with histologic renal damage but had normal plasma renin and Ang II; 2) the kidney has a complete machinery to produce Ang II; 3) Ang II and AT1 receptor were highly expressed in injured kidneys; 4) the regulation of local Ang II production differs from the systemic one, since losartan diminishes local while increases systemic Ang II; 5) cathepsin D may contribute to local Ang II generation; and 6) fibroblasts may produce Ang II locally under the stimuli of TNF-a and IL-1b...

Nefropatía tubular por carencia prolongada de potasio / Tubular nephropathy from chronic potassium deficiency

Fueron estudiados 2 casos con desnutrición crónica avanzada e hipokalemia acentuada en los cuales se encontraron disminución de la filtración glomerular y del flujo renal plasmático, presencia de poliuria con hiposmolaridad sérica e hipotonía urinaria, las cuales no se modificaron durante la administración de hormona antidiurética. Uno de dichos casos tuvo una evolución fatal, a pesar de la administración de suplemento de potasio por vía oral, y el estudio histopatológico de sus riñones demostró la conservación de los glomérulos y la presencia de degeneración vacuolar hidrópica en el epitelio de los túbulos proximales. El otro caso evolucionó favorablemente hacia la recuperación y un nuevo estudio practicado al mes de su ingreso demostró la normalización de sus alteraciones fisiopatológicas. Tanto las alteraciones anatómicas, como las funcionales se han descrito en diversas condiciones patológicas que tienen en común la pérdida crónica de potasio por diferentes vías. Se ha observado la reversibilidad de estas lesiones pero igualmente existe la posibilidad de una falta de respuesta a la administración de potasio y la evolución hacia la insuficiencia renal y a la muerte. El curso del trastorno puede estar condicionado por la intensidad y la duración de la depleción de potasio. Los estudios experimentales en que se ha impedido la aparición de estas lesiones en ratas deplecionadas de potasio que recibían rubidio y cesio, así como la desaparición de las lesiones ya presentadas con la administración de estos elementos, han sugerido que no sea propiamente la deficiencia de potasio la responsable directa de esta neforpatía, sino

Trasplante renal en niños: experiencia inicial / Pediatric renal transplantation: initial experience

Se revisaron los expedientes clínicos de todos los niños con transplantes de riñon en el Hospital de Ginecopediatría, Centro Médico Nacioanl en León, Guanajuato, a partir del inicio del programa de transplante. Entre junio de 1989 y marzo de 1993 se han realizado trasplantes a 19 niños, trece hombres y seis mujeres. Las edades han variado entre cinco y 16 años. La etiología de enfermedad renal terminal identificada con mayor frecuencia fue glomerulonefritis crónica. Al momento del transplante 17 pacientes se encontraban en programas de diálisis peritoneal y dos en hemodiálisis. En 13 niños el órgano se obtuvo de donador vivo y en seis de cadáver. Después de un seguimiento de tres a 44 meses con media de 19, la tasa de sobrevida de pacientes es de 84.2 por ciento, y la de órganos de 63.2 por ciento. El trasplante es una alternativa de tratamiento que requiere de la integración de un equipo multidisciplinario con experiencia en la atención del paciente en edad pediátrica. Los resultados iniciales en este hospital parecen alentadores

Compromiso renal en el mieloma múltiple / Renal compromise in the multiple myeloma

Se efectúa una revisión de los aspectos básicos de la fisiopatología y de la clínica del mieloma múltiple. Se exponen los mecanismos de daño renal de esta enfermedad, asi como su expresión anatomopatológica y clínica. Se revisa la terapéutica de esta nefropatía, incluyendo una enumeración de las medidas preventivas y una exposición de los tratamientos de la insuficiencia renal tanto aguda como crónica. Se exponen los principales aspectos de la nefropatía por cadenas livianas