Evaluation of oxidant-antioxidant balance in patients on maintenance haemodialysis: a comparative study of dialyzers membranes.

BACKGROUND: Haemodialysis (HD) exacerbates oxidative stress (OS). The polymethyl-methacrylate (PMMA)-BK-F membrane ameliorates OS and inflammation markers compared to polyacrylonitrile (PAN/AN69) and cellulose membranes. This may be due to the size of pore radius, high flux or other specific properties of PMMA membranes. AIM: To compare OS and inflammatory status in HD-treated end stage renal disease patients with membranes of different pore size radius and flux. METHODS: 47 patients of both sexes were studied. The HD membranes with which the patients were normally treated were changed to BK-P or B-3 membranes for 6 months. Intracellular and extracellular components of the oxidant-antioxidant balance (OAB), C-reactive protein (CRP), beta2-micro-globulin (beta2mu-globulin), albumin and transferrin were measured. RESULTS: A significant decrease in red cell membrane thiobarbituric acid reacting substances and an increase in cytosolic superoxide dismutase (SOD) and plasma total antioxidant substances were observed in all patients after 6 months of treatment with BK-P and B-3 membranes except SOD and CRP in patients previously dialysed with triacetate cellulose membranes. Albumin and transferrin remained unmodified. beta2mu-globulin significantly decreased after treatment with PMMA membranes. CONCLUSION: BK-P and B-3 HD membranes improved the OAB, beta2mu-globulin and CRP compared to PAN/AN69 and cellulose diacetate membranes.

[Pharmacogenetics of angiotensin system in non diabetic nephropathy]. / Farmacogenética del sistema de la angiotensina en la nefropatía no diabética.

BACKGROUND: Genetic variability could contribute to the response to pharmacological treatment in patients with nephropathy. In albuminuric diabetic patients the renoprotective effect of angiotensin I-converting enzyme (ACE) inhibition should be lower among homozygotes for the deletion allele (DD) compared to II-homozygotes. METHODS: A total of 71 non-diabetic chronic nephropathy patients were treated with losartan (n = 37) or amlodipine (n = 34). Blood pressure and proteinuria were determined before and after the treatment, and changes in the mean values were statistically compared. Patients were genotyped for the ACE-I/D, angiotensin I receptor type 1 (AGTR1)-1166 A/C, and angiotensinogen (AGT)-M235T polymorphims, and the reduction of blood pressure and proteinuria between the different genotypes were compared. RESULTS: The reduction in systolic or diastolic blood pressure was not found to be different between the ACE-I/D or AGT-M/T genotypes in patients treated with losartan or amlodipine. In patients treated with losartan, we found a significantly higher reduction of diastolic blood pressure in AGTR1-AA patients compared to AC patients (p = 0,0024). We did not find differences in proteinuria-reduction between the different genotypes in patients treated with losartan or amlodipine. CONCLUSIONS: Our data show that the effects of losartan and amlodipine on the absolute mean reduction of blood pressure and proteinuria in non-diabetic nephropathy patients are similar between the different ACE or AGT genotypes. Although based on a small number of patients, the AGTR1-AA genotype was associated with a significantly higher reduction in diastolic blood pressure among losartan-treated patients. Additional studies are necessary to refute or confirm this association.

Farmacogenética del sistema de la angiotensina en la nefropatía no diabética / Pharmacogenetics of angiotensin system in non diabetic nephropathy

Antecedentes: La variación genética podría contribuir a la respuesta farmacológica en los pacientes con nefropatía. Así, entre los pacientes con albuminuria diabética aquellos con el genotipo DD para el gen de la enzima convertidora de la angiotensina (ECA, polimorfismo inserción/delección, I/D) tendrían una menor respuesta renoprotectora ante los inhibidores de la ECA, comparados con los pacientes con genotipo II. Métodos: Estudiamos 71 pacientes con nefropatía crónica no diabética, de los cuales 37 habían sido tratados con losartán y 34 con amlodipino. Determinamos la tensión arterial y la proteinuria antes y después de ser tratados, y los valores medios se compararon estadísticamente. Todos los pacientes fueron genotipados para los polimorfismos I/D de la ECA, 1166 A/C del receptor de tipo 1 de la angiotensina I (AGTR1), y M235T del angiotensinógeno (AGT), y los valores medios de la reducción de la tensión sanguínea y la proteinuria fueron comparados entre los genotipos. Resultados: No hallamos diferencias en la reducción de la presión sanguínea diastólica o sistólica entre los diferentes genotipos de los polimorfismos de la ECA y el AGT, tanto para los pacientes tratados con losartán como con amlodipino. En los pacientes tratados con losartán hubo una reducción significativa de la presión diastólica entre aquellos con genotipo AGTR1-AA comparados con los heterocigotos AC (p = 0,0024). No hallamos diferencias en el nivel de reducción de la proteinuria entre los diferentes genotipos, tanto entre los tratados con losartán como con amlodipino. Conclusiones: De acuerdo con nuestros resultados, los valores medios de reducción de la presión sanguínea en los pacientes con nefropatía no diabética y tratados con losartán o amlodipino serían similares entre los diferentes genotipos de la ECA y el AGT. Aunque nuestro estudio se basó en un número reducido de pacientes, el genotipo AGTR1-AA podría estar asociado con una mayor reducción de la presión diastólica entre los pacientes tratados con losartán

Background: Genetic variability could contribute to the response to pharmacological treatment in patients with nephropathy. In albuminuric diabetic patients the renoprotective effect of angiotensin I-converting enzyme (ACE) inhibition should be lower among homozygotes for the deletion allele (DD) compared to II-homozygotes. Methods: A total of 71 non-diabetic chronic nephropathy patients were treated with losartan (n = 37) or amlodipine (n = 34). Blood pressure and proteinuria were determined before and after the treatment, and changes in the mean values were statistically compared. Patients were genotyped for the ACE-I/D, angiotensin I receptor type 1 (AGTR1)-1166 A/C, and angiotensinogen (AGT)-M235T polymorphims, and the reduction of blood pressure and proteinuria between the different genotypes were compared. Results: The reduction in systolic or diastolic blood pressure was not found to be different between the ACE-I/D or AGT-M/T genotypes in patients treated with losartan or amlodipine. In patients treated with losartan, we found a signiticantly higher reduction of diastolic blood pressure in AGTR1-AA patients compared to AC patients (p = 0,0024). We did not find differences in proteinuria-reduction between the different genotypes in patients treated with losartan or amlodipine. Conclusions: Our data show that the effects of losartan and amlodipine on the absolute mean reduction of blood pressure and proteinuria in non-diabetic nephropathy patients are similar between the different ACE or AGT genotypes. Although based on a small number of patients, the AGTR1-AA genotype was associated with a significantly higher reduction in diastolic blood pressure among losartan-treated patients. Additional studies are necessary to refute or confirm this association

[Renal markers and predictors, and renal and cardiovascular risk factors]. / Marcadores y predictores renales y factores de riesgo renal y cardiovascular.

An important task of the nephrologists during the last century, it has been the search of elements and means that allow us, with the adequate precision, to correlate the functional deterioration of the kidney, and the patient's clinical reality. And the continuous searching of factors and markers that injure them, the prognosis, and early diagnosis, to be able to predict the degree of the organs and patient's survival. Almost parallel survival presage in the natural history of the illness, almost one century ago. In the second half of the XX century, in the developed countries, appear modifications of the social, cultural, and sanitary conditions, that make appear some very different partner-sanitary and epidemic circumstances, and take place like they are, among others: 1. An increase of per cápita private rents, what takes place to increase of the level of social life and the population's health. With increment of the longevity, and smaller incidence and prevalence of classic process, as malnutrition, infections, infantile mortality, so increasing the weight of the cardiovascular diseases and death. This is potentiated for the increment and the incidence of environmental cardiovascular risk's factors (like high caloric and fatty-rich diets, smoke, alcohol, disappearance of the physical work, inactivity, etc). And that situations are also product of the change of the outline of human and social values and guides. 2. Access of the whole population to a sanitary attention of more quality and effectiveness. It allows the biggest survival of patients that suffer vascular crisis, (as angina, miocardial infarction or cerebrovascular accident), that few years ago they have had a higher morbimortality and an inferior survival (2). 3. The execution of big epidemic studies has been able to, not only characterize and test with scientific evidence to numerous factors and markers, that induce renal and cardiovascular prejudicial changes, but risk and death probability prediction. And also, its possible association nexuses, its injuring mechanisms, and the characterization of the new "emergent" renal and cardiovascular risk's markers and factors. 4. The impact on the possibility to treat the end stage renal disease with effective and prolonged procedures, by hemodialisis or kidney transplantation, has been occurred. The affected population's survival with the adequacy renal-sustitution treatment, and the possibility of indefinite duration of its treatment, has also impacted on the public health, and its resources, in an evident way. Simultaneously to increase of the incidence in the population, the electivity for the treatment has been enlarged and extended increasing it exponentially. These facts are documented here, and are defined the characteristics of the factors and markers of risk, of renal and cardiovascular diseases. The defined factors are valued to mark, so far as with the well-known evidence is possible, the prediction and the progression of the renal and cardiovascular functional deterioration: The hypertension, cardiovascular remodeling, the arterial stiffness, the heart rate, the sympathetic activation, the modification of the physiological response of the target organ to the overcharge, the metabolic syndrome, the obesity, the insulin resistance, the altered lipid profile, and metabolism of the fatty acids, the salt-sensibility, the decrease of the renal functional reserve, the glomerular hyperfiltration, the absence of the arterial pressure nocturnal descent, the abnormal excretion of proteins for the urine, the phenomenon induced by dysfunctions of the clotting, superoxide production, growth factors, the production of chronic inflammation and its markers, the factors of the glomerulosclerosis progression, the hyperuricemic status, the endothelial dysfunction and others, are evaluated. As well as their association among them and with other factors of risk not changeable like the age, and in turn, with other acquired voluntarily factors of risk, as the smoking habit and the alcohol. These facts are now impacting on the population's sanity. And also in the professional nephrologic exercise, so much for the cardiovascular and renal morbimortality increased, as for the increase of the incidence of end-stage renal disease susceptible to treat with of substitutive procedures. They try to justify the sentence of Alan Weder of the heading, and other concepts like "epidemic factors of the XXI century", and intuitive expressions like "predialitic endothelial disruption or ruin".

Marcadores y predictores renales y factores de riesgo renal y cardiovascular / Markers, renal predictors, and factors, of renal and cardiovascular risk factors

Una parte importante del afán de los nefrólogos desde el siglo pasado, ha sido la búsqueda de elementos y medios que permitan con la precisión necesaria correlacionar el deterioro funcional renal y la realidad clínica del paciente. Y la búsqueda de factores y marcadores lesionales, diagnósticos y pronósticos, para poder predecir el grado de supervivencia del órgano y del paciente. Pronósticos de supervivencia casi paralelos en el tiempo de la historia natural de la enfermedad, hace casi un siglo. En la segunda mitad del siglo XX, en los «países desarrollados» se producen modificaciones de las condiciones sociales, culturales y sanitarias que hacen aparecer unas circunstancias socio-sanitarias y epidemiológicas muy diferentes, como son entre otras: 1. Aumento de renta per cápita, lo que lleva a aumento del nivel de vida social y sanitario de la población. Con incremento de la longevidad, y menor incidencia y prevalencia de procesos «clásicos», como desnutrición, infecciones, mortalidad infantil, aumenta el peso de la enfermedad y muerte cardiovascular. Hecho potenciado por el incremento de la incidencia de factores de riesgo cardiovascular medioambientales (dietas grasas hipercalóricas, tabaquismo, alcohol, desaparición del trabajo físico, inactividad, etc.), que son también producto del cambio del esquema de valores sociales e individuales. 2. Acceso de toda la población a una atención sanitaria de mayor calidad y eficacia, que permite la mayor supervivencia de pacientes que sufren crisis agudas vasculares (como el infarto agudo de miocardio o ictus apoplético), y que hace pocos años tenían una morbi-mortalidad muy superior y una supervivencia inferior. 3. La ejecución de grandes estudios epidemiológicos han conseguido caracterizar con pruebas de evidencia no sólo a numerosos factores y marcadores que inducen cambios lesivos renales y cardiovasculares, y de predicción de muerte, sino también sus posibles nexos de asociación, sus mecanismos lesionales, y la caracterización de los mismos. 4. El impacto que ha producido la posibilidad de tratamiento sustitutivo, eficaz, sobre la supervivencia de la población con insuficiencia renal terminal, y la posibilidad de duración indefinida de su tratamiento, ha impactado también sobre la salud pública, y sus recursos, de forma evidente. Simultáneamente a un aumento de la incidencia en la población de la insuficiencia renal crónica, las indicaciones del tratamiento se han ampliado y extendido incrementándola exponencialmente. Se documentan estos hechos, se definen las características de los factores y marcadores de riesgo, y se valoran los factores definidos, que marcan con la evidencia conocida hasta la fecha, la predicción de la progresión del deterioro funcional renal y cardiovascular: La hipertensión arterial, el remodelado cardiovascular y la rigidez arterial, la frecuencia cardíaca, la activación simpática, la modificación de respuestas a las sobrecargas, el síndrome metabólico, la obesidad, la resistencia a la insulina, la dislipemia, el metabolismo alterado de los ácidos grasos, la sal-sensibiliad, la disminución de la reserva funcional renal, la hiperfiltración glomerular, la ausencia del descenso nocturno de la presión arterial, la excreción anormal de proteínas por la orina, la insuficiencia renal, los fenómenos inducidos por trastornos de la coagulación, la producción de superóxidos, de factores de crecimiento, de marcadores de inflamación crónica, los factores de la progresión de la glomérulosclerosis, la hiperuricemia, la disfunción endotelial,y otros, son valorados. Así como su asociación entre ellos y con otros factores de riesgo no modificables como la edad, y a su vez, con otros factores de riesgo adquiridos como el tabaquismo y el alcohol. Todo ello para valorar asimismo la trascendencia que tienen estos hechos que inciden en la sanidad de la población, y en el ejercicio profesional del nefrólogo, tanto por la morbi-mortalidad cardiovascular incrementada como por el aumento de la incidencia de insuficiencia renal susceptible de tratamientos sustitutivos. Se intentan justificar documentalmente desde la frase de Alan Weder del encabezamiento hasta conceptos como «epidemias del siglo XXI», y expresiones intuitivas como «ruina endotelial prediálisis» (AU)

An important task of the nephrologists during the last century, it has been the search of elements and means that allow us , with the adequate precision, to correlate the functional deterioration of the kidney, and the patient’s clinical reality. And the continuous searching of factors and markers that injure them, the prognosis, and early diagnosis, to be able to predict the degree of the organs and patient’s survival. Almost parallel survival presage in the natural history of the illness, almost one century ago. In the second half of the XX century, in the developed countries, appear modifications of the social, cultural, and sanitary conditions, that make appear some very different partner-sanitary and epidemic circumstances, and take place like they are, among others: 1. An increase of per cápita private rents, what takes place to increase of the level of social life and the population’s health. With increment of the longevity, and smaller incidence and prevalence of classic process, as malnutrition, infections, infantile mortality, so increasing the weight of the cardiovascular diseases and death. This is potentiated for the increment and the incidence of environmental cardiovascular risk’s factors (like high caloric and fatty-rich diets, smoke, alcohol, disappearance of the physical work, inactivity, etc). And that situations are also product of the change of the outline of human and social values and guides. 2. Access of the whole population to a sanitary attention of more quality and effectiveness. It allows the biggest survival of patients that suffer vascular crisis, (as angina, miocardial infarction or cerebrovascular accident), that few years ago they have had a higher morbimortality and an inferior survival (2). 3. The execution of big epidemic studies has been able to, not only characterize and test with scientific evidence to numerous factors and markers, that induce renal and cardiovascular prejudicial changes, but risk and death probability prediction.And also, its possible association nexuses, its injuring mechanisms , and the characterization of the new «emergent» renal and cardiovascular risk’s markers and factors. 4. The impact on the possibility to treat the end stage renal disease with effective and prolonged procedures, by hemodialisis or kidney transplantation, has been occured. The affected population’s survival with the adequacy renal-sustitution treatment, and the possibility of indefinite duration of its treatment, has also impacted on the public health, and its resources, in an evident way. Simultaneouslyto increase of the incidence in the population , the electivity for the treatment has been enlarged and extended increasing it exponentially. These facts are documented here, and are defined the characteristics of the factors and markers of risk, of renal and cardiovascular diseases. The defined factors are valued to mark, so far as with the well-known evidence is possible, the prediction and the progression of the renal and cardiovascular functional deterioration. The hypertension, cardiovascular remodeling, the arterial stiffness, the heart rate, the sympathetic activation, the modification of the physiological response of the target organ to the overcharge, the metabolic syndrome, the obesity, the insulin resistance, the altered lipid profile, and metabolism of the fatty acids, the salt-sensibility, the decrease of the renal functional reserve, the glomerular hyperfiltration, the absence of the arterial pressure nocturnal descent, the abnormal excretion of proteins for the urine, the phenomenon induced by dysfunctions of the clotting, superoxide production, growth factors, the production of chronic inflammation and its markers, the factors of the glomerulosclerosis progression, the hiperuricemic status, the endothelial dysfunction and others, are evaluated. As well as their association among them and with other factors of risk not changeable like the age, and in turn, with other acquired voluntearely factors of risk, as the smoking habit and the alcohol. These facts are now impacting on the population’s sanity. And also in the professional nephrologyc exercise, so much for the cardiovascular and renal morbimortality increased, as for the increase of the incidence of end-stage renal disease susceptible to treat with of substitutive procedures. They try to justify the sentence of Alan Weder of the heading, and other concepts like «epidemic factors of the XXI century», and intuitive expressions like «predialitic endothelial disruption or ruin» (AU)

Comparison of losartan and amlodipine in renally impaired hypertensive patients.

Effects of losartan and amlodipine on blood pressure and albuminuria were compared in a randomized, double-blind, parallel trial involving 48 patients with essential hypertension (sitting diastolic blood pressure between 95 to 115 mm Hg) and impaired renal function (creatinine clearance of 30 to 60 ml/min/1.73 m2). After four weeks of placebo administration, patients were stratified according to baseline albuminuria (< or > or = 300 micrograms/min) and randomized to once-daily treatment with losartan 50 mg (N = 24) or amlodipine 5 mg (N = 24) for 12 weeks. Titration to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg or amlodipine 10 mg was possible at weeks 3 or 6 for patients having an inadequate blood pressure response. After 12 weeks of treatment, the mean decreases in sitting diastolic and systolic blood pressures were significantly larger in the losartan group (-18.1 +/- 7.2 and -27.7 +/- 15.2 mm Hg) than in the amlodipine group (-12.4 +/- 7.5 and -16.3 +/- 12.1 mm Hg; P = 0.009 and P = 0.008, respectively). The greater antihypertensive response to losartan was not influenced by the initial degree of albuminuria. The losartan and amlodipine regimens were well-tolerated. Baseline levels of albuminuria were reduced after 12 weeks of losartan treatment (median change of -29.5 micrograms/min), while amlodipine therapy was associated with a median increase (48.4 micrograms/min) in this renal marker at week 12. The treatment difference was statistically significant (P = 0.021). These results indicate that losartan 50 mg, administered alone or in combination with HCTZ 12.5 mg, is more effective than amlodipine 5/10 mg in lowering blood pressure and albuminuria in patients with essential hypertension complicated by impaired renal function.