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1.
Nat Genet ; 24(3): 251-6, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10700177

RESUMEN

Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion. Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition. FSGS is characterized by increased urinary protein excretion and decreasing kidney function. Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref. 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS. In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4. Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients. Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage.


Asunto(s)
Actinina/fisiología , Cromosomas Humanos Par 19/genética , Glomeruloesclerosis Focal y Segmentaria/genética , Proteínas de Microfilamentos , Actinina/deficiencia , Actinina/genética , Actinas/metabolismo , Secuencia de Aminoácidos , Citoesqueleto/metabolismo , Citoesqueleto/ultraestructura , Análisis Mutacional de ADN , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Predisposición Genética a la Enfermedad , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/genética , Masculino , Datos de Secuencia Molecular , Mutación , Linaje , Alineación de Secuencia , Homología de Secuencia de Aminoácido
2.
Clin Nephrol ; 75(4): 328-35, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21426887

RESUMEN

BACKGROUND: Hereditary hemochromatosis is an autosomal recessive condition causing excessive intestinal iron absorption related to C282Y hemochromatosis mutation gene. Dialysis patients receive intravenous iron supplements as treatment for anemia. The gene mutation frequency and its influence on iron deposits and intravenous iron response are unknown in these patients. STUDY DESIGN: Prospective observational. SETTING AND PARTICIPANTS: 290 dialysis patients in Gran Canaria, Spain. OUTCOMES AND MEASUREMENTS: The C282Y hemochromatosis mutation gene was studied. Other active players in iron metabolism have not been included in this study. Red cell parameters, serum iron, transferrin and ferritin concentrations were measured every 2 months for 2 years. RESULTS: No differences in allelic and genotypic frequencies between dialysis patients and the general population were detected. Baseline clinical or analytical parameters were similar in C282Y +/- and C282Y -/- patients. Among those who did not need intravenous iron treatment, C282Y+/- patients maintained constant serum ferritin (302.1 ± 216.7 vs. 319.5 ± 300.5 µg/l after 4 months), whereas C282Y-/- patients showed decreased levels during the same period (306.7 ± 212.2 vs. 221.6 ± 167.8 µg/l, p < 0.001). After 4 months of parenteral iron, serum ferritin increased more intensely in C282Y +/- patients than in C282Y -/- patients (934.2 ± 195.8 vs. 658.7 ± 259.9 µg/l, p < 0.001). A multivariance analysis identified the C282Y allele as the most important factor that explains this difference. CONCLUSIONS: Heterozygosity for the C282Y allele of the hemochromatosis mutation gene could be associated with differences in iron parameters in dialysis patients.


Asunto(s)
Hemocromatosis/genética , Antígenos de Histocompatibilidad Clase I/genética , Hierro/sangre , Proteínas de la Membrana/genética , Mutación Missense , Diálisis Renal , Alelos , Análisis de Varianza , Antígenos de Superficie/genética , Distribución de Chi-Cuadrado , Femenino , Genotipo , Hemocromatosis/sangre , Hemocromatosis/tratamiento farmacológico , Proteína de la Hemocromatosis , Humanos , Hierro/uso terapéutico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estadísticas no Paramétricas
3.
Nefrologia ; 29(4): 327-30, 2009.
Artículo en Español | MEDLINE | ID: mdl-19668304

RESUMEN

BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common life-threatening hereditary disease. Molecular analysis with highly polymorphic short tandem repeats, located in the vicinity of the two genes responsible for the disease (PKD1 and PKD2), is used to confirm diagnosis and give genetic counseling to members of affected families. METHODS: We have developed a new assay to genotype five PKD1 and four PKD2 markers, based on two multiplex PCR reactions, and capillary electrophoresis analysis. A total of 110 subjects, belonging to 14 affected families, were genotyped to confirm the concordance with the singleplex method used previously. RESULTS: The amplicons ranged from 95 to 154 bp in length, and complete STR profiles were obtained from 1-5 ng DNA. The specificity of the multiplex PCR system was 88,5% (95%CI= 75,9-95,2), and the sensitivity, 87,9 (95%CI= 76,1-94,6). CONCLUSIONS: This is a useful strategy that, together with automated computer-based allele detection, allows reliable, simple, faster, and cheaper genetic analysis than the previous singleplex method.


Asunto(s)
Riñón Poliquístico Autosómico Dominante/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Femenino , Humanos , Masculino , Repeticiones de Microsatélite , Riñón Poliquístico Autosómico Dominante/genética , Canales Catiónicos TRPP/análisis , Canales Catiónicos TRPP/genética
4.
Free Radic Res ; 42(1): 82-92, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18324526

RESUMEN

The CYBA gene variants have been inconsistently associated with coronary heart disease (CHD) risk. A case-control study was conducted genotyping 619 subjects to explore the contribution of C242T and A640G to CHD risk in the population. A significant risk was found associated with GG homozygosity (odds ratio (OR) 2.132, 95% confidence interval, 1.113-4.085). The C242T variant was associated with CHD risk in women. Bias due to population stratification was analysed. Phenotype changes linked to these polymorphisms were evaluated. Superoxide measurements revealed higher production as indicated by the presence of the G and T alleles. Differences in mRNA concentration in heterozygous A640G samples were analysed. Higher levels of G allele mRNA compared with A allele mRNA were found. NAD(P)H oxidase p22phox sub-unit expression was evaluated with Western blot. Experiments revealed a gradual relationship in p22phox protein expression according to genotypes of the analysed variants. Those GG TT double homozygous showed increased p22phox protein expressions regarding AA CC double homozygous. This study has demonstrated increased expression and activity of the NAD(P)H system components during atherogenesis and the results could help explain the relevance of the A640G variant as a CHD marker.


Asunto(s)
Enfermedad Coronaria/genética , Regulación Enzimológica de la Expresión Génica , NADPH Oxidasas/genética , Polimorfismo Genético , Adulto , Estudios de Casos y Controles , Células Cultivadas , Enfermedad Coronaria/enzimología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Peróxidos Lipídicos/sangre , Macrófagos/enzimología , Masculino , Arterias Mamarias/enzimología , Persona de Mediana Edad , Monocitos/enzimología , NADPH Oxidasas/metabolismo , Oportunidad Relativa , Fenotipo , Estabilidad del ARN , ARN Mensajero/metabolismo , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , España , Superóxidos/metabolismo , Regulación hacia Arriba
5.
Nefrologia ; 26(5): 559-63, 2006.
Artículo en Español | MEDLINE | ID: mdl-17117898

RESUMEN

BACKGROUND: The nitric oxide synthase (NOS3) G894T gene polymorphism seems as a genetic determinant of total homocysteine (tHcy) concentrations through an effect on folate catabolism. We tested for a significant contribution to blood pressure values for the NOS3 G894T and 4a/b gene polymorphisms and whether those changes could explain the modulating effect on tHcy concentrations. PATIENTS AND METHODS: We analyzed 158 healthy men. The NOS3 gene polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment analysis (G894T) and by PCR (4a/b). Total homocysteine concentrations were evaluated by the fluorescence polarization immunoassay method. RESULTS: In our population we did not obtain a significant contribution of the G894T to blood pressure variations. However, tHcy mean concentration values differed according G894T genotypes (P = 0.01). Interestingly, we did not obtain a significant modulating effect on tHcy concentrations according to 4a/b genotypes although the 4a/b genotype distribution was statistically associated with blood pressure variations. CONCLUSION: Our results showed a modulating effect of the NOS3 4a/b gene variant on tHcy concentrations that is at least partially provoked by discrete blood pressure increments. Nevertheless, our multivariate analysis did not show a statistical significant role for the NOS3 G894T gene polymorphism on tHcy concentrations.


Asunto(s)
Presión Sanguínea/fisiología , Homocisteína/sangre , Óxido Nítrico Sintasa de Tipo III/genética , Adulto , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético
6.
Nefrologia ; 26(6): 666-72, 2006.
Artículo en Español | MEDLINE | ID: mdl-17227243

RESUMEN

Adult dominant polycystic kidney disease is an hereditary condition responsible for 6% of end-stage renal failure in Spain. Two genes were located in chromosomes 16 and 4 as related to this age-dependent disease in the 90s (PKD1 and PKD2). The diagnosis can be easily achieved by sonographic study, but molecular analysis by means of linkage analysis has the advantage of an early diagnosis in asymptomatic genetic carriers, with a view to the preventive follow-up of these subjects and genetic counselling. In this paper we present the results of molecular analysis of 30 families with Adult Dominant Polycystic Kidney Disease (from the province of Las Palmas Spain), carried out linkage analysis with two series of microsatellite markers located within or in the vicinity ofPKD1 (D16S521, KG8, AC2.5, CW2, SM7) and PKD2 (D4S1538, D4S1534, D4S423,D4S414) genes. The objectives of the study were: first, to verify the informativeness, and therefore, the usefulness of these markers for family studies in our population; and second,to assess the sensitivity and specificity of the genetic analysis in our population. Most of the markers showed a high heterozygosity, comparable to data in other studies. Considering the alleles of the different markers together in a chromosome as an haplotype increased the informativeness of the markers, and allowed the unequivocal identification of genetic data in 97.7% of patients and 88.7% of healthy subjects. The sensitivity and specificity of the genetic analysis were 90.7% (CI 95%: 85.7-95.7) and 86.8% (CI 95%: 80.6-93.0), respectively.


Asunto(s)
Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 16/genética , Riñón Poliquístico Autosómico Dominante/diagnóstico , Canales Catiónicos TRPP/análisis , Islas del Atlántico/epidemiología , Diagnóstico Precoz , Tamización de Portadores Genéticos , Marcadores Genéticos , Haplotipos/genética , Humanos , Hipertensión Renal/epidemiología , Hipertensión Renal/etiología , Escala de Lod , Repeticiones de Microsatélite , Riñón Poliquístico Autosómico Dominante/epidemiología , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/terapia , Diálisis Renal , Sensibilidad y Especificidad
7.
J Am Coll Cardiol ; 37(6): 1536-42, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11345362

RESUMEN

OBJECTIVES: We examined the relationship between the angiotensinogen (AGT) gene M235T polymorphism, the variant promoter of the AGT gene A(-6)G and the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary heart disease (CHD) in native Gran Canaria Island habitants, who have the highest rates of CHD in Spain. BACKGROUND: Some studies subject that the ACE (I/D) polymorphism could be associated with CHD, while AGT (M235T) has been related to essential hypertension. METHODS: We studied 304 subjects with angiographic evidence of coronary artery disease and a clinical diagnosis of myocardial infarction or unstable angina and 315 age- and gender-matched controls. Blood was drawn and DNA extracted. Angiotensin-converting enzyme (I/D) gene polymorphism was analyzed by polymerase chain reaction (PCR) and AGT gene polymorphisms by restriction fragment length polymorphism-PCR and mutagenically-separated PCR. RESULTS: The ACE (I/D) polymorphism showed no association with CHD, whereas the frequency distribution of AGT (M235T) genotypes among patients and controls (235T: 29.1% and 19.0%; M235T: 48.5% and 50.2%; M235: 22.4% and 30.8%, respectively) was statistically different (p = 0.005) and not related to the presence of essential hypertension. Similar results were observed with the AGT A(-6)G polymorphism. In multiple logistic regression analysis, CHD odds ratio associated with 235T and M235 homozygotes were 1.7 (1.1 to 2.6) and 0.54 (0.36 to 0.82), respectively. CONCLUSIONS: This study shows that genetic variation of the AGT (M235T), but not the ACE (I/D), genotypes contributes to the presence of CHD independently of blood pressure profile in a subset of the Spanish population with a high prevalence of cardiovascular disease.


Asunto(s)
Angina Inestable/genética , Angiotensinógeno/genética , Enfermedad Coronaria/genética , Eliminación de Gen , Variación Genética/genética , Mutagénesis Insercional/genética , Infarto del Miocardio/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Adulto , Anciano , Angina Inestable/sangre , Angina Inestable/diagnóstico , Angina Inestable/epidemiología , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/epidemiología , Femenino , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Genotipo , Homocigoto , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Prevalencia , Regiones Promotoras Genéticas/genética , Radiografía , Sistema Renina-Angiotensina/genética , Factores de Riesgo , España/epidemiología
8.
Nefrologia ; 25(5): 500-8, 2005.
Artículo en Español | MEDLINE | ID: mdl-16392299

RESUMEN

UNLABELLED: Arterial hypertension and diabetes mellitus give rise to a situation of high cardiovascular risk. The potential renoprotection from inhibition of the renin-angiotensin system is a valid option in this type of patient. OBJECTIVE: Evaluate the effect of valsartan on blood pressure (BP) and renal function in albuminuric patients with type 2 diabetes and arterial hypertension. PATIENTS AND METHODS: This was a prospective, observational study. Seventy-four diabetic patients with a blood pressure of > or = 140/90 mmHg, with micro or macroalbuminuria and a) blood creatinine levels lower 1.5 mg/dl (group 1) or b) blood creatinine levels between 1.5 and 2 mg/dl (group 2), were studied and followed up for a 12-week period. Treatment was started with valsartan 80 mg/d, increasing to 160 mg/d, adding torasemide at a dose of 5 mg/d if the target blood pressure of 130/85 mmHg has not been achieved. The degree of BP reduction was analyzed comparatively using a mercury sphygmomanometer and a semi-automatic monitor, the Omron HEM 705 CP. RESULTS: All patients showed a significant reduction of the systolic (SBP) and diastolic (DBP) blood pressures (p< 0.001) over the study period, decreasing from 150.7 +/- 12.8 to 130.8 +/- 9.6 and from 94.7 +/- 7.7 to 76.8 +/- 6.3 mmHg, respectively. A significant reduction was observed only for diastolic blood pressure (101.4 +/- 8.8 to 79.4 +/- 5.6; p < 0.001) in the group 2 of patients. Lowest BP values were always obtained with the semiautomatic device. At the end of the study, 9.5% maintained valsartan 80 mg/d and 36.5% reqcuired the addition of a second or third drug to valsartan 160 mg in order to achieve the therapeutic target BP A significant reduction was observed in the microalbuminuria (75.5 +/- 9.5 to 54.7 +/- 7.3 microg/min; p < 0.001) and macroalbuminuria (n = 20; 0.93 +/- 0.4 to 0.68 +/- 0.4 g/day; p < 0.001). CONCLUSION: Valsartan significantly reduced SBP and DBP Valsartan at 160 mg/d had a significantly greater effect in reducing micro and macroalbuminuria. No changes were observed in renal function, HbA1c or serum potassium. The rate of adverse events was very low.


Asunto(s)
Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/complicaciones , Angiopatías Diabéticas/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Tetrazoles/uso terapéutico , Valina/análogos & derivados , Adulto , Anciano , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Valina/uso terapéutico , Valsartán
9.
J Hum Hypertens ; 15(12): 849-56, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11773987

RESUMEN

The objective of this study was to compare, at equal blood pressure (BP) reduction, the effect of two different combinations on metabolic control and albuminuria in type 2 diabetic hypertensive patients with albuminuria. This was a prospective, randomised, double-blind, parallel, controlled trial carried out in 11 Spanish hospitals. A total of 103 type 2 diabetic patients with stable albuminuria and BP not controlled on monotherapy were randomised of which 93 finished the study. After a 4-week single-blind placebo period, patients were randomised to verapamil SR/trandolapril 180/2 mg (VT) or to enalapril/hydroclorothiazide 20/12.5 mg (EH). Treatment duration was 6 months. The main outcome measures were changes in BP, 24-h albuminuria, blood glucose and glycated haemoglobin. Overall BP was significantly reduced from 157.3 +/- 12.0/98.3 +/- 6.4 mm Hg to 140.5 +/- 14.5/86.1 +/- 8.2 mm Hg (P < 0.001) and albuminuria significantly decreased from 508.6 +/- 693.8 mg/24 h to 253.4 +/- 517.2 mg/24 h (P < 0.001), both without significant differences between treatments. Glycated haemoglobin was not modified on VT: baseline, 5.91 +/- 1.43%; end of treatment, 5.94 +/- 1.62%, but increased on EH: baseline, 5.96 +/- 1.25%; final, 6.41 +/- 1.51%, (ANOVA interaction P = 0.040). At the end of the study, a blood glucose <126 mg/dL was attained in 72.7% of the VT group-improving in 29.5% and worsening in 6.8% of patients (P = 0.021)-and in 50% of the EH group, 13.6% of patients improved and 11.4% worsened (P = 1.000). There were no changes in body weight, serum creatinine, uric acid, potassium, cholesterol, tryglicerides and serum albumin. In hypertensive type 2 diabetic patients not controlled on monotherapy, both treatments similarly reduced albuminuria. The combination verapamil/ trandolapril seems to allow a better metabolic control than enalapril/hydroclorothiazide.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Enalapril/administración & dosificación , Hidroclorotiazida/administración & dosificación , Hipertensión/tratamiento farmacológico , Indoles/administración & dosificación , Verapamilo/administración & dosificación , Anciano , Albuminuria/complicaciones , Albuminuria/tratamiento farmacológico , Albuminuria/metabolismo , Análisis de Varianza , Antihipertensivos/administración & dosificación , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/complicaciones , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Probabilidad , Estudios Prospectivos , España , Resultado del Tratamiento
10.
J Hum Hypertens ; 14(12): 789-93, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11114694

RESUMEN

Angiotensinogen (AGT) gene polymorphism has shown significant differences in the allelic frequencies between hypertensive and normotensive subjects. This allele frequency varies among ethnic groups. There are still some controversies related to the 235T-variant as a marker for essential hypertension. As part of an extensive case-control study carried out in a Spanish population, we selected the 237 subjects with a diagnosis of essential hypertension according to the established criteria. A group of 242 normotensives matched for age and gender was used as control. Smoking habits, a previous diabetes and hypertension medical history, body mass index (BMI) and blood pressure (BP) values were recorded. Glucose, plasma creatinine, lipid profile with Lp(a), homocysteine and microalbuminuria were measured. Angiotensinogen M235T-gene polymorphism was determined by polymerase chain reaction (PCR) from genomic DNA. A(-6)G polymorphism was determined by mutagenically separated PCR (MS-PCR). BP values, BMI and microalbuminuria were significantly higher in hypertensive subjects; 31.6% of hypertensives and 40.1% normotensives were active smokers. M235T-genotype frequencies were not different in the hypertensive and normotensive population. Similarly, homocigotic AA predominate in the hypertensives but without statistical significance. The association of 235T-genotype or the changes in the promoter activity due to A(-6) substitution with essential hypertension was not confirmed in the multivariate regression analyses. Only a previous family history of hypertension and BMI were significantly associated with hypertension. Journal of Human Hypertension (2000) 14, 789-793


Asunto(s)
Angiotensinógeno/genética , Presión Sanguínea , Polimorfismo Genético , Anciano , Alelos , Femenino , Homocisteína/sangre , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
11.
J Physiol Biochem ; 54(3): 127-33, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10217208

RESUMEN

Nitric oxide (NO) controls blood pressure and plays a role in the water and sodium handling by the kidneys. Inhibition of NO synthesis with competitive L-arginine analogues leads to increased renal vascular resistance and raised systemic and glomerular blood pressure. The effects of chronic NO-synthesis inhibition by N(G)-nitro L-arginine methyl-esther (L-NAME) in the disposal of an acute NaCl load are studied on fourteen male Munich-Wistar rats. Eight of which were given L-NAME (100 mg/L) in the drinking water for 21 days. Six control rats differed only in not receiving L-NAME. As expected, significant hypertension and a marked renal vasoconstriction were accompanied by a decline in renal plasma flow, without changes in glomerular filtration rate, with filtration fraction thus being increased in the NO-blocked rats. In the basal state there was no significant reduction of sodium urinary excretion in the L-NAME treated rats. Both groups of rats elicited an increase in urinary sodium excretion after the NaCl load which was initially more evident and longer in the L-NAME treated group. The ratio of Na+ excreted to Na+ infused was similar between the groups. This observation suggests that in this model of chronic inhibited NO rats, the disposal of an acute sodium load is reached. The existence of a delayed mechanism in renal excretion of Na+ by the chronic NO-blocked rats could be suggested.


Asunto(s)
Hipertensión/metabolismo , Riñón/metabolismo , Óxido Nítrico/biosíntesis , Cloruro de Sodio/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Peso Corporal/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Hipertensión/tratamiento farmacológico , Riñón/efectos de los fármacos , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/antagonistas & inhibidores , Ratas , Ratas Wistar , Sodio/orina , Cloruro de Sodio/farmacología
12.
Adv Perit Dial ; 8: 376-80, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1361827

RESUMEN

CAPD is considered a risk factor for low turnover bone disease. This was previously attributed to aluminum accumulation. We evaluated by biochemical and histomorphometric parameters (including double tetracycline labelling), 26 patients maintained on CAPD for 12-14 months. Three (11.5%) showed mild hyperparathyroidism, 5 (19.2%) osteitis fibrosa, 3 (11.5%) mixed forms, 4 (15%) osteomalacia and 11 (42.3%) adynamic bone disease. Only one patient with diabetes mellitus showed an aluminum stained bone surface > 10%. Intact PTH serum levels were lower in LTBD (133.2 +/- 128 vs 468.2 +/- 451 pg/ml; p < 0.05). We also evaluated prospectively 11 patients who underwent a bone biopsy at start of dialysis and after 12 months of CAPD treatment. Bone biopsies pre CAPD demonstrated normal-high bone turnover disease in 8/11 (72.7%) and low turnover bone disease in 3/11 (27%). In the follow-up biopsies, 2 patients showed osteitis fibrosa and other two mild forms. Low turnover bone disease was found in 7 patients (3 osteomalacia and 4 adynamic bone disease). We conclude that the predominant bone lesion in our CAPD patients is low turnover bone disease, predominantly adynamic forms, and aluminum does not seem to play a role on its genesis. Low intact PTH serum levels may be a predictor of low turnover bone disease.


Asunto(s)
Huesos/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/etiología , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Huesos/patología , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteomalacia/etiología , Hormona Paratiroidea/sangre , Estudios Prospectivos , Factores de Riesgo
13.
Nefrologia ; 22 Suppl 1: 80-8, 2002.
Artículo en Español | MEDLINE | ID: mdl-11987675

RESUMEN

Molecular biology techniques have provided important advances in the search for causal relationships in complex diseases supporting traditional epidemiologic studies. Genetic epidemiology allows us to detect genetic variants that could be related to the onset and progression of different diseases. In cardiovascular and renal diseases, this approach linking traditional risk factors to new described ones and those allelic variants, which contribute to the development of these manifestations permits a better understanding of individual disease susceptibility. This is usually afforded through case-control studies evaluating allelic variants of candidate genes previously associated with the disease. Even in this candidate gene search, association-based methods are more powerful than linkage studies in complex traits if we assume that some of the typed polymorphisms are causative although with subtle phenotypic effects. Some brief examples may illustrate the progress in the understanding of renal and cardiovascular diseases.


Asunto(s)
Enfermedades Renales/genética , ADN/análisis , Técnicas Genéticas , Humanos , Hipertensión/genética , Nefritis Hereditaria/genética , Reacción en Cadena de la Polimerasa , ARN/análisis , Tumor de Wilms/genética
14.
Nefrologia ; 21(5): 456-63, 2001.
Artículo en Español | MEDLINE | ID: mdl-11795014

RESUMEN

The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil significant lowered albuminuria and blood pressure facilitated the control or their metabolic profile.


Asunto(s)
Albuminuria/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Indoles/administración & dosificación , Verapamilo/administración & dosificación , Albuminuria/etiología , Diabetes Mellitus Tipo 2/complicaciones , Quimioterapia Combinada , Femenino , Humanos , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos
15.
Nefrologia ; 21(1): 52-8, 2001.
Artículo en Español | MEDLINE | ID: mdl-11344962

RESUMEN

Hypertensive mechanisms are postulated to play a major role in the progressive glomerulosclerosis (GS) after renal mass reduction. Previous studies have demonstrated differences in the progression to glomerulosclerosis with the use of different antihypertensive drugs. We analyzed whether the use of carvedilol (CVD), a new beta-adrenoceptor antagonist and vasodilator slows the progression of glomerulosclerosis in 5/6 nephrectomised (Nx) rats. Fifty-four adult Sprague-Dawley rats were distributed among five groups, four with 5/6 Nx, vehicle treated and CVD at 5, 10 and 20 mg/kg/day and sham (no renal ablation or drug treatment). Tailcuff blood pressure, serum creatinine and urine protein concentration were measured. At the end of the experiment remnant kidney was removed for morphometric studies. Rats treated with 10 and 20 mg/kg/day of CVD showed controlled systemic blood pressure. Serum creatinine was similar in all treated groups with CVD, and half the levels observed in the vehicle-treated rats. The prevalence of glomerular lesions was closely associated with the degree of proteinuria. Eleven weeks after 5/6 Nx, vehicle-treated rats exhibited marked GS with 76% of affected glomeruli and creatinine retention. By contrast, renal injury was largely prevent in those rats treated with 10 and 20 mg/kg/day of CVD. Tuft enlargement occurred in all groups but was more prominent in vehicle-treated group, 1.5 times higher than the group treated with 20 mg/kg/day of CVD. Although, these data demonstrate the importance of systemic blood pressure control in the renal protective efficacy of carvedilol, other less-known mechanisms of this drug must be investigated.


Asunto(s)
Antihipertensivos/uso terapéutico , Carbazoles/uso terapéutico , Fallo Renal Crónico/tratamiento farmacológico , Propanolaminas/uso terapéutico , Animales , Carvedilol , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Sprague-Dawley
16.
Med Clin (Barc) ; 101(2): 45-50, 1993 Jun 05.
Artículo en Español | MEDLINE | ID: mdl-8510475

RESUMEN

BACKGROUND: As a fruit of complex interaction of factors, coronary atherosclerosis constitutes the first cause of death in the developed countries. METHODS: With the aim of studying the risk factors of ischemic cardiopathy in a natural adult population (30-64 years) from Lanzarote (Canary Islands) a representative sample of 600 individuals was studied with participation of 70% being obtained. RESULTS: The prevalences obtained were the following: established arterial hypertension (systolic: 160 mmHg and/or diastolic 95 mmHg) 24%; hypercholesterolemia (cholesterol: 6.5 mmol) 25%; diabetes (basal glucose: 7.8 mmol) 6.1%; hypertriglyceridemia (triglycerides 2.3 mmol) 12%; cholesterol (lipids and high density lipoproteinemia HDL) lower than 0.90 mmol in males 19% and lower than 1.16 mmol in females 36%; male smoking habit 53%; female smoking habit 15%; obesity (Quetelet index: 30) male 19%, females 35%, family history of ischemic cardiopathy (prior to 60 years of age) 14%; use of oral contraceptives in premenopausic females 13%; left ventricular growth in hypertensive individuals 7.4%. CONCLUSIONS: The prevalence of cardiovascular risk factors is high for arterial hypertension, diabetes, hypercholesterolemia, male smoking habit and female obesity. These results demonstrate an unfavorable profile for cardiovascular risk in the population of Lanzarote and it is reasonable to assume that this may be due to the great socioeconomic growth which has taken place on the island over the last decade.


Asunto(s)
Isquemia Miocárdica/epidemiología , Adulto , Islas del Atlántico/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo
17.
Med Clin (Barc) ; 108(10): 366-72, 1997 Mar 15.
Artículo en Español | MEDLINE | ID: mdl-9139142

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the clinical results analyzing the cure, improvement and failure rates of percutaneous transluminal angioplasty (PTA) in patients with the diagnosis of renovascular hypertension with special reference to those with atherosclerotic vascular disease, according to their age, and their effect on blood pressure control and renal function. PATIENTS AND METHODS: In 93 hypertensive patients with a mean age of 43.4 years 123 renal artery PTA were performed: Twenty-six patients older than 50 years and eleven with 50 years or less had atherosclerosis, 27 fibromuscular dysplasia and a mixed disease was found in one patient. Twenty-eight patients with renal transplant were diagnosed as having arterial graft stenosis. RESULTS: After renal PTA, there was a significant decrease in blood pressure in all cases. Patients with atherosclerotic renal vascular disease showed a decrease in systolic pressure (SP) from 168 +/- 19 before PTA to 154 +/- 8 mmHg at 96 months (p < 0.001) and diastolic (DP) from 113 +/- 10 before PTA to 90 +/- 4 mmHg at 96 months (p < 0.001) respectively after the procedure. Significant differences were also observed in patients with fibromuscular dysplasia. Most patients with renal transplant arterial stenosis had less than five years of follow-up and SP and DP decreased from 162 +/- 18 and 109 +/- 8 mmHg before PTA, to 147 +/- 10 (p < 0.001) and 91 +/- 7 mmHg (p < 0.001) at 12 months after dilation respectively. Clinical improvement was achieved in 91% of patients with atherosclerosis at 96 months and fifty percent of the patients with fibromuscular dysplasia were cured after the same period from the time of PTA. Twelve months after the renal transplant artery dilation was achieved a clinical improvement in 81% and a cure rate in 6% of the patients. Ostial lesions comprised the majority of blood pressure benefit failures. There was no significant improvement in renal function immediately after renal artery dilation except in those patients with fibromuscular dysplasia. Residual stenosis greater than 75% was present in 15 patients after the first PTA. Complications were seen in 4.8% and were related to renal failure and vessel dissection. CONCLUSION: Angioplasty is effective in the long-term management of high arterial blood pressure and may preserve renal function according to renal artery disease.


Asunto(s)
Angioplastia de Balón , Presión Sanguínea , Riñón/fisiopatología , Obstrucción de la Arteria Renal/terapia , Anciano , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/métodos , Angioplastia de Balón/estadística & datos numéricos , Arteriosclerosis/complicaciones , Arteriosclerosis/fisiopatología , Arteriosclerosis/terapia , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Renovascular/etiología , Hipertensión Renovascular/fisiopatología , Hipertensión Renovascular/terapia , Masculino , Persona de Mediana Edad , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/fisiopatología , Factores de Tiempo , Insuficiencia del Tratamiento
18.
An Med Interna ; 9(9): 428-32, 1992 Sep.
Artículo en Español | MEDLINE | ID: mdl-1391577

RESUMEN

Q fever is an endemic zoonosis in the Canary Islands. In 1986, we detected, in a pilot study, residual antibodies of the infection in 3% of the population from Lanzarote. In 1989, we performed a new study in order to assess seroprevalence of Q fever among the adult native population from the island. We studied 390 human serums obtained from an statistically representative sample. Age ranged from 30 to 64 years. Out of 390 serums, 196 (50.25%) were obtained from men and 194 (49.74%) from women. The serological technique used was the fixation of complement using Coxiella burnetii antigens in phase II. Titres equal or higher than 1/8 were considered positive. No statistically significant differences were observed with regard to seroprevalence rates considering sex, age, nor living in or outside the island's capital city. However, when dividing the island's territory in three areas (north, centre and south), and assessing independently their respective seroprevalences, we observed relatively higher seroprevalences in the furthest areas (13.3% in the north and 13.5% in the south) than in the central area (4.7%), although only the higher seroprevalence in the south reached statistical significance when compared with the mean prevalence. Probably, these observations indicate that, although Q fever is extended all over the island, it is a more frequent infection in rural areas of Lanzarote, at the north and the south, than in the central area, where the main urban areas are located.


Asunto(s)
Fiebre Q/epidemiología , Adulto , Islas del Atlántico/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos
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