[HDL cholesterol and cardiovascular disease in a population with hypertension and type 2 diabetes mellitus. RICARHD Study]. / Colesterol HDL y enfermedad cardiovascular en una población con hipertensión y diabetes mellitus tipo 2. Estudio RICARHD.

OBJECTIVE: To assess the prevalence of low serum levels of HDL cholesterol (HDL-C) and its relationship with the presence of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) and arterial hypertension attended in Internal Medicine and Nephrology offices. METHODS: Cross-sectional, multicenter study, conducted in diabetic patients with hypertension, aged >/= 55 years old. Demographic, clinical and biochemical data were obtained from the patient's hospital records. Low HDL-C was defined as <40 mg/dl (men) or <46 mg/dl (women). The relationship between low HDL-C and CVD was assessed using logistic regression models. RESULTS: In 2,021 patients (mean age: 68.6 years, 48.9% women, 51.1% with established CVD), the prevalence of low HDL-C was 33.7% (95% CI: 31.5-35.7), it being higher in women (38.0%) than in men (29.6%, p<0.001), and higher in patients with previous CVD (37.3% vs. 29.9% in patients without CVD, p=0.001). In the multivariate analysis that included cardiovascular risk factors, an independent relationship between low HDL-C levels and CVD was observed (OR for CVD in patients with low HDL-C: 1.46 [CI 95%: 1.19-1.79, p<0.001]), compared to patients with normal HDL-C blood levels. A second model which was also adjusted for left ventricular hypertrophy and renal disease showed a similar association (OR 1.55 [1.21-2.00], p=0.001). This association was stronger in women than in men. CONCLUSIONS: One out of three patients with diabetes and hypertension examined in Internal Medicine and Nephrology outpatient offices had low serum levels of HDL-C. Low HDL-C showed an independent relationship with a higher prevalence of CVD.

Colesterol HDL y enfermedad cardiovascular en una población con hipertensión y diabetes mellitus tipo 2. Estudio RICARHD / HDL cholesterol and cardiovascular disease in a population with hypertension and type 2 diabetes mellitus. RICARHD Study

Objetivo: Evaluar la prevalencia del colesterol HDL (c-HDL) bajo y su asociación con la presencia de enfermedad cardiovascular (ECV) en pacientes con diabetes mellitus (DM) tipo 2 e hipertensión arterial atendidos en consultas de medicina interna y nefrología. Métodos: Estudio transversal multicéntrico, realizado en diabéticos hipertensos de 55 años o más. Los datos demográficos, clínicos y bioquímicos se recogieron de las historias clínicas. Se definió el c-HDL bajo como inferior a 40 mg/dl (varones) e inferior a 46 mg/dl (mujeres). Se valoró la asociación entre c-HDL bajo y ECV mediante modelos de regresión logística. Resultados: En 2.021 pacientes (edad media 68,6 años; 48,9% mujeres; 51,1% con ECV establecida), la prevalencia de c-HDL bajo fue del 33,7% (intervalo de confianza [IC] 95%: 31,5-35,7), mayor en mujeres (38,0%) que en varones (29,6%, p<0,001) y mayor en los pacientes con ECV (37,3% frente a 29,9% en sujetos sin ECV, p=0,001). En un análisis multivariante que incluyó los factores de riesgo cardiovascular se observó una asociación independiente entre c-HDL bajo y ECV (odds ratio [OR] para ECV en sujetos con c-HDL bajo: 1,46 [1,19-1,79; p<0,001], respecto a sujetos con c-HDL normal). Un segundo modelo ajustado, además, por la hipertrofia ventricular izquierda y el daño renal mostró una asociación similar (OR 1,55 [1,21-2,00], p=0,001). La magnitud de la asociación fue superior en la mujer que en el hombre. Conclusiones: Uno de cada tres diabéticos hipertensos atendidos en consultas de medicina interna y nefrología presentó una concentración baja de c-HDL. La concentración baja de c-HDL se asoció, de forma independiente, a una mayor prevalencia de ECV (AU)

Objective To assess the prevalence of low serum levels of HDL cholesterol (HDL-C) and its relationship with the presence of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) and arterial hypertension attended in Internal Medicine and Nephrology offices. Methods Cross-sectional, multicenter study, conducted in diabetic patients with hypertension, aged ≥ 55 years old. Demographic, clinical and biochemical data were obtained from the patient's hospital records. Low HDL-C was defined as <40 mg/dl (men) or <46 mg/dl (women). The relationship between low HDL-C and CVD was assessed using logistic regression models. Results: In 2,021 patients (mean age: 68.6 years, 48.9% women, 51.1% with established CVD), the prevalence of low HDL-C was 33.7% (95% CI: 31.5-35.7), it being higher in women (38.0%) than in men (29.6%, p<0.001), and higher in patients with previous CVD (37.3% vs. 29.9% in patients without CVD, p=0.001). In the multivariate analysis that included cardiovascular risk factors, an independent relationship between low HDL-C levels and CVD was observed (OR for CVD in patients with low HDL-C: 1.46 [CI 95%: 1.19-1.79, p<0.001]), compared to patients with normal HDL-C blood levels. A second model which was also adjusted for left ventricular hypertrophy and renal disease showed a similar association (OR 1.55 [1.21-2.00], p=0.001). This association was stronger in women than in men. Conclusions: One out of three patients with diabetes and hypertension examined in Internal Medicine and Nephrology outpatient offices had low serum levels of HDL-C. Low HDL-C showed an independent relationship with a higher prevalence of CVD (AU)

[Vascular damage in chronic renal failure. The increase of vascular nitrotyrosine and cytochines accumulation is accompanied by an increase of endothelial nitric oxide synthase (eNOS) expression]. / Daño vascular en la insuficiencia renal crónica. El aumento de depósitos vasculares de nitrotirosina y citocinas se acompaña de una elevación de la expresión vascular de la óxido nítrico sintasa endotelial (eNOS).

Patients with chronic renal failure (CRF) are at a greatly increased risk of cardiovascular mortality. This fact could be due to the presence of conventional risk factor and specific uremic as increase of oxidative stress, hyperhomocystaenemia, deranged calcium-phosphate metabolism and chronic inflammatory state. In order to analyze the vascular effects of CRF, we studied the histomorphometric characteristics (intima-media thickness and monocyte chemoattractant protein (MCP-1) accumulation (inmunohistochemical) on radial artery from 13 patients with CRF. We determined by Western blot analysis, the vascular nitrotyrosin abundance (footprint of nitric oxide (NO) inactivation by reactive oxygen species (ROS), and the endothelial nitric oxide synthase (eNOS) expression. The NOS activity was, also, determined. The results were compared with those obtained in pudenda artery from a healthy control group (n: 16). The CRF group showed a significant increase in intima and media thickness 108 +/- 16 vs 14 +/- 2.5 microm, p < 0.001 and 291 +/- 19 vs 153 +/- 15 microm, p < 0.001, respectively). The CRF group exhibited a marked elevation of MCP-1 vascular expression (2 +/- 0.15 vs 0.6 +/- 0.12 u, p < 0.001). A significant positive correlation was found between MCP-1 vascular expression and its inmunohistochemical deposits (r: 0.98, p < 0.0001). Nitrotyrosin abundance (western blot) was significantly increased in artery of CRF patients (2.1 +/- 0.1 vs 0.42 +/- 0.1 u, p < 0.0001). No significant differences was found in NOS activity between CRF and control groups. However, eNOS expression was greatly increased in the CRF patients (1.73 +/- 0.1 vs 0.67 +/- 0.1 u, p < 0.001). A significant positive correlation was found between nitrotyrosin and eNOS expression and systolic arterial pressure. However, the differences between CRF and control groups persisted after statistically fitting to arterial pressure. The present study demonstrate that in CRF there are arterial preatherosclerotic changes and an increase of vascular nitrotyrosin accumulation, which is the footprint of NO inactivation by ROS. The secondary NO inactivation can, in turn, contribute to eNOS vascular upregulation.

Daño vascular en la insuficiencia renal crónica. El aumento de depósitos vasculares de nitrotirosina y citocinas se acompaña de una elevación de la expresión vascular de la óxido nítrico sintasa endotelial (eNOS) / Vascular damage in chronic renal failure. The increase of vascular nitrotyrosine and cytochines accumulation is accompanied by an increase of endothelial nitric oxide synthase (ENOS) expression

La insuficiencia renal crónica (IRC) se acompaña de un aumento de la morbimortalidadcardiovascular debido a la concurrencia de factores de riesgo cardiovasculartradicionales y otros factores inherentes a la uremia como estrés oxidativo,hiperhomocisteinemia, anomalías del metabolismo fosfocálcico, anemia yfenómenos inflamatorios entre otros.Para analizar la repercusión vascular de la IRC, en este trabajo se hace un estudiohistomorfométrico (grosor íntima-media) y de los depósitos vasculares (inmuno-histoquímica) de la proteína quimiotáctica de monocitos (MPC-1) de la arteriaradial en 13 sujetos con IRC, Se determinan, también, la expresión vascular(western blot) de nitrotirosina (marcador del efecto de especies reactivas de oxígeno(ROS) sobre el óxido nítrico (ON), de la MCP-1 (citocina con efecto aterogénico)y de la óxido nítrico sintasa endotelial (eNOS), y la actividad de la NOS.Los hallazgos se comparan con los observados en la arteria pudenda, arteria muscularde las mismas características que la radial, en un grupo control sano (n: 16),de edad y sexo similares a los enfermos.El grosor de la íntima y de la media fue mayor en los enfermos (íntima 108 ±16 vs 14 ± 2,5 µ, p < 0,001; media: 291 ± 19 vs 153 ± 15 µ, p < 0,001). La expresiónvascular de la MCP-1 en los enfermos fue más elevada que en los controles(2 ± 0,15 vs 0,6 ± 0,12 u, p < 0,001). La expresión de la proteína se correlacionócon los depósitos inmunohistoquímicos de la misma (r: 0,98, p <0,0001). Las arterias de los enfermos con IRC tenían mayor expresión de nitrotirosinaque las de los sujetos sanos (2,1 ± 0,1 vs 0,42 ± 0,1 u, p < 0,0001). Noexistieron diferencias significativas en la actividad de la NOS entre los dos grupos.La expresión de la eNOS, sin embargo, fue significativamente más elevada enlos enfermos con IRC (1,73 ± 0,1 vs 0,67 ± 0,1 u, p < 0,001). La expresión dela nitrotirosina y de la eNOS se correlacionó directamente con la presión arterial sistólica. No obstante, las diferencias entre los grupos persistieron tras los ajustesa los valores de presión arterial.Estos resultados demuestran que en la IRC, a nivel de la arteria radial, existencambios preaterosclerosos, y un aumento de los depósitos de nitrotirosina, marcadordel efecto de ROS sobre el ON. Secundariamente a la disminución de labioactividad del ON, se produce un aumento compensador de la expresión vascularde la eNOS

Patients with chronic renal failure (CRF) are at a greatly increased risk of cardiovascularmortality. This fact could be due to the presence of conventional riskfactor and specific uremic as increase of oxidative stress, hyperhomocystaenemia,deranged calcium-phosphate metabolism and chronic inflammatory state.In order to analyce the vascular effects of CRF, we studied the histomorphometriccharacteristics (intima-media tickness and monocyte chemoattractant protein(MCP-1) accumulation (inmunohistochemical) on radial artery from 13 patientswith CRF. We determined by Western blot analysis, the vascular nitrotyrosinabundance (footprint of nitric oxide (NO) inactivation by reactive oxygen species(ROS), and the endothelial nitric oxide synthase (eNOS) expression. The NOS activitywas, also, determined. The results were compared with those obtained inpudenda artery from a healthy control group (n: 16).The CRF group showed a significant increase in intima and media tickness 108± 16 vs 14 ± 2,5 µ, p < 0,001 and 291 ± 19 vs 153 ± 15 µ, p < 0,001, respectively).The CRF group exhibited a marked elevation of MCP-1 vascular expression(2 ± 0,15 vs 0,6 ± 0,12 u, p < 0,001). A significant positive correlationwas found between MCP-1 vascular expression and its inmunohistochemical deposits(r: 0,98, p < 0,0001). Nitrotyrosin abundance (western blot) was significantlyincreased in artery of CRF patients (2,1 ± 0,1 vs 0,42 ± 0,1 u, p < 0,0001).No significant differences was found in NOS activity between CRF and controlgroups. However, eNOS expression was greatly increased in the CRF patients(1,73 ± 0,1 vs 0,67 ± 0,1 u, p < 0,001). A significant positive correlation wasfound between nitrotyrosin and eNOS expression and systolic arterial pressure.However, the differences between CRF and control groups persisted after statisticallyfitting to arterial pressure.The present study demonstrate that in CRF there are arterial preatheroscleroticchanges and an increase of vascular nitrotyrosin accumulation, wich is the footprintof NO inactivation by ROS. The secondary NO inactivation can, in turn, contributeto eNOS vascular upregulation

Intervención sobre el sistema renina-angiotensina para la protección vascular del paciente hipertenso y en la nefropatía diabética / Modulation of renin-angiotensin system for vascular protection in hypertensive patients and in patients with diabetic nephropathy

La angiotensina II interviene en la génesis de la hipertensión arterial y en el daño orgánico que acompaña a la hipertensión arterial y a la diabetes mellitus. Por sus efectos proinflamatorios, la angiotensina II participa en el proceso de aterogénesis. En la hipertrofia ventricular izquierda que acompaña a la hipertensión arterial intervienen mecanismos hemodinámicos y diversas citocinas cuya producción es estimulada por la angiotensina II. La angiotensina II también contribuye al daño renal secundario a la diabetes mellitus por sus acciones en la hemodinámica intraglomerular y por sus efectos fibrogénicos glomerulares e intersticiales. La intervención sobre el sistema renina-angiotensina debe formar parte de la terapia del enfermo con elevado riesgo cardiovascular con enfermedad hipertensiva y/o diabetes mellitus (AU)

[Modulation of renin-angiotensin system for vascular protection in hypertensive patients and in patients with diabetic nephropathy]. / Intervención sobre el sistema renina-angiotensina para la protección vascular del paciente hipertenso y en la nefropatía diabética.

Angiotensin II intervenes in the genesis of arterial hypertension and in the organic damage associated to arterial hypertension and to diabetes mellitus. Because of its proinflammatory effects, angiotensin II participates in the process of atherogenesis. Hemodynamic mechanisms and several citokines whose production is promoted by angiotensin II participate in left ventricular hypertrophy associated to arterial hypertension. Angiotensin II also contributes to renal damage secondary to diabetes mellitus by its actions in the intraglomerular hemodynamics and by its glomerular and interstitial fibrogenic effects. The intervention on the renin-angiotensin system should be part of therapy of patients with high cardiovascular risk with hypertensive disease and/or diabetes mellitus.

[Hormonal profile and participation of nitric oxide in salt-sensitive and salt-resistant essential arterial hypertension]. / Perfil hormonal y participación del óxido nítrico en la hipertensión arterial esencial "sal sensible" y "sal resistente".

Recent studies have shown that cardiovascular events and end-organ damage occur more frequently in patients with salt-sensitive essential hypertension (SH) than in salt-resistant essential hypertension (RH). Nitric oxide (NO) plays an important role in regulating the pressure-natriuresis relationship. Therefore impaired NO synthesis may produce or aggravate salt-sensitive hypertension. This study was conducted to determine the hormonal levels and nitric oxide metabolites in hypertensive patients. 25 patients underwent salt sensitivity testing. 24 h ambulatory blood pressure was recorded after a 5-day period on low salt diet (20 mEq/d) and after a 5-day period on a high salt diet (200 mEq/d). Subjects showing > or = 10 mmHg increase in mean BP when changing from low to high dietary salt intake were classified as salt sensitive and as salt resistant when the BP changes were < 10 mmHg. Based on BP recordings 13 patients were characterised as white coat hypertension (WC), 13 patients as salt resistant (SR) and 12 as salt sensitive (SS). A significative relationship was seen between plasma glucose-insulin concentration and body mass index. The ventricular mass index was similar in SS and SR patients. The plasma uric acid, triglicerides and PAI-I were elevated in SS compared with SR, and control group (C). During low sodium intake, plasma renin and aldosterone were decreased in SS compared with SR, and C. No differences in plasma catecholamines or their changes with intake sodium modifications were seen among the patients. During high sodium intake urinary NO excretion increased in SR (38 +/- 9 vs 18 +/- 2 mg/g creat), and C (24 +/- 2 vs 16 +/- 3 mg/g creat) (p < 0.01) but not in SS patients (21 +/- 3 vs 26 +/- 4 mg/g creat). The NO excretion changes showed negative correlation with BP changes (r = 0.49, p < 0.01). During low sodium intake, SR and SS patients showed a normal nocturnal decrease of BP (dippers). During high sodium intake SS patients became non-dippers. Our results showed that patients with salt sensitive hypertension displayed a suppressed renin-aldosterone system, an attenuated nocturnal decline in blood pressure on high-salt diet and an impairment of endothelial function. The relationship between urinary nitrate excretion and arterial pressure suggest that the salt sensitivity of arterial pressure may be related bo blunted generation of endogenous nitric oxide.

Perfil hormonal y participación del óxido nítrico en la hipertensión arterial esencial 'sal sensible' y 'sal resistente' / Hormonal profile and role of nitric oxide in salt-sensitive and salt-resistant essential hypertension

Se desconoce la causa de la sensibilidad a la sal en la hipertensión arterial esencial (HTA). Dada la importancia del óxido nítrico (ON) en el manejo renal de Na+, es posible que existan diferencias en la generación de ON entre enfermos con HTA sensible a la sal (SS) e HTA resistente a la sal (SR). En el presente trabajo estudiamos el perfil hormonal y la participación del ON en 25 enfermos con HTA esencial que fueron clasificados como SS o SR por los cambios de la presión arterial media (PAM) de 24 horas, registrada por Spacelabs, en una dieta de 20 mEq/d de Na+ durante 5 días (fase hiposódica) y una dieta de 200 mEq/d de Na+ (fase hipersódica).En 13 enfermos la variación de la PAM fue _ 10 mmHg (SS). En todos los grupos hubo gran adherencia a la dieta demostrada por la natriuresis e ingesta proteica. No existieron diferencias en el filtrado glomerular (FG) entre los grupos con HTA. Los niveles de uricemia, triglicéridos e inhibidor del activador del plasminógeno (PAI-I) fueron mayores en el grupo SS que en SR y en controles sanos (C). Los niveles de actividad renina y aldosterona en la fase hiposódica fueron significativamente inferiores en los enfermos SS que en SR y en C. La variación porcentual de estas hormonas a la ingesta de sal fue inferior en los enfermos con HTA SS. No se observaron diferencias significativas en los valores de catecolaminas ni en las variaciones de éstas a los cambios de la ingesta de sal entre los diferentes grupos. Todos los enfermos presentaron, en la fase hiposódica, un descenso normal de la PAM nocturna. En la fase hipersódica, sin embargo, el descenso fue significativamente inferior en el grupo SS. Tras la sobrecarga de sodio se observó un aumento significativo de la excreción urinaria de metabolitos de ON, nitratos y nitritos (NOx), en C (24 ñ 2 vs 16 ñ 3), y en SR (38 ñ 9 vs 18 ñ 2 mglg creat.). Los NOx no se modificaron en los enfermos SS. Se objetivó una correlación inversa entre ANOx y APAM (r: -0,50, p < 0,01). El análisis de regresión logística reveló que la falta de incremento de la excreción de NOx era un factor de riesgo para la sensibilidad a la sal. Nuestros resultados demuestran que en los enfermos con HTA SS, comparados con los SR, hay una mayor supresión del sistema resina-aldosterona que es menos modificable con los cambios de ingesta de sal, y una pérdida del ritmo circadiano de la PA inducida por alta ingesta de NA+. Las alteraciones encontradas en el comportamiento de los metabolitos del ON y sus relaciones con la PA suscitan la importancia de aquel en la génesis de la sensibilidad a la sal (AU)

[L-arginine-nitric oxide pathway in hemodialysis]. / Vía de L-arginina-óxido nítrico en la hemodiálisis.

Nitric oxide (NO) is derived from the metabolism of the amino acid L-arginine by NO synthase (NOS). One of the forms of NOS (i-NOS) can be induced by cytokines, bradykinin and endotoxin. During hemodialysis (HD), blood-dialysis membrane interaction can induce production of these mediators. HD can also induce changes of asymmetrical dimethylarginine (ADA), a potent inhibitor of NOS. The aim of this study was to investigate the effect of HD, using cuprophane (C, polyacrilonytrile (PAN) and special polyacrylonitrile (SPAN) membranes, on cellular NOS activity, and changes of plasma tumor necrosis factor (TNF-alpha), bradykinin, ADA and nitrate concentration. Before HD, cellular i-NOS activity was similar with the three membranes. Cuprophane HD induced a significant increase in i-NOS activity from 31 +/- 10 to 48 +/- 12 fmol-1 10(6) cells (p < 0.05). No changes were found in PAN and SPAN HD. The TNF-alpha values increased significantly during HD with C (56 +/- 6 vs 47 +/- 5 pg/ml, p < 0.05). No changes of bradykinin concentration were found during HD. A significant decrease of ADA and nitrate levels was observed during HD with three membranes. No significant correlation was found between percentage increase in i-NOS activity and the changes in other parameters. These findings suggest that HD with bioincompatible membranes can induce activation of cellular i-NOS.

Vía de L-arginina-óxido nítrico en la hemodiálisis / L-arginine-no pathway in hemodialysis

El óxido nítrico (ON) deriva de la acción de la óxido nítrico sintasa (ONS). Una de las isoformas de esta enzima, la ONS tipo II puede ser inducida (ONS-i) por diversos estímulos como citoquinas, endotoxinas y bradiquinina entre otros. Durante la Hemodiálisis (HD) pueden generarse, dependiendo de las características de la membrana, estos mediadores. La HD puede también inducir cambios en la concentración de sustancias con capacidad de inhibir la ONS como dimetil-L-arginina asimétrica (DAA).En el presente trabajo se analizan los efectos de la HD con membranas de diferente biocompatibilidad cuprofán (C), poliacrilonitrilo (PAN) y poliacrilonitrilo especial (SPAN) en la actividad celular de la ONS-i, en los niveles de activadores de la ONS como factor de necrosis tumoral (TNF-a) y bradiquinina, y de inhibidores de la ONS como la DAA, y los cambios de nitratos, marcadores de la generación de ON. La actividad de la ONS-i celular pre-HD fue similar en todas las membranas. Tras la HD se evidenció un aumento significativo de la actividad ONS-i en la membrana de C (31 ñ 10 frente a 48 ñ 23 fmol -1.106 células, p < 0,05) mientras que no se modificó en las membranas de PAN y SPAN (31 ñ 9 frente a 31 ñ 6 y 44 ñ 14 frente a 34 ñ 11 fmol-1.106 células, respectivamente). En la HD con C se observó un aumento significativo de TNFa. Esta monoquina descendió tras la HD con PAN y no se modificó en la HD con SPAN. Con ninguna de las membranas se observaron modificaciones significativas de la bradiquinina. Con los tres procedimientos se observó un descenso significativo de los niveles de DAA y nitratos en el transcurso de la HD. No se observó correlación significativa entre las modificaciones de la actividad de la ONS-i celular y las variaciones de TNFalfa, bradiquinina, DAA, nitratos ni los valores de la presión arterial. Estos resultados evidencian que durante l a HD puede producirse un aumento de la actividad de la ONS-i celular por mecanismos relacionados con la biocompatibilidad de la membrana de diálisis. Por otra parte, la determinación de nitratos no es útil como marcador de la generación de ON durante la HD debido a sus pérdidas transdialíticas (AU)

Free protein S deficiency in hemodialysis patients due to vascular calcifications?

Vascular calcifications are frequent in hemodialysis patients. Its incidence ranges from 25 to 67% depending of different series. Thirty hemodialysis patients were selected from a dialysis population of 150 patients. These 30 patients were divided into two groups: group I included 15 hemodialysis patients with severe secondary hyperparathyroidism and severe, roentgenographically visible diffuse vascular calcifications, and group II included 15 other hemodialysis patients with moderate hyperparathyroidism without radiographic evidence of arterial calcifications. The control group comprised 20 normal volunteers. In all patients, measurements of protein C activity, free protein S and intact parathyroid hormone (PTH) were performed. Statistical analysis showed that free protein S in the patients of group I had a tendency to be lower than in the patients of group II (p < 0.01) and the control group (p < 0.001). We did not find significant differences in free protein S between group II and control group patients nor a significant correlation between intact PTH and free protein S in groups I and II. Protein C activity was found to be in the normal range in both groups. Free protein S deficiency in patients of group I would suggest a synthesis defect by impaired endothelial cells-due to vascular calcifications (?). Free protein S deficiency could increase the risk of thrombotic complications in these patients.

Treatment of severe secondary hyperparathyroidism with administration of calcium carbonate, intermittent high oral doses of 1,25-dihydroxyvitamin D3 and dialysate with 3 mEq/1 calcium concentration.

In this study, we evaluated the effect of long-term administration of daily calcium carbonate (2-4 g/day) and intermittent high oral doses of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3, 3-4 micrograms, given twice a week] in conjunction with a 3-mEq/1 calcium concentration in the dialysate for the treatment of severe secondary hyperparathyroidism in 6 hemodialysis patients. All patients had reduced serum levels of 1,25-(OH)2D3, which increased significantly (p < 0.005) reaching the maximum level in the 4th month. Serum total and ionized calcium levels significantly increased also, in relation to those before treatment. No patients developed hypercalcemia. Serum phosphorus did not significantly change during the study. Initial serum intact parathyroid hormone (PTH) (1,241 +/- 233 pg/ml, mean +/- SEM) markedly decreased after starting treatment with 1,25-(OH)2D3, being 542 +/- 174 pg/ml in the 5th month and 477 +/- 174 pg/ml in the 8th month. These changes are statistically significant (p < 0.05 and < 0.007, respectively). Alkaline phosphatase behavior was similar to that of intact PTH. A constant direct correlation between intact PTH and alkaline phosphatase and an inverse significant correlation between intact PTH and 1,25-(OH)2D3 was evidenced by us. We conclude that oral 1,25-(OH)2D3 pulse therapy is very effective in suppressing PTH secretion. The administration of calcium carbonate and the use of dialysate with a reduced calcium concentration would allow to prevent hyperphosphatemia and the administration of high oral doses of 1,25-(OH)2D3 without concomitant hypercalcemia.

[Chronic kidney insufficiency and respiratory muscle function. Changes induced by treatment with 1,25(OH)2D3]. / Insuficiencia renal crónica y función muscular respiratoria. Modificaciones inducidas por el tratamiento con 1,25 (OH)2D3.

A myopathy basically involving proximal respiratory muscles can develop in uremia. To evaluate respiratory muscle force in uremia, maximal inspiratory pressure (MIP) was measured in 27 patients with renal failure. MIP was very limited in patients with a creatinine clearance (Crc) lower than 10/ml/min 1.73 m2 not treated with hemodialysis (HD) and in patients on HD who were not treated with 1.25 (OH)2D3 (45 +/- 9 and 43 +/- 5 cm H2O, respectively), moderately reduced in patients on HD treated with 1.25 (OH)2D3 (58 +/- 5 cmH2O) and normal in patients with Crc higher than 10 ml/min 1.73 m2 (86 +/- 6 cmH2O). The treatment with 1.25 (OH)2D3 during 3 months promoted a significant increase in MIP and serum calcium level and a reduction in parathyroid hormone in patients with Crc lower than 10 ml/min. It was concluded that, in uremia, a respiratory muscle weakness partially reversible with vitamin D therapy may be found.

[Autonomic function in uremia and diabetes mellitus]. / Función autonómica en la uremia y en la diabetes.

Autonomic function was evaluated in three groups of patients: diabetics, nondiabetic uremics, and uremic nondiabetics. Autonomic function was assessed with a parasympathetic function test (Valsalva maneuver) and two sympathetic function tests (cold and amyl nitrite). The results showed that all groups of patients, as compared with healthy controls, had a dysfunction of the autonomic nervous system (ANS). This ANS involvement, both in the parasympathetic and the sympathetic divisions, was much more severe in those patients with simultaneous uremia and diabetes.

[Degradation of purine nucleotides in patients with chronic obstruction to airflow]. / Degradación de los nucleótidos purínicos en pacientes con obstrucción crónica al flujo aéreo.

The increase in hypoxanthine (Hx), xanthine (X), uric acid (VA) and total purines (TP) that may be found in several clinical conditions associated with tissue hypoxia has been attributed to an increase in adenine nucleotides degradation by a reduced ATP synthesis caused by oxygen deprivation. To test this hypothesis we have investigated the urinary excretion of Hx, X, VA, TP and radioactivity elimination after labeling the adenine nucleotides with adenine (8-14C) in 5 patients with chronic airflow obstruction (CAFO), in the basal state and after oxygen therapy (FiO2, 24%). The results were compared with those from 4 normal individuals. Patients with COFA showed an increase of the renal elimination of Hx, X, VA, TP and radioactivity, which was significantly different from the control group (p less than 0.05). Oxygen administration was associated with a significant reduction in the excretion of purines and radioactivity (p less than 0.01), which decreased to values similar to those found in normal individuals. These findings suggest that in patients with COFA and severe hypoxemia there is a marked increase in the degradation of adenine nucleotides. The normalization of the purine and radioactivity excretion after oxygen therapy points to a basic role of oxygen in the catabolism of adenine nucleotides.