A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients.

Prehemodialysis and hemodialysis patients are at an increased risk of hepatitis B infection and have an impaired immune response to hepatitis B vaccines. We evaluated the immune response to the new adjuvant of hepatitis B vaccine AS04 (HBV-AS04) in this population. We measured antibody persistence for up to 42 months, and the anamnestic response and safety of booster doses in patients who were no longer seroprotected. The primary vaccination study showed that HBV-AS04 elicited an earlier antibody response and higher antibody titers than four double doses of standard hepatitis B vaccine. Seroprotection rates were significantly higher in HBV-AS04 recipients throughout the study. The decline in seroprotection over time was significantly less in the HBV-AS04 group with significantly fewer primed patients requiring a booster dose over the follow-up period. Solicited/unsolicited adverse events were rare following booster administration. Fifty-seven patients experienced a serious adverse event during the follow-up; none of which was vaccine related. When HBV-AS04 was used as the priming immunogen, the need for a booster dose occurred at a longer time compared to double doses of standard hepatitis B vaccine. Hence, in this population, the HBV-AS04 was immunogenic, safe, and well-tolerated both as a booster dose after HBV-AS04 or standard hepatitis B vaccine priming.

[Survival of myeloma patients treated with dialysis]. / Supervivencia de pacientes con mieloma tratados con diálisis.

BACKGROUND: Renal failure is a common complication of myeloma. Renal replacement therapy in these patients is controversial due to poor survival outcomes and low tolerance to treatment. We reviewed our experience on patients with myeloma undergoing dialysis therapy at one centre. PATIENTS AND METHODS: Between 1980 and 2000, 28 patients (21 men and 7 women) with myeloma were admitted to chronic dialysis programme and the following variables were analysed: sex, age when starting dialysis, lapse of time between diagnosis of myeloma and admission to dialysis (TD), disease stage, comorbity, mode of presentation, calcium, creatinine at diagnostic, albumin and Hb at the beginning of dialysis, and cause of death. We studied survival among these patients (Kaplan-Meier), identified predictors of survival outcome (Cox's regression) and compared survival between the two decades studied. RESULTS: Mean age was 65 years, median TD was 0.4 months, and modes of presentation were: end-stage renal failure (18 patients), acute renal failure (8), amyloldosis (2). Eleven patients (39%) had myeloma IgG, four (14%) IgA and thirteen (46%) had light chains. Kappa light chain was the most frequent one. In 75% of patients myeloma was at IIIb stage. Cause of death were: Cardiovascular disease (5 patients), infections (4), suspension of treatment (4), tumours (4), and others causes (2). Median survival for all patients was 16.8 months (range 0.4-78) and 25% survived over 39 months. Hb level was the only significant predictor in the multivariant analysis (p = 0.02). In the 80's median survival was 6.17 months versus 17 months in the 90's but this difference was not significant with long-rank test. CONCLUSION: Although survival of patients with myeloma treated with dialysis is still short, 25 percent survive over 3 years, being Hb level the only predictive factor. Moreover, we observed an improvement of survival in recent years.

[Multicenter study of darbepoetin alfa in the treatment of anemia secondary to chronic renal insufficiency on dialysis]. / Estudio multicéntrico de darbepoetin alfa en el tratamiento de la anemia secundaria a insuficiencia renal crónica en diálisis.

This Spanish single-arm, multicenter, prospective clinical trial assessed the maintenance of hemoglobin concentrations (Hb) between 10-13 g/dL with unit doses of darbepoetin alfa and the safety of the treatment in dialysis patients. Eight-hundred twenty-six patients with chronic renal failure (CRF) (94% receiving haemodialysis and 6% receiving peritoneal dialysis) previously maintained on stable recombinant human erythropoietin (r-HuEPO) therapy with stable hemoglobin (Hb) concentrations (mean Hb concentration = 11.7 g/dL) were switched to darbepoetin alfa at a reduced dosing frequency for 24 weeks (a 20-week titration phase plus a 4-week treatment evaluation phase). Subjects receiving r-HuEPO two or three times weekly were switched to darbepoetin alfa once weekly, and those. who were receiving r-HuEPO once weekly were switched to darbepoetin alfa once every two weeks. The initial dose of darbepoetin alfa was determined from the r-HuEPO dose at inclusion into the study using a formula equating the peptide mass of the two molecules and rounding to the nearest available prefilled syringe dose. Overall, 86.8% of patients completed the 24-weeks of study. Changing the treatment from r-HuEPO to darbepoetin alfa and increasing the dose interval did not result in any clinically significant change in the Hb concentration. From base-line to the evaluation phase, the mean Hb fell 0.09 (95% CI, -0.2; -0.0) g/dl, with an increase of 0.19 (95% CI, 0.0;0.3) g/dL i.v. and a decrease of 0.22 (95% CI, -0.3; -0.1) g/dL s.c.). This maintenance of the mean Hb concentration was accompanied by a mean 9.8% reduction of the darbepoetin alfa dose (19.7% (95% CI, -24.9; -14.2) i.v. and 4.7% (95% CI, -8.5; -0.7) s.c. Treatment with darbepoetin alfa was well tolerated and no unexpected adverse events were reported. In conclusion, the replacement of previous r-HuEPO treatment by darbepoetin alfa in the therapy of anemia secondary to chronic renal failure in diaiyzed patients was effective, well tolerated, and decreased the frequency of dose administration compared with the previous r-HuEPO treatment. Darbepoetin alfa administered once weekly or once every two weeks maintained the baseline Hb levels whilst allowing dose reduction, which was higher in patients receiving i.v. darbepoetin alfa.

Estudio multicéntrico de darbepoetin alfa en el tratamiento de la anemia secundaria a insuficiencia renal crónica en diálisis / Darbepoietin treatment of anemia secondary to chronic renal failure in dialysis

Este ensayo clínico prospectivo, multicéntrico, de un solo brazo, evaluó el mantenimiento de las concentraciones de hemoglobina (Hb) entre 10-13 g/dL con darbepoetin alfa y la seguridad de este tratamiento, en pacientes con insuficiencia renal crónica (IRC) en diálisis (94% hemodiálisis, 6% diálisis peritoneal, concentración de Hb basal = 11,7 g/dL) tratados hasta el inicio de este estudio con eritropoyetina recombinante humana (r-HuEPO). Se incluyeron 826 pacientes con concentraciones de Hb y dosis de r-HuEPO estables (824 recibieron al menos una dosis de darbepoetin alfa y fueron evaluables para el análisis de seguridad). Los pacientes recibieron darbepoetin alfa durante 24 semanas (20 de titulación más 4 de evaluación). La dosis inicial de darbepoetin alfa se determinó a partir de la dosis previa de r-HuEPO, utilizando la equivalencia en masa peptídica entre ambas moléculas y ajustando a la jeringa precargada más próxima. Se administró darbepoetin alfa 1 × semana (en pacientes en tratamiento previo con r-HuEPO 2-3 × semana) o cada dos semanas (en los pacientes con r-HuEPO 1 × semana). El 86,8% de los pacientes completaron las 24 semanas de estudio. El cambio del tratamiento a menor frecuencia de dosificación no produjo modificaciones clínicamente significativas en la concentración de Hb [los cambios desde la visita basal al período de evaluación consistieron en un descenso de 0,09 (IC 95%, –0,2; –0,0) g/dL, con aumento de 0,19 (IC 95% 0,0; 0,3) g/dL en la vía iv y descenso de 0,22 (IC 95%, –0,3; –0,1) g/dL en la vía sc]. Este mantenimiento de Hb se acompañó de una reducción media de la dosis de darbepoetin alfa de un 9,8% (IC 95%, –12,9; –6,6) [19,7% (IC 95%, -24,9;-14,2) (vía iv) y 4,7% (IC 95%, –8,5; –0,7) (vía sc)]. El tratamiento con darbepoetin alfa fue bien tolerado, no observándose acontecimientos adversos inesperados. En conclusión, la sustitución de cér-HuEPO por darbepoetin alfa en la terapia de la anemia secundaria a IRC en pacientes en diálisis fue eficaz, bien tolerada y disminuyó la frecuencia de administración de dosis en comparación con el tratamiento previo con r-HuEPO. Darbepoetin alfa 1 vez por semana o 1 vez cada 2 semanas mantuvo los niveles de Hb basales a la vez que permitió una reducción de la dosis por ambas vías de administración, siendo mayor en los pacientes tratados por vía iv

This Spanish single-arm, multicenter, prospective clinical trial assessed the maintenance of hemoglobin concentrations (Hb) between 10-13 g/dL with unit doses of darbepoetin alfa and the safety of the treatment in dialysis patients. Eight-hundred twenty-six patients with chronic renal failure (CRF) (94% receiving haemodialysis and 6% receiving peritoneal dialysis) previously maintained on stable recombinant human erythropoietin (r-HuEPO) therapy with stable hemoglobin (Hb) concentrations (mean Hb concentration = 11.7 g/dL) were switched to darbepoetin alfa at a reduced dosing frequency for 24 weeks (a 20-week titration phase plus a 4-week treatment evaluation phase). Subjects receiving r-HuEPO two or three times weekly were switched to darbepoetin alfa once weekly, and those. who were receiving r-HuEPO once weekly were switched to darbepoetin alfa once every two weeks. The initial dose of darbepoetin alfa was determined from the r-HuEPO dose at inclusion into the study using a formula equating the peptide mass of the two molecules and rounding to the nearest available prefilled syringe dose. Overall, 86.8% of patients completed the 24-weeks of study. Changing the treatment from r-HuEPO to darbepoetin alfa and increasing the dose interval did not result in any clinically significant change in the Hb concentration. From baseline to the evaluation phase, the mean Hb fell 0.09 (95% CI, –0.2; –0.0) g/dl, with an increase of 0.19 (95% CI, 0.0;0.3) g/dL iv and a decrease of 0.22 (95% CI, –0.3; –0.1) g/dL sc). This maintenance of the mean Hb concentration was accompanied by a mean 9.8% reduction of the darbepoetin alfa dose (19.7% (95% CI, –24.9;-14.2) iv and 4.7% (95% CI, –8.5; –0.7) sc. Treatment with darbepoetin alfa was well tolerated and no unexpected adverse events were reported. In conclusion, the replacement of previous r-HuEPO treatment by darbepoetin alfa in the therapy of anemia secondary to chronic renal failure in diaiyzed patients was effective, well tolerated, and decreased the frequency of dose administration compared with the previous r-HuEPO treatment. Darbepoetin alfa administered once weekly or once every two weeks maintained the baseline Hb levels whilst allowing dose reduction, which was higher in patients receiving iv darbepoetin alfa

Supervivencia de pacientes con mieloma tratados con diálisis / Survival in patients with myeloma treated with dialysis

Introducción: La insuficiencia renal es una complicación frecuente del mieloma (MM). La indicación de tratamiento sustitutivo de la función renal en estos pacientes es controvertida, debido a mala supervivencia y tolerancia. Se revisa la experiencia de nuestro centro con todos los pacientes diagnosticados de MM durante los últimos 20 años y admitidos a programa de diálisis crónica. Pacientes y métodos: Se estudian 28 pacientes (21 hombres y 7 mujeres) con MM y que iniciaron tratamiento con diálisis entre los años 1980 y 2000 en los que se evaluaron variables clínicas y analíticas: sexo, edad al inicio de diálisis, tiempo entre el diagnóstico y la entrada en diálisis (TD), estadio de la enfermedad, presencia de comorbilidad, forma de presentación, calcio sérico, creatinina en el momento del diagnóstico, albúmina, hemoglobina al inicio de la diálisis (Hb) y causa de muerte. Se estudia también la supervivencia (método de Kaplan-Meier) y se trató de identificar variables predictoras con el análisis de regresión de Cox. Para valorar la respuesta al tratamiento se dividieron los casos aparecidos en dos períodos de diez años. Resultados: Con una edad media de 65 años, la mediana para el intervalo diagnóstico inicio diálisis (TD) fue de 0,4 meses. En 18 casos la afectación renal se presentó como insuficiencia renal crónica, fracaso renal agudo en 8 y amiloidosis en 2. Once pacientes (39%) fueron MM IgG, 4 (14%) IgA, y 13 (46%) con cadenas ligeras. El 75% presentaban un estadio IIIb. Las causas de muerte fueron: cardiovasculares en 5 casos, infecciones en 4, cese del tratamiento en 4, tumoral en 4 y otras en 2. La mediana de la supervivencia fue de 16,8 meses para todo el grupo (rango 0,4-78), y en el análisis multivariante sólo las concentraciones de hemoglobina resultaron predictivas (p = 0,02). El 25% de los pacientes sobrevivió 39 meses. En la década de los ochenta la mediana fue de 6,17 meses y para los noventa de 17 meses. Esta diferencia no alcanzó significación estadística con el log-rank test (p = 0,12). Conclusión: Aunque la supervivencia de los pacientes con MM en diálisis sigue siendo baja, una proporción estimable sobrevive más de tres años y además se evidencia una tendencia hacia una mayor supervivencia en la última década. La Hb fue la única variable predictora encontrada

Background: Renal failure is a common complication of myeloma. Renal replacement therapy in these patients is controversial due to poor survival outcomes and low tolerance to treatment. We reviewed our experience on patients with myeloma undergoing dialysis therapy at one centre. Patients and methods: Between 1980 and 2000, 28 patients (21 men and 7 women) with myeloma were admitted to chronic dialysis programme and the following variables were analysed: sex, age when starting dialysis, lapse of time between diagnosis of myeloma and admission to dialysis (TD), disease stage, comorbidity, mode of presentation, calcium, creatinine at diagnostic, albumin and Hb at the beginning of dialysis, and cause of death. We studied survival among these patients (Kaplan-Meier), identified predictors of survival outcome (Cox’s regression) and compared survival between the two decades studied. Results: Mean age was 65 years, median TD was 0.4 months, and modes of presentation were: end-stage renal failure (18 patients), acute renal failure (8), amyloldosis (2). Eleven patients (39%) had myeloma IgG, four (14%) lgA and thirteen (46%) had light chains. Kappa light chain was the most frequent one. In 75% of patients myeloma was at Illb stage. Cause of death were: Cardiovascular disease (5 patients), infections (4), suspension of treatment (4), tumours (4), and others causes (2). Median survival for all patients was 16.8 months (range 0.4-78) and 25% survived over 39 months. Hb level was the only significant predictor in the multivariant analysis (p = 0.02). In the 80’s median survival was 6.17 months versus 17 months in the 90's but this difference was not significant with long- rank test. Conclusion: Although survival of patients with myeloma treated with dialysis is still short, 25 percent survives over 3 years, being Hb level the only predictive factor. Moreover, we observed an improvement of survival in recent years

Tratamiento con hierro intravenoso e infección en hemodiálisis

No disponible

contribuciones y aplicaciones de la medida ambulatoria de la presión arterial en la hipertensa menopáusica / Ambulatory blood pressure monitoring contributions and applications in postmenopausal hypertensives

No disponible

[Study of various factors that could have an impact on the treatment with erythropoietin of hemodialysis anemia]. / Estudio de algunos factores que pueden influir en el tratamiento con eritropoyetina de la anemia en hemodiálisis.

Several factors influence the efficacy of the action of human recombinant erythropoietin during treatment of anaemia in haemodialysis patients. We carried out a six-month prospective study of 23 stable patients who had been on haemodialysis for at least one year to attempt to evaluate those factors modifying the dose of the hormone to attain a similar haematocrit, such as use or not of angiotensin converting enzyme inhibitors, hepatitis C virus positive or negative, age older or younger than 60 years, acquired cystic kidney disease or not, and sex. The patients were treated with subcutaneaous erythropoietin for over a year to attain a haematocrit of 35%, intravenous iron to reach plasma ferritin levels > 250 ng/ml and a transferrin saturation index > 20%, folic acid and group B vitamins. Parameters studied included age, time and duration of haemodialysis, Kt/V, albumin, haematocrit, erythropoietin in U/kg/week, intact PTH, hepatitis C virus, PCR of the hepatitis C virus, transaminases, ferritin, transferrin saturation index, folic acid, vitamin B12, and aluminium. No statistically significant differences were seen between the patients with and without hepatitis or in age or acquired cystic kidney disease and sex in the hormone dose given to achieve similar levels of haematocrit. Higher doses of erythropoietin were necessary in those patients treated with antihypertensive agents (71 +/- 25 vs 44 +/- 25 U/kg/week; p < 0.05). There were no differences between groups in factors known to cause resistance to the action of the hormone. The most important conclusions from this study concern the cost-benefit relation of treating hypertensive patients on haemodialysis with angiotensin converting enzyme inhibitors and erythropoietin.

Hipertensión e hipercolesterolemia en la población española

No disponible

Estudio de algunos factores que pueden influir en el tratamiento con eritropoyetina de la anemia en hemodiálisis / Study of several factors influencing the treatment of dialysis-associated anaemia with erythropoietin

La eficacia de la acción de la eritropoyetina humana recombinante en el tratamiento de la anemia de los pacientes en diálisis está limitada por algunos factores. Presentamos un estudio prospectivo de 6 meses de duración en 23 pacientes estables, tratados en hemodiálisis más de un año, valorando si determinados parámetros modificaban la dosis de la hormona para obtener un hematocrito similar. Se estudió: tratamiento o no con inhibidores de la enzima conversora de la angiotensina II, diagnóstico o no de hepatopatía virus C, o enfermedad renal quística adquirida, edad mayor o menor de 60 años y sexo. Los pacientes estaban tratados con eritropoyetina vía subcutánea, durante más de un año, para alcanzar un hematocrito de 35 por ciento; con hierro vía intravenosa para conseguir niveles de ferritina plasmática mayores de 250 ng/ml y un índice de saturación de transferrina mayor del 20 por ciento, ácido fólico y vitaminas del grupo B. Parámetros estudiados: edad, tiempo y duración de la diálisis, KTV, albúmina, hematocrito, eritropoyetina en u/kg/semana, PTH intacta, virus C, PCR del virus C, transaminasas, ferritina, índice de saturación de transferrina, a. fólico, vit B12 y aluminio plasmático. Los pacientes tratados con el antihipertensivo precisan dosis mayores de hormona que los no tratados (71 ñ 25 vs 44 ñ 25 u/kg/semana, p < 0,05); en los restantes grupos estudiados no observamos diferencia estadística significativa en los requerimientos de eritropoyetina para conseguir un hematocrito semejante. La comparación de los valores de otros factores conocidos de resistencia a la acción hormonal fue similar en los distintos grupos. El único factor que limita la eficacia de eritropoyetina es el tratamiento con los antihipertensivos por lo que es importante señalar que debe tenerse en cuenta la relación coste-beneficio de pacientes en hemodiálisis hipertensos y anémicos a los que se prescribe inhibidores de la enzima conversora de la angiotensina (AU)

[Long-term effects of captopril versus nifedipine retard on the lipid profile of mild to moderate normolipidemic essential hypertension patients. In representation of the Eastern Andalouz Cooperative Study]. / Efectos a largo plazo de captopril frente a nifedipino retard sobre el perfil lipídico de hipertensos esenciales ligero-moderados normolipidémicos. En representación del Grupo Colaborativo Andaluz Oriental.

The aim of the study was to evaluate the long-term (12 months) effects of captopril and nifedipine retard on the lipid profile of the non obese, non diabetic and normolipemic essential hypertensives. In a multicenter, randomised, open study we included 185 mild-moderate essential hypertensives responders to captopril (n = 96) or nifedipine retard (n = 89) in monotherapy, and with a total cholesterol between 200-239 mg/dl. No dietetic recommendations were given to the patients, except for moderate salt restriction. After 1 year follow-up, our results show that both drugs improved the lipid profile of the hypertensives. Patients with nifedipine retard showed a statistical significant decrease in the level of the total and LDL cholesterol and apoprotein B; while total and LDL cholesterol, triglycerides and apoproteins significantly decreased in the group treated with captopril. The possible pharmacological mechanisms involved in these beneficial effects are discussed; concluding that these properties made much more attractive these drugs to be used as first step therapy in the essential hypertensives.

Nitrendipine in the therapeutic management of elderly hypertensive patients: results of a multicenter trial. Andalousian Hypertension Group.

Two hundred forty-seven [142 women (57.49%)] elderly patients with essential hypertension (diastolic blood pressure between 95 and 114 mm Hg) and an average age of 67.4 +/- 6 years were included in an open multicenter ambulatory trial. One hundred thirty-seven had some kind of associated disease. After a 15-day washout period, the patients began nitrendipine therapy (10 mg o.d.). After 1 month, the dose was increased to 20 mg o.d. in patients with diastolic blood pressure (DPB) greater than or equal to 95 mm Hg, and thereafter 5 and 10 mg o.d. of bisoprolol was added to the maximal dose of nitrendipine (20 mg o.d.) in the case of patients with DBP greater than or equal to 95 mm Hg at the end of the second and third months, respectively. At the end of the 6-month follow-up period, the systolic and diastolic pressures had dropped -35 and -21 mm Hg, respectively, without any change in heart rate or Quetelet index. In 210 patients (84.9%), blood pressure control was achieved: 26 (10.5%) with 10 mg of nitrendipine, 149 (60.3%) with 20 mg of nitrendipine, and 35 (14.1%) by adding bisoprolol. The lipid profile, glucose, potassium, uric acid, or creatinine did not change negatively. Sixty-six (26.72%) patients reported clinical side effects, although these were mild; only 15 (6.07%) patients were excluded because of side effects. Nitrendipine has been shown to have a high therapeutic efficacy and biochemical tolerance for first-line treatment of elderly patients with mild-to-moderate essential hypertension with or without associated diseases.

Effects of dipyridamole on the short-term evolution of glomerulonephritis.

The aim of the present study is to evaluate the effect of dipyridamole (300 mg/day) versus placebo in a double-blind randomized trial on membranous glomerulonephritis (M-GMN), mesangial IgA glomerulonephritis (IgA-GMN), and segmentary and focal hyalinosis glomerulonephritis (SFH-GMN) during the first 3 months of treatment. In the case of M-GMN, proteinuria dropped by 60% of the basal value in patients treated with dipyridamole; in the case of IgA-GMN it dropped by 65-70%; and in the case of SFH-GMN it dropped by 40% of the basal value. Inhibition of proteinuria in M-GMN was correlated to platelet response, and above all, to the ADP-induced platelet aggregation in whole blood.

Diuretics and the treatment of systemic hypertension.

Diuretics are still among the most frequently used antihypertensive drugs in the treatment of hypertension. Their pharmacologic and hemodynamic properties are based on the water and salt metabolism in the pathophysiology of high blood pressure. Initially, there is a reduction of plasma and extracellular fluid volume; cardiac output also decreases. After this early phase, cardiac output returns to normal with an accompanying decrease in peripheral resistance so as to correct the underlying hemodynamic fault of the hypertensive state. Diuretics have a high therapeutic efficacy either as monotherapy or in combination with beta blockers, angiotensin-converting enzyme inhibitors or calcium antagonists. The main problem with the use of diuretics is related to their metabolic side effects, which are dose-related. Currently, there is a tendency to administer low-dose diuretics, which result in fewer clinical and metabolic side effects, but with a continued antihypertensive efficacy. Therefore, low doses of diuretics can be recommended as initial therapy in the stepped-care approach of hypertension.