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.

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.

[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.

[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.

[Rapidly progressive glomerular disease treated with plasmapheresis (author's transl)]. / Glomerulonefritis rápidamente progresiva tratada con plasmaféresis.

A case of rapidly progressive glomerular disease with 100% of epithelial crescents completely enveloping each glomerulus, prolonged anuria and renal failure requiring dialysis. There were no indications of either streptococcal etiology or systemic disease. Improvement in renal function in response to plasmapheresis and immunosuppressants was spectacular. During two subsequent episodes of renal failure with diminished diuresis response to plasmapheresis was again striking. Assay for circulating immune-complex was always negative. No anti-basement membrane antibodies were found. Due to the lack of an adequate vascular access plasmapheresis was discontinued and the patient died 7 months after onset. Tendency to interstitial glomerular sclerosis was established with three renal biopsy specimens taken during progression of the disease. Intense metabolic acidosis suggestive of tubular acidosis, disproportionate to renal insufficiency presented during the last months. Pathologic and prognostic aspects as well as possible access for plasmapheresis are discussed.

Drug intoxication and neurological episodes in chronic renal failure.

Of 178 episodes of neurological derangement in 103 patients with renal failure, only about 40% were due to known causes such as hypertension or electrolyte failure. One-third were due to drug intoxication and no definite aetiology was found for the remainder. Drug intoxication is due partly to the accumulation of a drug normally excreted by the kidney and partly to a greater susceptibility of the central nervous system in uraemic patients. The prognosis is favourable.

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.

[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.

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.