C.E.R.A. safety profile: a pooled analysis in patients with chronic kidney disease.

BACKGROUND: C.E.R.A., a continuous erythropoietin receptor activator, is a long-acting erythropoiesis-stimulating agent (ESA) that is approved for the treatment of renal anemia. This analysis evaluated the safety profile of C.E.R.A. in comparison to that of other ESAs in patients with chronic kidney disease (CKD). METHODS: Safety parameters were analyzed in a pooled population comprising all patients with CKD on dialysis and not on dialysis from the completed Phase II and Phase III studies in the C.E.R.A. clinical program (Phase II/III population); patients were treated with either C.E.R.A. (n = 1,789) or comparator ESA (n = 948). Differences between treatment groups in safety parameters were identified by either a 2% difference in incidence between groups, or a statistically significant difference between groups (p < or = 0.05 with the Fisher's exact test, which was used as a conservative screening tool). To assess changes in safety findings over time, long-term safety data were analyzed from patients who were given the option to enter long-term safety studies upon completing their initial Phase II/III study (safety extension population). RESULTS: Compared with the C.E.R.A. group, the incidence of adverse events (AEs) was higher in the comparator ESA group in the Phase II/III population (C.E.R.A. vs. comparator ESA, 89.5% vs. 91.8%, p = 0.067), and significantly so in the safety extension population (93.0% vs. 95.8%, p = 0.003). The incidence of serious AEs was significantly higher in the comparator ESA group than in the C.E.R.A. group in both analysis populations (Phase II/III population, 37.8% vs. 42.4%, p = 0.021; safety extension population, 53.3% vs. 59.7%, p = 0.001). However, there was no consistent pattern of clinical events that could explain these differences between the treatment groups. CONCLUSION: Analysis of safety events in patients with renal anemia receiving long-term treatment with C.E.R.A. shows a safety profile comparable to that of other ESAs.

Therapy of intractable pruritus with MARS.

INTRODUCTION: Pruritus is the most disabling symptom in patients with cholestatic liver diseases. Many drug therapies have been used for the treatment of these diseases, with different outcomes. The molecular adsorbent recirculating system (MARS) has been used in the treatment of intractable pruritus in cholestatic syndromes. We report our experience with MARS in 3 patients with intractable pruritus on the waiting list: 2 liver transplant recipients and a patient with primary biliary cirrhosis. PATIENTS AND RESULTS: Two middle-aged women and 1 middle-aged man, who were recipients of an orthotopic liver transplant for primary biliary cirrhosis, underwent three (n = 2) and two (n = 1) 6-hour sessions of MARS due to medically uncontrollable pruritus. All noted marked improvement of pruritus, with decreased bilirubin levels, but this improvement lasted only a few days in all cases. We observed no changes in transaminase or albumin levels, or prothrombin time. Complications included an episode of angina due to anemia caused by jugular catheter bleeding, and thrombocytopenia in all patients. CONCLUSIONS: MARS is an effective treatment for intractable pruritus in cholestatic liver diseases, although its beneficial effect is short. This extracorporeal liver device is safe, because most related adverse events are mild.

The influence of hepatitis B and hepatitis C virus infection in the recipient on late renal allograft failure.

BACKGROUND: Chronic liver disease is one of the most important complications after renal transplantation. Hepatitis B and mainly hepatitis C are the more frequent causes of liver disease. Although there are controversial results, in some series, hepatitis B and hepatitis C are associated with lower graft and patient survival. PATIENTS AND METHODS: A total of 3365 adult patients who received a renal transplant in 1990 (N = 824), 1994 (N = 1075) and 1998 (N = 1466) with a functioning graft after the first year were included. Fifty-one (2.1%) with positive HbsAg were diagnosed with hepatitis B at transplantation; 488 (16.9%) presented positive anti-hepatitis C antibodies and were diagnosed with hepatitis C virus (HCV) infection and 25 patients (0.8%) were diagnosed with concomitant hepatitis B virus (HBV) and HVC infection. Demographic, immunosuppression, survival figures and post-transplant and follow-up data of these patients and negative HBV and HVC patients were recorded. RESULTS: The overall prevalence of HBV in the recipients was 2.1%. Patient survival was lower and liver disease was the main cause of death in HBV-positive patients. However, in the multivariate analysis the presence of positive HbsAg did not have an independent risk factor for graft loss and patient death. This finding was similar in patients with concomitant HBV and HVC infection. Graft and patient survival were lower in HCV-positive patients and liver disease was the main cause of death. Interestingly, proteinuria and serum creatinine were risk factors for graft loss and patient death. Fortunately, prevalence of HCV in the recipients significantly decreased from 29% in 1990 to 10% in 1998. CONCLUSIONS: In the last decade in Spain, HBV infection in the recipients, showing an overall prevalence approximately 2%, did not influence graft and patient survival. However, HCV infection in the recipient was associated with lower graft and patient survival, although the prevalence of HCV clearly decreased from 29% in 1990 to 10% in 1998.

[Differences in health-related quality of life between male and female hemodialysis patients]. / Diferencias en la calidad de vida relacionada con la salud entre hombres y mujeres en tratamiento en hemodíalisis.

BACKGROUND: Previous studies in renal patients have reported that women perceive a lower health-related quality of life (HRQOL) than men: however, these studies have been carried out without taking into account the gender-related differences shown in general population samples. The aims of the present study are: a) to define the HRQOL dimensions in which there are differences between men and women on chronic hemodialysis (HD), correcting then the differences on the generic dimensions by means of standardization by age and gender of the obtained scores, using Spanish normative data, and b) to identify the variables that cause these possible gender-related differences on HRQOL. METHODS: A cross-sectional multi-center study was carried out with 152 patients (69 men and 83 women) receiving HD treatment in 43 Spanish centers, using the KDQOL-SF to evaluate their HRQOL. The generic KDQOL-SF scores were standardized by age and gender using Spanish normative data. Sociodemographic, clinical and psychosocial variables were also collected on each patient. A MANOVA was carried out to study the variables associated with the gender-related differences on HRQOL. The sociodemographic, clinical and psychosocial variables showing significant differences between men and women in the previous univariate analysis were entered as covariates. RESULTS: The KDQOL-SF scores showed statistically significant differences between men and women in four scales: physical functioning, emotional role limitation, social function and emotional well-being. In contrast, standardized scores showed no differences between men and women in the profile or degree of HRQOL impairment. Although statistically significant gender-related differences were shown in educational level, employment, haemoglobin, Kt/V, trait anxiety and depressive symptoms, only the last two variables showed an independent effect on the differences in HRQOL. CONCLUSION: Impaired HRQOL in women on HD reflects the gender-related differences that are also shown in the general population, and they are related to the higher prevalence of trait anxiety and depressive symptoms in women.

Changes in quality of life after renal transplantation.

The objective of this study was to evaluate the modifications that renal transplantation produces on the quality of life (QOL) of patients with chronic renal failure (CRF) previously undergoing hemodialysis (HD) and to analyze the possible factors implicated. A multicenter study of QOL was performed on 1,023 patients undergoing dialysis, using as QOL indicators the Karnofsky Scale (KS) and the Sickness Impact Profile (SIP). Among this group, 93 patients received a renal transplant and QOL was re-studied in them; each subject, therefore, was his own control. In the 88 patients with a functioning graft, an improvement in QOL indices was globally observed; this improvement was much more marked in men than in women, for unclear reasons. Older age and greater prior comorbidity diminished the beneficial effects of transplantation.

[Randomized, comparative study to evaluate efficacy and safety of doxazosin versus nitrendipine in the treatment of mild to moderate hypertension]. / Estudio randomizado, comparativo, sobre la eficacia y seguridad de doxazosina frente a nitrendipino en el tratamiento de la hipertensión arterial ligera a moderada.

Doxazosin, an alfa-1 adrenoceptor antagonist, was compared with nitrendipine, a calcium antagonist, to evaluate their efficacy and safety in 61 patients with mild to moderate hypertension. 31 patients were assigned randomly to receive 1-16 mg of doxazosin and 30 patients were assigned to 10-20 mg of nitrendipine during 14 weeks (10 weeks of titration and 4 weeks of maintenance). Mean final dose was 6.1 mg for doxazosin and 15.6 mg for nitrendipine. Both treatments reduced supine and standing diastolic and systolic blood pressure (p < 0.01 for all comparisons). 22 patients in the doxazosin group (78.6%) and 18 in the nitrendipine group (78.3%) were considered therapy successes. There were not clinically significant changes in laboratory tests for both groups. Global assessment of adverse events was similar for both treatments (46.7% for doxazosin and 44.8% for nitrendipine), although patients treated with nitrendipine presented facial rush (20%) against none of the doxazosin group (p < 0.05). Withdrawals due to adverse events were higher in the nitrendipine group than in the doxazosin one (20.7% versus 6.7%, p = 0.14). The results of this study confirms that both antihypertensives reduced blood pressure in patients with mild to moderate hypertension. Furthermore, doxazosin treatment demonstrates a fewer number of withdrawals caused by adverse events.

Quality of life in dialysis patients. A spanish multicentre study. Spanish Cooperative Renal Patients Quality of Life Study Group.

The aim of this study was to evaluate the quality of life in patients on chronic dialysis and to research the influence of various factors related to treatment and ESRD on quality of life. The cross-sectional study was carried out nationally and 1013 randomly selected stable patients on dialysis were evaluated. The evaluation of quality of life was by the Karnofsky Scale (KS) and the Sickness Impact Profile (SIP). Both questionnaires were self-reported. Co-morbidity was evaluated according to the Friedman Comorbidity Index. Adjusted quality of life scores for case-mix differences of several groups of patients were compared. Twenty-six per cent of the patients showed severe quality of life restriction on the Global Score of SIP (score > or = 20) and 31% on the KS (score < or = 60). The partial categories of the SIP that were more affected were work, recreation and pastimes, home management, and sleep and rest. No significant differences were found relating to dialysis technique, dialysis solution, or dialyser membrane. Greater haemoglobin concentrations were related to better quality of life scores on Physical Dimension and Global Score of SIP. Advanced age and Comorbidity Index were related to worse quality of life scores. We conclude that 25% of the patients showed an important effect of the disease on their quality of life. An increase in haemoglobin was related to better quality of life in dialysis patients. Advanced age and co-morbidity both adversely affected quality of life.

The bone scan in patients with aluminium-associated bone disease.

The bone scans of 32 patients on regular dialysis who received desferrioxamine therapy for fracturing osteomalacia secondary to aluminium intoxication are reviewed. All scans show the same pattern, with lack of tracer deposition in bone and deposition in soft tissues. Therapy with desferrioxamine controlled the aluminium intoxication in all cases, and in 21 patients the bone scan reverted to normal or showed a pattern typical of hyperparathyroidism.