Efficacy and safety of once-monthly continuous erythropoietin receptor activator in patients with chronic renal anemia.

BACKGROUND: In the management of anemia in patients with chronic kidney disease stage 5 undergoing dialysis (CKD-5D), maintaining hemoglobin (Hb) within the range recommended by the guidelines is challenging. METHODS: The CARISMA study aim was to evaluate the efficacy, safety and tolerability of a once-monthly continuous erythropoietin receptor activator (CERA) for the treatment of anemia in CKD-5D patients. In this single-arm, multicenter, open-label, phase IIIb study, we screened adult patients from 66 centers in Italy receiving intravenous epoetin alfa or beta or darbepoetin alfa. Eligible patients entered the CERA dose titration phase (DTP), followed by an efficacy evaluation period (EEP) and a long-term safety period (LTSP). Patients were analyzed by intention-to-treat (ITT), per protocol (PP) and safety populations. RESULTS: The rate of patients maintaining Hb within the range 10.0-12.0 g/dL throughout the EEP was 63.22% (220/348), and concentration from baseline to any postbaseline time point. CERA may thus offer a convenient and effective treatment 73.94% (122/165) in the ITT and PP population, respectively, periods in both populations. The rate of patients requiring a dose change was higher during the DTP (69.2%) and the LTSP (73.0%) than during the EEP (54.5%), as expected. CERA treatment was generally well tolerated. CONCLUSIONS: Once-monthly CERA administered to CKD-5D patients was associated with negligible changes in mean Hb option for these patients.

Sleep disorders in patients with end-stage renal disease undergoing dialysis therapy.

BACKGROUND: Many patients with end stage renal disease (ESRD) undergoing dialysis therapy suffer from sleep disturbances. The aim of this study was to investigate the prevalence of sleep disorders in a large population of uraemic patients recruited from 20 different dialytic centres in Triveneto. METHODS: 883 patients on maintenance dialysis were enrolled in the study. Demographic, lifestyle, renal and dialysis data were recorded. Renal parameters were compared with the database of the Veneto Dialysis Register. Using a self-administered questionnaire we assessed the presence of the following sleep disorders: insomnia, restless leg syndrome (RLS), obstructive sleep apnoea syndrome (OSAS), excessive daytime sleepiness (EDS), possible narcolepsy, sleepwalking, nightmares and possible rapid eye movement behaviour disorders (RBD). Moreover, in order to determine the prevalence of sleep disturbances and the possible effect of demographic or clinical data on sleep, we divided our population into two groups: with (SLEEP+) and without (SLEEP-) sleep disorders. RESULTS: The questionnaire revealed the presence of insomnia (69.1%), RLS (18.4%), OSAS (23.6%), EDS (11.8%), possible narcolepsy (1.4%), sleepwalking (2.1%), nightmares (13.3%) and possible RBD (2.3%). Eighty percent demonstrated SLEEP+, having at least one sleep disorder. Independent risk factors for sleep disorders were advanced age (P<0.001), excessive alcohol intake (P<0.04), cigarette smoking (P<0.006), polyneuropathy (P<0.05) and dialysis shift in the morning (P<0.001). CONCLUSIONS: The questionnaire showed a high presence of sleep disruption in dialytic populations. Awareness by Italian nephrologists regarding sleep disruption seems to be insufficient. Our data might help nephrologists to deal with uraemic patients with possible sleep disorders. Concerning the high prevalence of possible narcolepsy, further studies using polysomnographic records are necessary to confirm our results.

Restless legs syndrome in end-stage renal disease.

BACKGROUND AND PURPOSE: Patients undergoing dialysis therapy due to end-stage renal disease (ESRD) present a high prevalence of sleep disorders, including restless legs syndrome (RLS). However, the known data generally have been obtained from relatively small patient samples, coming from single or very few dialysis units. Moreover, some data were collected prior to the recent improvements in dialysis techniques, pharmacological therapies and to the establishment of internationally recognised diagnostic criteria for RLS. PATIENTS AND METHODS: In order to study the incidence of the different sleep disorders, and of RLS in particular, in a large population of dialysis patients, a questionnaire was administered to all the patients in dialysis units of the 'Triveneto' area (Italy) who agreed to participate. The first part of the questionnaire included questions about demographic data, general medical history, history of renal disease, dialytic treatment and pharmacological therapy. The second part, which was self-administered, explored the patient's complaints about sleep, the presence of the minimal International Restless Legs Syndrome Study Group (IRLSSG) criteria for the diagnosis of RLS, the Epworth Sleepiness Scale and questions particularly related to somnolence. Patients whose responses indicated a diagnosis of RLS according to the IRLSSG criteria were requested to answer the 10 questions of the IRLSSG Severity Scale. The same group of patients was compared to those who did not fulfil any of the four minimal criteria for RLS. Statistical analysis was performed by using ANOVA and non-parametric tests. Whenever possible, data were compared with the database of the Veneto Dialysis Register. The first 601 consecutive questionnaires that we were able to analyse are presented in this paper. RESULTS: Applying the IRLSSG criteria for the diagnosis, the percentage of RLS patients in our sample was 21.5%, with a score of 20.5+/-8.7 on the IRLSSG Severity Scale. Comparing patients who are definitely affected by RLS (n=127) with unaffected patients (n=280), we found that the two groups did not differ as to age, sex, weight, body mass index (BMI), and intake of nicotine, alcohol and caffeine. Similarly, the two groups did not differ as to the etiology of ESRD, type of dialysis or percentage of previous transplantations; however, the period of dialysis dependence was significantly lower in the group negative for RLS. The use of drugs did not differ in the two groups, except for lower intake of phosphorus binders and antihypertensive drugs among RLS patients. No patient was receiving specific treatment for RLS. RLS patients reported more fragmented, less restful nightly sleep and more daytime somnolence, more often presented symptoms of other sleep disorders and were more affected by anxiety or depression. CONCLUSIONS: The high prevalence of RLS and other sleep disorders among uremics requires careful investigation of nocturnal sleep; although often underdiagnosed, correct identification of these disorders can lead to better therapy and improvement of clinical conditions and quality of life. Sleep fragmentation and sleep deprivation caused by RLS may contribute to the cardiovascular complications and infections, often with bad prognosis in dialysis patients.