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.

[Central venous catheter lock to prevent thrombosis and bacterial infection]. / Il rebus del ''lock'' del catetere venoso centrale per la prevenzione della trombosi e delle batteriemie da catetere.

The permanent central venous catheter (CVCp) for vascular access is increasingly common in patients on hemodialysis. The main problem related to CVCp is the biofilm, which leads to malfunction and an increased risk of infections. In recent years lock solutions for the CVCp have become popular. Heparin should be abandoned because it induces rapid biofilm development and exposes the patient to the risk of bleeding due to overspill of heparin into the bloodstream. Citrate solution (3.8%) is associated with the best risk/benefit ratio for CVC functioning but offers no advantages in terms of reducing infections. The use of hypertonic citrate (46.7%) or antimicrobic solutions (AML) should be reserved for patients with a high incidence of infection and in cases where it is not possible to replace the CVCp. AML should be used for short periods only because of the risk of the development of resistance. The results of ongoing trials will be needed to establish the usefulness of the solution with ethanol. In the correct management of the CVCp, whichever lock solution is used, continuing staff training and widespread application of hygiene measures is of the utmost importance.

The middle-arm fistula as a valuable surgical approach in patients with end-stage renal disease.

BACKGROUND: American and European guidelines recommend the distal radial-cephalic fistula (dRCF) as the first and best hemodialysis access in patients with end-stage renal disease (ESRD). However, this kind of arteriovenous fistula (AVF) shows a limited primary unassisted patency and frequently needs surgical revisions or angiographic procedures, or both. When dRCF is not feasible, guidelines suggest a proximal brachiocephalic AVF. The middle-arm fistula (MAF), or autogenous forearm radial-median direct access, has been suggested as a possible alternative approach. This study evaluated MAF primary unassisted patency, the most frequent causes of MAF failure, and the possible related factors. METHODS: Data on patients with a MAF placed from January 1991 until June 2008 were retrospectively collected. The probability of MAF failure overall and by the main subgroups was estimated according to Kaplan-Meier with Greenwood standard error (SE). Comparison of failure among different subgroups was performed using the log rank test in univariate analyses. The Cox regression model was used to investigate factors that independently affected the overall hazard of failure and cause-specific hazard of thrombosis. RESULTS: At the end of follow-up, 14.0% of MAF failed (11.6% thrombosis, 1.7% stenosis, 0.7% failed maturation), and 44.2% of MAF were still working. Cumulative probability of MAF unassisted primary patency after 4 years from the creation was 79%. Univariate analyses highlighted that women (P = .019), underweight patients (P = .010), and MAF implantation after starting hemodialysis (P < .001) had a higher risk of MAF failure for any cause than men, normal and overweight patients, and MAF implanted before starting hemodialysis. Results of the Cox multivariate analysis for overall MAF failure confirmed that only MAF implantation before starting hemodialysis is a protective factor against any failure (P = .003), whereas female gender (P = .016) was associated with an increase of the thrombosis hazard ratio to 2.04 (95% confidence interval, 1.14-3.63). CONCLUSION: Our data demonstrate that MAF has a good unassisted primary patency and suggest that this kind of AVF could be a valuable alternative surgical approach when dRCF is not feasible in ESRD patients.

Modeling survival of arteriovenous accesses for hemodialysis: semiparametric versus parametric methods.

BACKGROUND AND OBJECTIVES: Comparing outcomes of arteriovenous grafts and fistulas is challenging because the pathophysiology of access dysfunction and failure rate profiles differ by access type. Studying how risks vary over time may be important. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Longitudinal data from 535 incident hemodialysis patients were used to study the relationship between access type and access survival, without (semiparametric Cox modeling) and with specification of the underlying hazard function (parametric Weibull modeling). RESULTS: The hazard for failure of fistulas and grafts declined over time, becoming proportional only after 3 months from surgery, with a graft versus fistula hazard ratio of 3.2 (95% confidence interval 1.9 to 5.3; Cox and Weibull estimation) and time ratio of 0.11 (i.e., the estimated access survival time was approximately one tenth shorter in grafts; 95% confidence interval 0.04 to 0.28; Weibull estimation only). Considering the entire observation period, grafts had slower hazard decline (P<0.001) with shorter median survival times than fistulas (8.4 versus 38.3 months; Weibull regression only). CONCLUSIONS: Parametric models of arteriovenous access survival may provide relevant information about temporal risk profiles and predicted survival times.

A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent versus synthetic adrenocorticotropic hormone in idiopathic membranous nephropathy.

BACKGROUND: We conducted a pilot trial to compare the effectiveness and safety of 2 different treatments in patients with membranous nephropathy and nephrotic syndrome. METHODS: To validate the hypothesis that the 2 treatments were equivalent, patients with biopsy-proven membranous nephropathy and nephrotic syndrome were randomly assigned to methylprednisolone alternated with a cytotoxic drug every other month for 6 months (group A) or to intramuscular synthetic adrenocorticotropic hormone administered twice a week for 1 year (group B). RESULTS: The primary outcome measure is cumulative number of remissions as a first event. Fifteen of 16 patients in group A and 14 of 16 patients in group B entered complete or partial remission as a first event. After a median follow-up of 24 months (interquartile range, 15 to 25 months), there were 4 complete remissions and 8 partial remissions in group A versus 8 complete remissions and 6 partial remissions in group B. Median proteinuria decreased from protein of 5.1 g/d (interquartile range, 4.0 to 7.3 g/d) to 2.1 g/d (interquartile range, 0.4 to 3.8 g/d; P = 0.004) in group A and 6.0 g/d (interquartile range, 4.4 to 8.5 g/d) to 0.3 g/d (interquartile range, 0.2 to 1.9 g/d; P = 0.049) in group B. Two patients from each group interrupted treatment because of side effects or inefficacy. CONCLUSION: Most nephrotic patients with membranous nephropathy responded to either treatment. Proteinuria was significantly decreased with both methylprednisolone and cytotoxic agents or prolonged administration of synthetic adrenocorticotropic hormone, without significant differences between these 2 therapies.