Characterization of recombinant OspA in two different Borrelia vaccines with respect to immunological response and its relationship to functional parameters.

BACKGROUND: Prevention of Lyme disease in dogs in North America depends on effective vaccination against infection by the tick vector-born spirochete Borrelia burgdorferi. Most vaccines effectively prevent spirochete transmission to dogs during tick feeding based on immunization with the outer-surface lipoprotein A (OspA) of B. burgdorferi. More recently, vaccines containing additional OspC protein moieties have been introduced. These are designed to enhance protection by forming a second line of defense within the vertebrate host, where OspC expression replaces OspA as the dominant surface antigen. However, supportive data for demonstration of OspC mediated protection is still lacking. Since OspA immunogenicity is of paramount importance to protection against spirochete transmission; this study was designed to compare the immunogenicity of two commercially available vaccines against the Borrelia burgdorferi OspA. We further characterized OspA antigen fractions of these vaccines with respect to their biochemical and biophysical properties. RESULTS: Two groups of beagle dogs (n = 9) were administered either: (1) a nonadjuvanted/monovalent, recombinant OspA vaccine (Recombitek® Lyme) or (2) an adjuvanted, recombinant OspA /OspC chimeric fusion vaccine (Vanguard® crLyme). The onset of the anti-OspA antibody response elicited by the nonadjuvanted/monovalent OspA vaccine was significantly earlier than that for the bivalent OspA /OspC vaccine and serum borreliacidal activity was significantly greater at all post-vaccination time points. As expected, only dogs inoculated with the bivalent OspA/OspC vaccine mounted a humoral anti-OspC response. However, only three out of nine dogs in that group had a positive response. Comparison of the OspA vaccine structures revealed that the OspA in the nonadjuvanted/monovalent vaccine was primarily in the lipidated form, eluting (SEC-HPLC) at a high molecular weight, suggestive of micelle formation. Conversely, the OspA moiety of the OspA/OspC vaccine was found to be nonlipidated and eluted as the monomeric protein. CONCLUSIONS: We hypothesize that these structural differences may account for the superior immunogenicity of the nonadjuvanted monovalent recombinant OspA vaccine in dogs over the adjuvanted OspA fraction of the OspA/OspC vaccine.

Microbiota Quality and Mitochondrial Activity Link with Occurrence of Muscle Cramps in Hemodialysis Patients using Citrate Dialysate: A Pilot Study.

BACKGROUND/AIMS: Hemodialysis-associated muscle cramp (HAMC) is a common complication under citrate dialysate (CD) occurring in 30% of cases. Our objectives were to assess the gut microbiota quality, mitochondrial activity, and to investigate their possible relationship with HAMC. METHODS: Ten end-stage renal disease patients (78.9 ± 2.1 years) treated by hemodialysis (HD) with CD were enrolled and then classified according to the frequency of HAMCs: "frequent HAMCs group" (n = 5) and "absence of HAMCs group" (n = 5). Gut microbiota quality, mitochondrial activity, and some markers of oxidative stress (OS) were investigated. RESULTS: In patients with cramps, gut microbiota diversity seemed lower and some genera including Helicobacter, Lachnospira, Roseburia, and Haemophilus seemed over-expressed, a significant increase of citratemia and significant lowering mitochondrial function were observed. No difference was observed on the OS markers. CONCLUSION: This first clinical study revealed a possible dysbiosis of microbiota and a mitochondrial dysfunction into HD patients with cramps under CD compared to patients without cramp.

CD4+ T cells and Lactobacillus casei control relapsing colitis mediated by CD8+ T cells.

Evidence that CD4(+) regulatory T cells can control Ag-specific CD8(+) T cell-mediated colitis in immunocompetent mice is poorly documented. To examine the potential of CD4(+) T cells to control colitis, we used our model of CD8(+) T cell-mediated colitis induced by intracolonic sensitization followed by challenge with the hapten 2,4-dinitrobenzene sulfonic acid. The defect of CD4(+) T cells in MHC class II-deficient (Abeta(degrees/degrees)) mice allowed priming of 2,4-dinitrobenzene sulfonic acid-specific IFN-gamma-producing CD8 colitogenic effectors and development of colitis in the otherwise resistant C57BL/6 strain. Cotransfer experiments in RAG2(degrees/degrees) mice and ex vivo studies showed that CD4(+)CD25(+) T cells completely prevented CD8(+) T cell-mediated colitis and controlled CD8(+) T cell activation, respectively. In the susceptible BALB/c strain, Ab depletion revealed that lack of CD4(+) regulatory T cells resulted in 1) acute colitis elicited by a suboptimal dose of hapten challenge and 2) more severe relapsing episodes of colitis induced by effector/memory CD8(+) T cell-mediated colitis at an optimal dose of hapten challenge, even when CD4 depletion was performed just before the second challenge. Oral administration of the probiotic strain Lactobacillus casei DN-114 001 alleviated colitis and increased the suppressive function of Foxp3(+)CD4(+) regulatory T cells of colon lamina propria. These data demonstrate that CD4(+) regulatory T cells exert a protective effect on colitis by controlling colitogenic effector/memory CD8(+) T cells during the effector (symptomatic) phase of acute and relapsing colitis, respectively. Probiotics with natural adjuvant effects on mucosal regulatory T cells may represent a valuable approach to alleviate the colitogenic effect of Tc1-type CD8(+) effectors.

ß-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs.

The mechanisms of trained immunity have been extensively described in vitro and the beneficial effects are starting to be deciphered in in vivo settings. Prototypical compounds inducing trained immunity, such as ß-glucans, act through epigenetic reprogramming and metabolic changes of innate immune cells. The recent advances in this field have opened new areas for the development of Trained immunity-based adjuvants (TIbAs). In this study, we assessed in dogs the potential immune training effects of ß-glucans as well as their capacity to enhance the adaptive immune response of an inactivated rabies vaccine (Rabisin®). Injection of ß-glucan from Euglena gracilis was performed 1 month before vaccination with Rabisin® supplemented or not with the same ß-glucan used as adjuvant. Trained innate immunity parameters were assessed during the first month of the trial. The second phase of the study was focused on the ability of ß-glucan to enhance adaptive immune responses measured by multiple immunological parameters. B and T-cell specific responses were monitored to evaluate the immunogenicity of the rabies vaccine adjuvanted with ß-glucan or not. Our preliminary results support that adjuvantation of Rabisin® vaccine with ß-glucan elicit a higher B-lymphocyte immune response, the prevailing factor of protection against rabies. ß-glucan also tend to stimulate the T cell response as shown by the cytokine secretion profile of PBMCs re-stimulated ex vivo. Our data are providing new insights on the impact of trained immunity on the adaptive immune response to vaccines in dogs. The administration of ß-glucan, 1 month before or simultaneously to Rabisin® vaccination give promising results for the generation of new TIbA candidates and their potential to provide increased immunogenicity of specific vaccines.

Regional discrepancies in peritoneal dialysis utilization in France: the role of the nephrologist's opinion about peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is underused in France compared with other countries. In addition, there are tremendous regional discrepancies concerning the utilization rate of PD. This study was carried out to evaluate the opinion of French nephrologists regarding the optimal rate of PD utilization and to determine which factors limit PD development in France. METHODS: Of the 22 French regions, 2 regions with a high rate of PD utilization (prevalence >15%) and 3 regions with a low rate of PD utilization (prevalence <10%) were selected. In June 2007, nephrologists from the five regions were surveyed by questionnaire. Responses were compared between 'low-prevalence' and 'high-prevalence' groups. RESULTS: The response rate was 70% and there was no significant difference between the two groups regarding the response rate. In the two groups, a majority of nephrologists were in charge of PD patients (30/34 in 'high-prevalence' group versus 61/80 in 'low-prevalence' group, P = 0.14). Information about PD in the predialysis clinics was provided by nephrologists from high- and low-prevalence regions (32/34 versus 65/80, P = 0.08). Opinions on the optimal rate of PD for prevalent and incident dialysis patients were significantly different between 'high-prevalence' and 'low-prevalence' groups [31 +/- 15% versus 25 +/- 14% (P < 0.03) and 25 +/- 14% versus 19 +/- 9% (P < 0.02)]. There was a significant difference concerning the optimal rate of PD in incident dialysis patients between nephrologists working in public centres (29 +/- 15%), those working in non- profit clinics (27 +/- 12%) and nephrologists working in the private sector (14 +/- 8%). Lack of nurses available for the patient care (48%), low reimbursement of PD (25%), limited training (23%) and hospital care facilities (23%) were the main barriers limiting PD utilization. CONCLUSIONS: In France, like in other countries, there are factors limiting PD development; however, regional discrepancies regarding PD utilization seem to be linked to the nephrologist's opinion.

Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models.

Microparticles and nanoparticles prepared with poly(D,L-lactide-co-glycolide) (PLGA) or poly(D,L-lactide) (PLA) polymers represent a promising method for in vivo delivery of encapsulated peptide, protein or DNA antigens. However, one major issue that limits the potential of these delivery systems is the instability or the degradation of the entrapped antigen. Charged microparticles carrying surface adsorbed antigen were developed to resolve this problem and appear more suitable for vaccine applications. We describe here new anionic PLA nanoparticles obtained by the dialysis method that are absolutely surfactant-free, which makes them more appropriate for use in humans. The potency of this delivery system as a vaccine carrier was tested in various animal models using HIV-1 p24 protein. p24-coated PLA nanoparticles (p24/PLA) induced high antibody titres (>10(6)) in mice, rabbits and macaques. Moreover, p24/PLA nanoparticles elicited strong CTL responses and a Th1-biased cytokine release (IFNgamma, IL-2) in mice. p24 protein seemed to generate a more Th1-oriented response when administered coated onto the surface of PLA nanoparticles than adjuvanted with Freund's adjuvant. Most importantly, the ability of p24/PLA particles to induce Th1 responses was also confirmed in the macaque model, since high levels of IFNgamma-producing CD4+ T cells and CD8+ T cells could be detected by the ELISPOT assay. This protein delivery system confirms the potential of charged nanoparticles in the field of vaccine development.

Impact of first dialysis modality on outcome of patients contraindicated for kidney transplant.

BACKGROUND: We compared, in patients contraindicated for kidney transplant, outcomes between those patients who were only on hemodialysis (HD) and those who were given peritoneal dialysis (PD) as first renal replacement therapy (RRT). DESIGN: Prospective, population-based cohort study of incident cases of end-stage renal disease between June 1997 and June 1999. SETTING: A network of dialysis care: NEPHROLOR, that is, all the renal units in Lorraine, one of the 22 French administrative regions (population over 2.3 million people). PARTICIPANTS: 387 patients were contraindicated for kidney transplant during the first 2 years of RRT: 284 were on HD, 103 on PD. Mean age was 67.6 +/- 11.3 years for HD patients and 70.8 +/- 11.4 years for PD patients (p = 0.015). MAIN OUTCOME MEASURES: Mortality until June 2003, hospitalization over the 2 first years of RRT, and Kidney Disease and Quality of Life Short Form (KDQOL-SF) 6 and 12 months after initiation of RRT. RESULTS: HD patients were more likely to die from cardiac or cerebrovascular causes, PD from cachexia or withdrawal from dialysis. Whatever mode of RRT, the unadjusted 2-year and 5-year survival rates were similar (p = 0.98). The rate of total duration of hospital stay per month of RRT was similarin HD and PD groups: 2.7 +/- 4.5 and 2.9 +/- 4.2 days respectively (p = 0.7). PD was associated with better quality of life than HD. The dimensions Role limitation due to emotional function, Burden of kidney disease, and Role limitation due to physical function ranked first, second, and third for PD. CONCLUSION: In Lorraine, end-stage renal disease patients who were given PD as first-line RRT had no excess of death risk or hospitalizations, and better quality of life the first year of RRT.

[Iron therapy: is it different with peritoneal dialysis compared to haemodialysis?]. / Le traitement martial est-il différent en hémodialyse et en dialyse péritonéale?

This paper reviews literature data on iron replacement (loading) for peritoneal dialysis patients. The 3 main sources of clinical guidelines (American NKF-K/DOQI, European EBPG and French AFSSAPS) agree about the definition of iron deficience, but are not similar about the haemoglobin/hematocrit targets for EPO treatment, and for the route of iron administration (oral versus intravenous). Iron requirements are less in PD HD patients. That could be explained by several factors: less blood losses, preservation of a residual renal function, better digestive iron absorption due to a greater hepcidin excretion. Intravenous route for iron sucrose is more efficient than oral route. Taking into account the iron requirements for PD patients, monthly 200 mg iron sucrose infusions over 5 mn seem to be safe and sufficient for most patients.

Short communication: retrospective study to time the introduction of HIV type 1 non-B subtypes in Lyon, France, using env genes obtained from primary infection samples.

Using blood samples from primary HIV-1 infection (PHI) patients obtained in Lyon, France, we characterized the newly transmitted HIV-1 variants in this area during the 1992-1996 period. As PHI samples allowed the precise timing of the transmission event, we were able to date the introduction of non-B subtypes or recombinant forms of the virus in Lyon. Genomic DNA from 18 HIV-1-positive patients at primary infection was used to amplify the full-length env gene by nested PCR; after cloning, the gene was sequenced for subsequent phylogenetic analysis. Several non-B subtypes and recombinant forms of HIV-1 were identified among the 18 patients studied (1 subtype F1, 1 CRF01-AE, 2 subtype G and 2 CRF02-AG). We also found a new J/K recombinant form transmitted in 1995 and never described until now. The introduction of CRF02-AG in Lyon, France, occurred prior to 1992 and six transmission events including non-B subtypes were documented in the following 4 years. Heterosexual contacts appeared as the main introduction pathway for non-B subtypes or recombinant forms. Nevertheless, as transmission of these viruses occurred not only during travel to endemic regions, but also in France or Germany, we conclude that non-B strains entered Europe before the studied period. This retrospective study showed that even if subtype B remained prevalent in the spreading HIV-1 infection in Lyon between 1992 and 1996, non-B subtypes and circulating recombinant forms represented a significantly growing part.

Evaluation in rhesus macaques of Tat and rev-targeted immunization as a preventive vaccine against mucosal challenge with SHIV-BX08.

Recent evidence suggests that a CD8-mediated cytotoxic T-cell response against the regulatory proteins of human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) may control infection after pathogenic virus challenge. Here, we evaluated whether vaccination with Tat or Tat and Rev could significantly reduce viral load in nonhuman primates. Rhesus macaques were primed with Semliki forest Virus (SFV) expressing HIV-1 tat (SFV-tat) and HIV-1 rev (SFV-rev) and boosted with modified vaccinia virus Ankara (MVA) expressing tat and rev. A second group of monkey was primed with SFV-tat only and boosted with MVA-tat. A third group received a tat and rev DNA/MVA prime-boost vaccine regimen. Monitoring of anti-Tat and anti-Rev antibody responses or antigen-specific IFN-gamma production, as measured by enzyme-linked immunospot assays revealed no clear differences between the three groups. These results suggest that priming with either DNA or SFV seemed to be equivalent, but the additive or synergistic effect of a rev vaccine could not be clearly established. The animals were challenged by the rectal route 9 weeks after the last booster immunization, using 10 MID(50) of a SHIV-BX08 stock. Postchallenge follow-up of the monkeys included testing seroconversion to Gag and Env antigens, measuring virus infectivity in PBMC by cocultivation with noninfected human cells, and monitoring of plasma viral load. None of the animals was protected from infection as assessed by PCR, but peak viremia was reduced more than 200-fold compared to sham controls in one third (6/18) of vaccinated macaques, whatever the vaccine regimen they received. Interestingly, among these six protected animals four did not seroconvert. Altogether, these results clearly indicated that the addition of early HIV proteins like Tat and Rev in a multicomponent preventive vaccine including structural proteins like Env or Gag may be beneficial in preventive vaccinal strategies.

[Focusing on peritoneal dialysis adequacy]. / Adéquation en dialyse péritonéale : mise au point.

The optimal method to assess the adequacy of peritoneal dialysis therapies is controversial. Today, the adequacy must not be considered as a number or a concept assessed only by two parameters (total KT/V urea and total solute clearance) but defined by many more items. In the absence of data, based on theoretical considerations, the reanalysis of the CANUSA study showed that renal kidney function, rather than peritoneal clearance, was associated with improved survival. Residual renal function is considered as a major predictor factor of cardiovascular mortality. Results of this reanalysis were supported by the adequacy data in ADEMEX, EAPOS and ANZDATA studies. Therefore, clinical assessment plays a major role in PD adequacy. The management of fluid balance, the regular monitoring of malnutrition, the control of mineral metabolism and particularly the glucose load, considered as the "corner-stone" of the system, are the main points to be considered in the adequacy of PD patients. The essential goal is to minimize glucose load by glucose-sparing strategies in order to reduce the neoangiogenesis of the peritoneal membrane.

Blockade of LTB(4) /BLT(1) pathway improves CD8(+) T-cell-mediated colitis.

BACKGROUND: Leukotriene B4 (LTB(4) ) has chemotactic properties for activated T cells expressing the high-affinity receptor BLT(1) . This study investigated whether the LTB(4) antagonist (CP-105,693), selective for BLT(1) receptor, could protect mice from colitis mediated by specific cytotoxic CD8(+) T lymphocytes (CTL). METHODS: Virus-specific colitis was induced in C57Bl/6 mice transferred with lymphoid cells from P14 TcR Tg mice which are specific to class I GP33 peptide of LCMV. Mice were immunized with GP33-pulsed dendritic cells and colitis was elicited by intrarectal administration of the peptide. Colitis was evaluated by body weight loss and macroscopic and histological analysis of colon. In vivo priming of specific CD8(+) CTL was determined using interferon (IFN)-γ ELISPOT and in vivo CTL assays. In some experiments mice were treated with a selective LTB(4) receptor antagonist. RESULTS: Immunization with GP33-pulsed dendritic cells (DCs) induced priming of specific CD8(+) CTL, as shown by the presence of IFN-γ-producing CD8(+) T cells in colon draining lymph nodes and in vivo CTL assays. Intrarectal challenge with GP33 induced severe colitis and recruitment of granzyme B(+) P14 CD8(+) cells in colon. Treatment with the specific LTB(4) receptor antagonist before elicitation of colitis reduced the severity of colitis and decreased the frequency of specific effectors. CONCLUSIONS: Colitis can be induced by IFN-γ-producing cytotoxic CD8(+) CTL specific for viral antigen. Blockade of the LTB(4) /BLT(1) pathway by a selective BLT(1) receptor antagonist attenuates colitis by inhibiting CD8(+) effectors recruitment in colon. These data illustrate the therapeutic potential of LTB(4) receptor selective antagonists in protection from CD8(+) T-cell-mediated intestinal inflammation.

Changes in health-related quality of life in patients of self-care vs. in-center dialysis during the first year.

OBJECTIVE: In the Lorraine area (France), dialysis centers propose an educational program to improve patient's ability to perform dialysis by themselves. The objective was to assess changes in health-related quality of life (HRQoL) during the first year of dialysis, comparing independent patients with patients on in-center dialysis. METHOD: All patients aged between 18 and 70 and having started their first dialysis between June 1997 and June 1999 in the Lorraine area were included. Socio-demographic, medical data and HRQoL (KDQoL) were assessed for each patient at enrollment, at 6 and 12 months. RESULTS: At 12 months, 195 patients were in dialysis, 147 were non-autonomous, and 48 were autonomous. Independent patients were younger, were more often in occupational activity, had a lower body mass index and had fewer comorbidities. Several dimensions of the HRQoL were significantly higher in autonomous patients at baseline: physical functioning (60.4 vs. 50.7) and work status (30.9 vs. 18.4); and at 12 months: less burden of kidney disease (51.7 vs. 37.3), fewer effects of kidney disease (65.9 vs. 54.0), cognitive function (72.0 vs. 62.7) and role-emotional (53.0 vs. 34.5). CONCLUSION: These results show improved HRQoL among independent patients. Our regional care network may be a particularly useful model for undertaking actions motivating the healthcare teams and for enhancing the human resources devoted to patient education.

Influence of autonomy and type of home assistance on the prevention of peritonitis in assisted automated peritoneal dialysis patients. An analysis of data from the French Language Peritoneal Dialysis Registry.

BACKGROUND: In France, 48% of home-based peritoneal dialysis (PD) patients require assistance to perform their exchange and manage their treatment. A total of 7% are aided by their family, and 41% by a private nurse. Of all the continuous ambulatory peritoneal dialysis (CAPD) patients, 61.7%, and among automated peritoneal dialysis (APD) patients 23%, are assisted at home for their bag exchanges and connections. Assisted APD patients (AAPD) are more comorbid and elderly so that a home helper is not always available: this explains why most helpers at home are private visiting nurses paid by the National Social Security. In addition to the home helper (nurse or family), 58% of centres make regular additional home visits to check the respect of procedures previously taught during the initial training of the nurse or the family helper. The aim of this study was to evaluate whether the type of home assistance received by dependent patients had an influence on peritonitis rates, and if home visits done by nurses of training centres may improve results. METHODS: Peritonitis rates and the probability of being peritonitis free were analysed for 1624 new APD patients recorded in the French PD Registry (RDPLF) between 2000 and 2004, and followed-up until early 2005. RESULTS: Nurse-assisted APD patients had a peritonitis rate of one episode every 36 months, and family-assisted patients one episode every 45 months; using Poisson analysis this trend was not significant (P=0.11). However, the probability of being peritonitis free was significantly higher for family-assisted (69.8% at 2 year) compared with home nurse-aided persons (54.4%) after adjustment for age, diabetes and the Charlson comorbidity index. This difference disappeared when nurses from the training centre regularly visited PD patients at their home in the presence of their helper, whichever type of assistance they received. In addition, when the nurses from the training centres visited private nurse-assisted patients, the probability of being peritonitis free was significantly improved in comparison with those persons who did not receive home visits, from 33.9% to 50.8% at 3 years (P=0.028). CONCLUSIONS: APD patients assisted at home by a private nurse have a higher risk of developing peritonitis than family-assisted patients, unless additional regular home visits are organized by the original training centre. Therefore, we recommend that home visits be regularly made for dependent PD patients to optimize the quality of care provided by the helper.

APD schedules and clinical results.

This chapter exposes the clinical effects of different APD schedules. Clinical studies have shown that Na removal is lower with APD compared to CAPD. Therefore the loss of residual renal function requires continuous therapy with long day-dwell of polyglucose dialysate. Peritoneal small molecule clearances are closely determined by the hourly dialysate flow rate (and not the dwell time, which is a concept coming from equilibrium PD techniques as CAPD) with a maximum reached by 3 l/h for average transporter patients. On the other hand, the optimal intraperitoneal volume should be 1500 ml/m(2) of BSA, and less if the hydrostatic intraperitoneal pressure is higher than 18 cm H(2)O. The optimization of the nocturnal APD session depends on the knowledge of the individual drain flow profile. A new schedule, called 'BreakPoint-APD' is based on the automatic adaptation to the drain profile for each patient and for each cycle. It increases clearances by about 10% compared to tidal and CCPD, though reducing the number of nocturnal alarms. The future of APD is likely to continue thanks to further simplification in the machine use, i.e. with improvements in cycler technology.

The efficacy and safety of once-weekly and once-fortnightly subcutaneous epoetin beta in peritoneal dialysis patients with chronic renal anaemia.

BACKGROUND: Reducing the dosage frequency of subcutaneous epoetin in peritoneal dialysis (PD) patients is convenient and should improve patient satisfaction and, possibly, compliance. We investigated if a weekly dosage of epoetin beta in PD patients safely maintained haemoglobin (Hb) concentrations equivalent to those obtained with previous twice- or thrice-weekly administration. In addition, we investigated if a fortnightly dosage of epoetin beta was safe and as effective as previous weekly administration. METHODS: After a 4 week run-in period, PD patients were switched to either weekly or fortnightly epoetin beta administration, depending on their previous treatment schedules, for 25 weeks. RESULTS: The per-protocol cohort included 128 patients, of whom 54 received epoetin beta once weekly and 74 once fortnightly. The mean change in Hb concentration from baseline over weeks 13-25 and the 90% confidence intervals (CIs) remained within the target range (10-12 g/dl) and specified equivalence (+/-0.75 g/dl) limits in the weekly (-0.34 g/dl; 90% CI: -0.14 to -0.54 g/dl) and fortnightly (-0.39 g/dl; 90% CI: -0.24 to -0.55 g/dl) cohorts. The mean change from baseline in the epoetin beta dose was 1.4 IU/kg/week (90% CI: -3.8 to 6.6 IU/kg/week; 2%) in the weekly cohort and 4.4 IU/kg/week (90% CI: 1.7-7.2 IU/kg/week; 13%) in the fortnightly cohort. Both treatment regimens were well tolerated. CONCLUSIONS: In stable PD patients switched from twice- or thrice-weekly to weekly epoetin beta treatment, Hb concentrations could be maintained within the specified range over 25 weeks without significant change in their mean epoetin beta doses. In patients switched from weekly to fortnightly treatment, Hb concentrations could also be maintained over 25 weeks. There was a small increase in the mean dose during this period, but >/=50% of patients could be maintained without dose increase. Reducing dosage frequency may improve compliance in PD patients who self-administer their epoetin.