Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study.

BACKGROUND: Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF. METHODS: One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A-B and B-A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored. RESULTS: In sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P < 0.01. A multiple linear model confirmed that Mixed HDF vs Post-HDF reduced significantly ESA requirement and ESA resistance (P < 0.0001), by a mean of 29% (CI 23-35%) in the last three months of the observation periods. CONCLUSIONS: Mixed HDF decreased darbepoetin-alfa requirement in dialysis patients. This might help preventing the untoward side effects of high ESA doses, besides having a remarkable economic impact. Additional evidence is needed to confirm this potential benefit of Mixed-HDF.

Effects of high-volume online mixed-hemodiafiltration on anemia management in dialysis patients.

BACKGROUND: Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF). METHODS: We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models. RESULTS: Mean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 [Q1:0;Q3:16000] IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 [Q1:0;Q3:16000] vs 8000 [Q1:0;Q3:20000] IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687). CONCLUSIONS: Results of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF.

Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux haemodialysis, haemofiltration and haemodiafiltration: results of a multicentre randomized and controlled trial.

BACKGROUND: Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes. METHODS: Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients). RESULTS: CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta(2) 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta(2) 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170). CONCLUSIONS: In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.

On-line hemodiafiltration: technique and efficiency.

Hemodiafiltration (HDF) is the strategy enabling the high potential of hydraulic and solute permeability of synthetic membranes to be most properly exploited. On-line production of unlimited amount of sterile dialysate at low cost has favored its extensive diffusion in the recent years. However, to achieve the most efficient convective transport, ultrafiltration rate must be forced towards its physical limits, paying attention to the safety of the patient and to the integrity of the system. The infusion mode variably influences the dialyzer performance and the efficiency of the technique. With respect to standard and high-flux hemodialysis (HD), increased removal of solutes in the small and middle molecular weight range was reported with on-line HDF in several recent studies. Some of these compounds have a pathogenic role or are markers of the most frequent long-term complications and causes of death in HD patients, such as dialysis related amyloidosis, cardiovascular disease, inflammation and malnutrition. Even in the absence of definite evidence, coming from large data base studies, there are strong indications to advise the use of this dialytic strategy, which combines the benefits of the high biocompatibility of the membrane and the sterile dialysis fluid with increased removal by convection of middle-molecular uremic toxins. A new mode of infusion in on-line HDF--the mixed infusion mode--is here described, which is able to achieve and maintain the maximum possible water and solute removal during the sessions through a feedback control of the transmembrane pressure.