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Hemodiafiltration with endogenous reinfusion of the ultrafiltrate (HFR) is a dialysis technique characterized by a resin cartridge with adsorptive properties that combines the mechanisms of diffusion, convection, and adsorption in a single therapeutic regimen. After nearly 20 years of clinical experience with HFR, this article reviews the accumulated evidence with this technique, considering whether adsorption reduction, as a third purification mechanism, should be the next step in the treatment of hemodialysis patients. HFR, beyond producing an extensive removal of uremic toxins, has demonstrated to reduce the loss of nutrients and other physiological components during the dialysis session as compared to online hemodiafiltration, ameliorating the inflammatory state and oxidative stress in this population. In addition to its ease of use, the technique is also highly biocompatible and can be used in patients with a compromised vascular access. Based on these observations, HFR appears to be an especially useful therapy for high-comorbidity patients, including those with frailty, malnutrition, or cardiovascular disease. In this review, we, as a consensus panel of nephrologists experienced with HFR, survey existing literature and summarize our views on when to use this technique, which patients may be best suited for HFR, and how to effectively prescribe and monitor this modality of dialysis in daily clinical practice., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Acute kidney injury (AKI) occurs in 12-20% of multiple myeloma (MM) patients. Several studies have shown a reduction of free light chains (FLC) using hemodialysis with High-Cut-Off membranes. However, this technique entails albumin loss. Hemodiafiltration with ultrafiltrate regeneration is a technique that includes a process of adsorption. The aim of this study was to evaluate the effectiveness of hemodiafiltration with ultrafiltrate regeneration in reducing FLC levels without causing albumin loss., Methods: This is an observational study (2012 to 2018) including nine patients with MM (5 kappa, 4 lambda) and AKI. All patients were treated with chemotherapy and hemodiafiltration with ultrafiltrate regeneration. Blood Samples (pre and post-dialysis) and ultrafiltrate were collected pre and post-resin at 5 min after initiation of the session and 5 min before the end of the procedure., Results: The serum levels of kappa and lambda were reduced by a 57.6 ± 10% and 33.5 ± 25% respectively. Serum albumin concentration remained unchanged after the procedure. In the ultrafiltrate, the mean FLC reduction ratio shortly after initiation of the dialysis procedure was: 99.2 and 97.06% for kappa and lambda respectively, and only 0.7% for albumin; and at the end of the session the percent reduction was: 63.7 and 33.62% for kappa and lambda respectively, and 0.015% for albumin. Patients clinical outcome was: 33.3% recovered renal function, 22.2% died during the first year and 44.4% required maintenance dialysis., Conclusions: Hemodiafiltration with ultrafiltrate regeneration reduces FLC levels without producing a significant loss of albumin; and, FLC removal is maintained throughout the session. Therefore, hemodiafiltration with ultrafiltrate regeneration may be considered an effective adjunctive therapy in patients with MM.

Hemodiafiltration with endogenous reinfusion (HFR) after ultrafiltrate passage through a resin cartridge combines adsorption, convection, and diffusion. Our prospective single-center crossover study compared HFR and online-hemodiafiltration (OLHDF) effects on two uremic toxins and 13 inflammatory, endothelial status, or oxidative stress markers. After an 8-week run-in period of high-flux hemodialysis, 17 eligible stable dialysis patients (median age 65 years, 10 male) without overt clinical inflammation were scheduled for four 8-week periods in the sequence: HFR/OLHDF/HFR/OLHDF. Relative to OLHDF, HFR was associated with greater indoxyl sulfate removal and lesser abnormalities in all other study variables, namely circulating interleukin-6, tumor necrosis factor-alpha, proportions of activated proinflammatory (CD14+CD16+, CD14++CD16+) monocytes, endothelial progenitor cells, apoptotic endothelial microparticles, vascular endothelial growth factor, vascular cellular adhesion molecule, angiopoietins 2 and 1, annexin V, and superoxide dismutase. Differences were significant (P < 0.05) in median values of 13/15 variables. Study period comparisons were generally consistent with dialysis technique comparisons, as were data from the subgroup completing all study periods (n = 9). Our investigation provides hypothesis-generating results suggesting that compared with OLHDF, HFR improves protein-bound toxin removal, inflammatory and endothelial status, and oxidative stress., (© 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Acute kidney failure in multiple myeloma (MM) occurs in 12%-20% of patients and is a poor prognostic factor for patient survival. Recent studies have shown that dialysis with a High-Cut-Off membrane (HCO) removes free light chains (FLC) effectively although with significant albumin loss. Other adsorption-based techniques, such as haemodiafiltration with ultrafiltrate regeneration by adsorption in resin (SUPRA-HFR), have not been studied. We present three cases of MM, all haemodialysis-dependent since diagnosis. Two cases were IgG kappa and one was IgA lambda. All patients were treated with chemotherapy and SUPRA-HFR. The aim of this study was to evaluate the effectiveness of SUPRA-HFR in the reduction of FLC and its effect on albumin. We collected blood samples pre- and post-dialysis, and ultrafiltrate (UF) samples pre- and post-resin 5 minutes into the session and 5 minutes from the end. The mean reduction rate of FLC in blood per session in the three patients was 53% and 63% (kappa) and 38% (lambda). In the UF, the mean FLC reduction rate was close to 99%, both at the start and at the end of dialysis, without the removal of albumin. With the results obtained we can conclude that this technique achieves an effective reduction of FLC, which is maintained throughout the session, without resin saturation and without albumin loss. Therefore, SUPRA-HFR is effective as an adjunctive therapy for MM.

Background: Patients must receive an adequate dialysis dose in each hemodialysis (HD) session. Ionic dialysance (ID) enables the dialysis dose to be monitored in each session. The aim of this study was to compare the achievement of Kt versus eKt/V values and to analyse the main impediments to reaching the dialysis dose., Methods: Of 5316 patients from 54 Fresenius Medical Care centers in Spain undergoing their usual HD regime, 3275 received ID and were included in the study., Results: The minimum prescribed dose of eKt/V was reached in 91.2% of the patients, while the minimum recommended dose of Kt was reached in only 66.8%. Patients not receiving the minimum Kt dose were older, had spent 7 months less on dialysis, had a dialysis duration of 6 min less, had 5.7 kg more of body weight and Qb was 47 mL/min lower. The target Kt was not reached by 62% of patients with catheters and by 37% of women. With each quintile increase of body weight, eKt/V decreased and Kt increased. Of patients with a body weight >80 kg, 1.4%, mostly men, reached the target Kt but not prescribed eKt/V., Conclusions: The impact of monitoring the dose with Kt instead of Kt/V is that identifies 25.8% of patients who did not reach the minimum Kt while achieving Kt/V. The main impediments to achieving an adequate dialysis dose were catheter use, female sex, advanced age, greater body weight, shorter dialysis time and lower Qb.

Background/aims: We examined the effects of different online hemodiafiltration techniques on microinflammation and endothelial damage/repair., Methods: The study was designed as a prospective crossover study. Flow cytometry was used to measure CD14(+)CD16(+) monocytes, apoptotic endothelial microparticles (EMPs), and endothelial progenitor cells (EPCs)., Results: Patients treated with high-flux hemodialysis showed a marked chronic inflammatory state (HF-HD 11 ± 2) versus healthy subjects (HS 3.9 ± 2.3; p < 0.05). High convective transport, independent of the technique used, improves microinflammatory parameters (OL-HDF 7.3 ± 2.1 or MID 6.5 ± 3.4; p < 0.05) and the endothelial damage/repair balance compared to HF-HD (EPCs HF-HD 0.3 ± 0.2), with no differences found between the two modalities (EPCs OL-HDF 0.6 ± 0.1, MID 0.6 ± 0.2; p < 0.05)., Conclusion: An increase in convective transport improves the microinflammatory state and the endothelial damage/repair of these patients independently of the technique used., (Copyright © 2013 S. Karger AG, Basel.)

Chronic inflammation presented by chronic kidney disease patients is accompanied by an increase in the percentage of CD14+/CD16+ monocytes. The inflammatory activity produced by these cells provokes the activation and death of endothelial cells, which suggests that these cells may play an important role in the coupling of inflammation and endothelial damage in these patients. Therefore, the reduction in CD14+/CD16+ inhibitory monocytes may constitute a therapeutic goal in the treatment of chronic kidney disease patients. The use of the most effective hemodialysis techniques such as on-line hemodiafiltration appears to be a suitable tool for achieving this objective., (Copyright © 2011 S. Karger AG, Basel.)

Summary Background: The small quantity of acetate present in the dialysis fluid exposes patient's blood to an acetate concentration 30-40 times the physiological levels. This amount is even greater in hemodiafiltration on-line. Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient., Methods: 35 patients on hemodialysis were included. All patients were treated with conventional bicarbonate dialysate for 3 months, after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6 months or to invert the two last periods. Blood samples were drawn monthly throughout the study and clinical data were obtained., Results: Postdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate. Moreover, the percentage of patients with postdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period (61% vs. 30%). Serum concentrations of chloride postdialysis were higher and serum concentrations of bicarbonate pre and posthemodialysis were lower in the PHF free-acetate period. The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate., Conclusions: PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges. PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate.

It is not known whether high convective transport may have a role in modulating the chronic inflammation of hemodialysis (HD) patients. The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on proinflammatory peripheral monocytes: Percentage of CD14+CD16+ cells and their telomere length and spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6). In a prospective, crossover study, 31 patients who were on high-flux HD (HF-HD) were evaluated. Patients underwent the following sequence of treatments (4 mo each): HF-HD (basal), OL-HDF (period 1), HF-HD (period 2), OL-HDF (period 3), and HF-HD (period 4). The dialysis characteristics were similar in the two modalities; the only difference was a higher convective transport in the OL-HDF than in the HF-HD. All patients who were on OL-HDF periods showed a significantly lower number of CD14+CD16+ cells than on HF-HD (18.5 +/- 2.3 basal versus 13.6 +/- 2.9 period 1 and 13.9 +/- 2.3 period 3; P = 0.001). By contrast, HF-HD restored the number of CD14+CD16+ cells to the basal values (19.2 +/- 2.8 and 18.6 +/- 1.4, periods 2 and 4, respectively; NS). During OL-HDF periods, the reduction of CD14+CD16+ was paralleled by a decreased number of short telomere cells. Spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6) was increased in HF-HD as compared with OL-HDF. In conclusion, these results demonstrate that as compared with HF-HD, OL-HDF markedly reduces the number of proinflammatory CD14+CD16+ cells and the production of TNF-alpha and IL-6. Future studies are needed to assess the possible therapeutic effect of convective transport on chronic inflammation that is associated with HD.