[Clinical practice guideline for quality control of hemodiafiltration].

This guideline was co-authored by a writing committee of experts in hemodiafiltration. Based on the current evidence-based resources, the guideline drew on and referred to the current relevant clinical practice guidelines and expert recommendations at home and abroad, as well as the Standard Operating Procedures for Blood Purification (2021 Edition), focusing on clinical and medical quality control issues such as the indications for hemodiafiltration, the selection of treatment modes, the selection of replacement fluid and the adjustment of components, vascular access, anticoagulation therapy, prescription setting, and prevention and treatment of related complications. The guideline aimed to guide the clinical practice and clinical research of hemodiafiltration in China, and improve the standardization, normalization and homogeneity of medical quality of hemodiafiltration.

[Risk analysis and validation of the process for producing the substitution fluid for online hemodiafiltration]. / Analyse des risques et validation du procédé de production du liquide de substitution de la technique d'hémodiafiltration en ligne.

INTRODUCTION: Online hemodiafiltration is a technique of dialysis with many advantages, but its use is limited because of the lack of control of microbiological risks. This work conducts a risk analysis of the process for producing substitution liquid for online hemodiafiltration and validates this process from a microbiological point of view. MATERIAL AND METHOD: The risk analysis was carried out following the approach of analysing failure modes, their effects and their criticalities. It identified the "worst case" of the production process being studied. For the validation of this process, we used the limulus amoebocytes lysate assay for bacterial endotoxins and the membrane filtration test for sterility control. RESULTS: We identified 17 failure modes, 13 of which were acceptable. Failure modes that exceeded the acceptability threshold were defined as "worst cases". Sterility monitoring and endotoxin testing, conducted in the "worst case", verified the microbiological quality of the liquid produced to the required standards and subsequently validated the process used. DISCUSSION: This approach has resulted in the identification of as many failure modes as possible. Validating in "worst case" is an extreme challenge to the process and its success provides a sufficient basis to conclude that the technique is safe and, therefore, to validate the process. CONCLUSION: This work has enabled us to validate our production process in extreme cases to promote safer use of the technique.

Is high-volume post-dilution haemodiafiltration associated with risk of fluid volume imbalance? A national multicentre cross-sectional cohort study.

BACKGROUND: Fluid overload is frequent among hemodialysis (HD) patients. Dialysis therapy itself may favor sodium imbalance from sodium dialysate prescription. As on-line hemodiafiltration (OL-HDF) requires large amounts of dialysate infusion, this technique can expose to fluid accumulation in case of a positive sodium gradient between dialysate and plasma. To evaluate this risk, we have analyzed and compared the fluid status of patients treated with HD or OL-HDF in French NephroCare centers. METHOD: This is a cross-sectional and retrospective analysis of prevalent dialysis patients. Data were extracted from the EUCLID5 data base. Patients were split in 2 groups (HD and OL-HDF) and compared as whole group or matched patients for fluid status criteria including predialysis relative fluid overload (RelFO%) status from the BCM®. RESULTS: 2242 patients (age 71 years; female: 39%; vintage: 38 months; Charlson index: 6) were studied. 58% of the cohort were prescribed post-dilution OL-HDF. Comparing the HD and OL-HDF groups, there was no difference between HD and OL-HDF patients regarding the predialysis systolic BP, the interdialytic weight gain, the dialysate-plasma sodium gradient, and the predialysis RelFO%. The stepwise logistic regression did not find dialysis modality (HD or OL-HDF) associated with fluid overload or high predialysis systolic blood pressure. In OL-HDF patients, monthly average convective or weekly infusion volumes per session were not related with the presence of fluid overload. CONCLUSIONS: In this cross-sectional study we did not find association between the use of post-dilution OL-HDF and markers of fluid volume excess. Aligned dialysis fluid sodium concentrations to patient predialysis plasma sodium and regular monitoring of fluid volume status by bioimpedance spectroscopy may have been helpful to manage adequately the fluid status in both OL-HDF and HD patients.

Comparison of Solute Clearance, Hospitalization Rate, and Aortic Arch Calcification between Online Hemodiafiltration and High-Flux Hemodialysis: A 6-Year Observational Study.

BACKGROUND/AIMS: Studies on the long-term clinical benefits of hemodiafiltration (HDF) and high-flux hemodialysis (HFHD) are very limited. This study aimed to investigate the hospitalization rate and aortic arch calcification (AAC) of these two dialysis modalities over 6 years. METHODS: Participants who received regular HDF and HFHD in one hospital-facilitated hemodialysis center were prospectively enrolled after matching for age, sex, and diabetes between January 2009 and December 2014. Medical records were reviewed retrospectively on demographics, laboratory variables, calcified scores in aortic arch measured by chest radiography, and rates of hospital admission. Cox proportional hazard regression and linear regression were used to obtain the outcome results. RESULTS: The HDF and HFHD groups consisted of 108 and 102 participants, respectively. Levels of laboratory variables including small soluble solutes and Kt/V were not statistically different over the 6-year period between the HDF and HFHD groups. Calcified scores of the aortic arch increased over 6 years in both groups. The changes in the mean calcified scores were significant when compared between the two groups (0.44-1.82 in HFHD, 0.79-1.8 in HDF, respectively, p = 0.008). Hospitalization rates were 735 per 1,000 patients in the HDF group and 852 per 1,000 patients in the HFHD group, respectively. No significant difference was observed in frequency and days of hospitalization between HDF and HFHD. CONCLUSION: Hospitalization rates and AAC were observed to be equal for HDF and HFHD.

Clinical evidence on haemodiafiltration.

Haemodiafiltration (HDF) combines diffusive and convective solute removal in a single treatment session. HDF provides a greater removal of higher molecular weight uraemic retention solutes than conventional high-flux haemodialysis (HD). Recently completed randomized clinical trials suggest better patient survival with online HDF. The treatment is mainly used in Europe and Japan. This review gives a brief overview of the presently available evidence of the effects of HDF on clinical end points, it speculates on possible mechanisms of a beneficial effect of HDF as compared with standard HD and ends with some perspectives for the future.

Is There Enough Evidence to Prove That Hemodiafiltration Is Superior?

The evidence concerning online hemodiafiltration (HDF) includes the following: (1) the increase of removal of uremic toxin, (2) the prevention of dialysis rerated hypotension, (3) the recovery of survival, and (4) the recovery of dialysis related uncertain symptoms. Although clinical evidence has been noted, the hypothesis of the efficacy of HDF are still indefinite and require further precise research.

Regulatory Considerations for Hemodiafiltration in the United States.

Online hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis. However, online hemodiafiltration is used sparsely in the United States in part because of a paucity of delivery systems cleared for clinical use by the US Food and Drug Administration. Although a pathway for regulatory approval exists in the United States, concerns remain, particularly regarding online production of the large volumes of sterile, nonpyrogenic substitution fluid infused directly into the bloodstream to maintain fluid balance. Clearly defined testing protocols, acceptable to Food and Drug Administration, will be useful to show that an online hemodiafiltration system is capable of routinely achieving a sterility assurance level of 10-6 and nonpyrogenic levels of endotoxin. Large-scale clinical experience has shown that systems providing this level of performance when combined with certain design features, such as redundancy, and an appropriate quality management process can routinely and safely produce substitution fluid for online hemodiafiltration.

Guía de práctica clínica para la adecuación de hemodiálisis: guía en versión extensa / Clinical practice guide for the adequacy of hemodialysis: guide in extended version

Este documento abarca la adecuación de hemodiálisis.

Current practice in continuous renal replacement therapy: An epidemiological multicenter study. / Manejo actual de las terapias continuas de reemplazo renal: Estudio epidemiológico multicéntrico.

OBJECTIVE: The aim of the study is to ascertain the most relevant aspects of the current management of renal replacement therapy (RRT) in critically ill patients, and to analyze renal function recovery and mortality in patients undergoing RRT. METHODS: A non-interventional three-month observational study was made in 2012, with a follow-up period of 90 days, in 21 centers in Catalonia (Spain). Demographic information, severity scores and clinical data were obtained, as well as RRT parameters. INCLUSION CRITERIA: patients aged ≥ 16 years admitted to Intensive Care Units (ICUs) and subjected to RRT. RESULTS: A total of 261 critically ill patients were recruited, of which 35% had renal dysfunction prior to admission. The main reason for starting RRT was oliguria; the most widely used RRT modality was hemodiafiltration; and the median prescribed dose at baseline was 35mL/kg/h. The median time of RRT onset from ICU admission was one day. The mortality rate at 30 and 90 days was 46% and 54%, respectively, and was associated to greater severity scores and a later onset of RRT. At discharge, 85% of the survivors had recovered renal function. CONCLUSIONS: Current practice in RRT in Catalonia abides with the current clinical practice guidelines. Mortality related to RRT is associated to later onset of such therapy. The renal function recovery rate at hospital discharge was 85% among the patients subjected to RRT.

What Is the Optimal Target Convective Volume in On-Line Hemodiafiltration Therapy?

Conventional diffusion-based dialysis modalities including high-flux hemodialysis are limited in their capacity to effectively remove large uremic toxins and to improve outcomes for end-stage chronic kidney disease (ESKD) patients. By increasing convective solute transport, hemodiafiltration (HDF) enhances solute removal capacity over a broad range of middle- and large-size uremic toxins implicated in the pathophysiology of chronic kidney disease. Furthermore, by offering flexible convection volume, on-line HDF permits customizing the treatment dose to the patient's needs. In addition, convective-based modalities have been shown to improve hemodynamic stability and to reduce patients' inflammation profile - both of which are implicated in CKD morbidity and mortality. Growing clinical evidence indicates that HDF-based modalities provide ESKD patients with a number of clinical and biological benefits, including improved outcomes. Interestingly, it has recently emerged that the clinical benefits associated with HDF are positively associated with the total ultrafiltered volume per session (and per week), namely convective dose. In this chapter, we revisit the concept of convective dose and discuss the threshold value above which an improvement in ESKD patient outcome can be expected. This particular point will be addressed by stratifying the level of efficacy of convective volumes, schematically defined as minimal, optimal, personalized, and maximal. In addition, factors and best clinical practices implicated in the achievement of an optimal convective dose are reviewed. To conclude, we show how HDF differs from standard hemodialysis and why HDF offers a paradigm shift in renal replacement therapy.

Clinical Effectiveness of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared with Predilution On-Line Hemodiafiltration.

BACKGROUND: In conventional hemodialysis (HD) treatment, excessive water removal sometimes induces a rapid drop in blood pressure. Intermittent infusion hemodiafiltration (I-HDF) has been developed to improve patients' peripheral circulation by repeated intermittent infusion during HD treatment. SUMMARY: A prospective, multicenter, parallel group comparative trial examined the clinical effectiveness of I-HDF compared with predilution on-line HDF (pre-HDF), the most popular on-line HDF therapy in Japan. Patients were allocated to 2 groups after matching for age (± 5 years), dry weight (± 5 kg), and presence/absence of diabetes. After informed consent was obtained, 36 patients (18 pairs) participated in the trial. The results showed no difference in clinical condition or quality of life (QOL) scores between the 2 therapy groups. The rate of reduction in systolic blood pressure initially showed no difference between the groups, but decreased slightly as the trial proceeded after changing from HD therapy. There was also no difference in the incidence rate of treatments initially, although this significantly decreased in both groups as the trial proceeded. Rates of ß2-microglobulin removal were significantly higher in the pre-HDF group than in the I-HDF group. At the same time, the amount of albumin leakage during treatment was significantly greater in the pre-HDF group. Key Messages: The clinical condition and QOL of patients receiving I-HDF was not inferior to those receiving pre-HDF. Pre-HDF demonstrated a significantly higher removal rate of middle- and larger-molecular-weight solutes and higher albumin leakage compared with I-HDF.

Biocompatibility of Hemodiafilters.

BACKGROUND: Biocompatibility and the efficiency of solute removal are important considerations in blood purification therapy. Improvement of biocompatibility is expected to lead to the prevention of dialysis-related complications (e.g. amyloidosis, arteriosclerosis, and malnutrition) and to the delay of disease progression by alleviating microinflammation. SUMMARY: The biocompatibility of dialyzers is greatly influenced by the interaction between blood and the treatment materials, in which the chemical and physical characteristics of membrane materials play important roles. In hemodiafiltration (HDF), treatment characteristics such as dilution modes are also considered to greatly affect this interaction between blood and materials. Studies have reported that the levels of C-reactive protein are decreased in patients receiving HDF. Thus, the improvement of biocompatibility is an important factor in HDF. Key Messages: To improve the biocompatibility of HDF, it is essential to improve the biocompatibility of hemodiafilters. This article outlines the importance of biocompatibility and related factors in HDF.

A New Poly(Methyl Methacrylate) Membrane Dialyzer, NF, with Adsorptive and Antithrombotic Properties.

BACKGROUND: Poly(methyl methacrylate) (PMMA) membranes adsorb several kinds of proteins and can remove high-molecular-weight proteins, including uremic toxins, which are not removed efficiently by hemodialysis or hemodiafiltration. However, the antithrombogenicity of PMMA membranes is insufficient due to their adsorptive properties. SUMMARY: Coagulation during hemodialysis occurs because proteins that are adsorbed to the PMMA membrane undergo structural changes and are recognized by platelets, which are then activated by adhesion to the membrane surface. In developing a new PMMA membrane dialyzer, NF, we intended to inhibit platelet adhesion to the membrane surface by suppressing the structural change in the proteins adsorbed on the membrane. In addition, we give examples of clinical trials of the NF in Japan and describe its advantages. Key Message: PMMA membrane dialyzers have been used for 40 years. The PMMA dialyzer NF can suppress the adhesion of platelets to the membrane while maintaining protein adsorption.

Ultrafiltration Rates and the Quality Incentive Program: Proposed Measure Definitions and Their Potential Dialysis Facility Implications.

BACKGROUND AND OBJECTIVES: Rapid ultrafiltration rates are associated with adverse outcomes among patients on hemodialysis. The Centers for Medicare and Medicaid Services is considering an ultrafiltration rate quality measure for the ESRD Quality Incentive Program. Two measure developers proposed ultrafiltration rate measures with different selection criteria and specifications. We aimed to compare the proposed ultrafiltration rate measures and quantify dialysis facility operational burden if treatment times were extended to lower ultrafiltration rates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were taken from the 2012 database of a large dialysis organization. Analyses of the Centers for Medicare and Medicaid Services measure considered 148,950 patients on hemodialysis, and analyses of the Kidney Care Quality Alliance measure considered 151,937 patients. We described monthly patient and facility ultrafiltration rates and examined differences in patient characteristics across ultrafiltration rate thresholds and differences in facilities across ultrafiltration rate measure scores. We computed the additional treatment time required to lower ultrafiltration rates <13 ml/h per kilogram. RESULTS: Ultrafiltration rates peaked in winter and nadired in summer. Patients with higher ultrafiltration rates were younger; more likely to be women, nonblack, Hispanic, and lighter in weight; and more likely to have histories of heart failure compared with patients with lower ultrafiltration rates. Facilities had, on average, 20.8%±10.3% (July) to 22.8%±10.6% (February) of patients with ultrafiltration rates >13 ml/h per kilogram by the Centers for Medicare and Medicaid Services monthly measure. Facilities had, on average, 15.8%±8.2% of patients with ultrafiltration rates ≥13 ml/h per kilogram by the Kidney Care Quality Alliance annual measure. Larger facilities (>100 patients) would require, on average, 33 additional treatment hours per week to lower all facility ultrafiltration rates <13 ml/h per kilogram when total treatment time is capped at 4 hours. CONCLUSIONS: Ultrafiltration rates vary seasonally and across clinical subgroups. Extension of treatment time as a strategy to lower ultrafiltration rates may pose facility operational challenges. Prospective studies of ultrafiltration rate threshold implementation are needed.

Efficacy of Two Combinations of Blood Purification Techniques for the Treatment of Multiple Organ Failure Induced by Wasp Stings.

BACKGROUND/AIMS: The aim of this study was to explore the clinical efficacy of 2 combinations of blood purification techniques in patients with sting venom-induced multiple organ dysfunction syndrome (MODS). METHODS: A total of 23 patients received 35 sessions of hemoperfusion (HP) + continuous veno-venous hemodiafiltration (CVVHDF) treatment and 22 sessions of plasma exchange (PE) + CVVHDF treatment, respectively. RESULTS: Both HP + CVVHDF and PE + CVVHDF reduced the levels of inflammation, thus improving our patients' health condition. Moreover, PE + CVVHDF was found to be significantly more effective in reducing the levels of specific liver function markers and inflammatory mediators, as well as shortening prothrombin time and increasing the levels of serum albumin. CONCLUSION: Both combinations of blood purification techniques were capable of improving MODS. However, the PE + CVVHDF approach was more efficient for the removal of wasp venom and inflammatory mediators from the blood.

Compliance with guidelines and predictors of mortality in hemodialysis. Learning from Serbia patients.

OBJECTIVES: The aims of the study were to determine the percentage of patients on regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and find out factors associated with the risk of time to death and the association between guidelines adherence and patient outcome. METHODS: A cohort of 2153 patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia were followed from January 2010 to December 2012. The percentage of patients failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin (>110g/L), serum phosphorus (1.1-1.8mmol/L), calcium (2.1-2.4mmol/L) and iPTH (150-300pg/mL) was determined. Cox proportional hazards analysis was used to select variables significantly associated with the risk of time to death. RESULTS: The patients were on regular HD for 5.3±5.3 years, dialyzed 11.8±1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s-phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had 11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of patients. Using Cox model (adjustment for patient age, gender, duration of HD treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic nephropathy were selected as significant independent predictors of time to death. When targets of five examined parameters were included in Cox model, target for KtV, hemoglobin and iPTH were found to be significant independent predictors of time to death. CONCLUSION: Substantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.

Mathematical Modeling of Different Molecule Removal on On-Line Haemodiafiltration: Influence of Dialysis Duration and Infusion Flow.

BACKGROUND: In a previous study on a nocturnal, every-other-day online haemodiafiltration scheme, different removal patterns were observed for urea, creatinine, ß2-​microglobulin, myoglobin and prolactin. The aim of this study was to evaluate the influence of dialysis duration and infusion flow (Qi) on the removal of different molecular weight (MW) solutes, and to quantify the effect of the different treatments on the kinetics of the solutes by using a classical two-compartment model. METHODS: This prospective, in-center study was carried out in 10 patients on a nocturnal, every-other-day online post-dilution haemodiafiltration program. Each patient received four dialysis sessions with different conditions, two 4-h sessions (with infusion flows of 50 or 100 ml/min) and two 8-h sessions (with infusion flows of 50 or 100 ml/min). To analyze the solute kinetics, blood samples were obtained hourly during the dialysis treatments and in the first 3 h post-dialysis. RESULTS: Removal patterns differed in the molecules studied, which were quantified by means of the two-compartment mathematical model. The main results show the impact of dialysis duration on the removal of low molecular weight molecules (urea and creatinine), while the impact of Qi is clearly shown for high molecular weight molecules (myoglobin and prolactin). For middle molecular weight solutes, such as ß2-microglobulin, both factors (duration and Qi) enhance the removal efficiency of the dialyzer. CONCLUSIONS: Our study evaluates experimentally and mathematically how treatment time and infusion flow affect the filtration of solutes of different MW during post-dilution haemodiafiltration. The results provided by the present study should help physicians to select and individualise the most appropriate schedules to deliver an optimum diffusive and convective dialysis dose for each patient.

[Kidney diseases in cardiology]. / Choroby nerek w kardiologii.

A close relationship between renal dysfunction and heart failure has been demonstrated with a huge impact on the patients outcomes. To describe the relationship, the term cardio-renal syndrome (CRS) has been increasingly used in recent years. Medical management of patients with CRS remains tremendously challenging. The integration of cardiology and nephrology communities providing with a more holistic and complete clinical presentation of patients seems to be a necessary strategy to treat this vulnerable population.