Effect of centre- and patient-related factors on uptake of haemodiafiltration in Australia and New Zealand: A cohort study using ANZDATA.

BACKGROUND: The use of haemodiafiltration (HDF) for the management of patients with end-stage kidney failure is increasing worldwide. Factors associated with HDF use have not been studied and may vary in different countries and jurisdictions. The aim of this study was to document the pattern of increase and variability in uptake of HDF in Australia and New Zealand, and to describe patient- and centre-related factors associated with its use. METHODS: Using the Australian and New Zealand Dialysis and Transplant Registry, all incident patients commencing haemodialysis (HD) between 2000 and 2014 were included. The primary outcome was HDF commencement over time, which was evaluated using multivariable logistic regression stratified by country. RESULTS: Of 27 433 patients starting HD, 3339 (14.4%) of 23 194 patients in Australia and 810 (19.1%) of 4239 in New Zealand received HDF. HDF uptake increased over time in both countries but was more rapid in New Zealand than Australia. In Australia, HDF use was more likely in males (odds ratio (OR) 1.13, 95% confidence interval (CI) = 1.03-1.24, P = 0.009) and less likely with older age (reference <40 years; 40-54 years OR = 0.85; 95% CI = 0.72-0.99; 55-69 years OR = 0.79; 95% CI = 0.67-0.91; >70 years OR = 0.48; 95% CI = 0.41-0.56); higher body mass index (body mass index (BMI) < 18.5 kg/m2 OR = 0.62; 95% CI = 0.46-0.84; 18.5-29.9 kg/m2 reference; >30 kg/m2 OR = 1.46; 95% CI = 1.33-1.61), chronic lung disease (OR = 0.84; 95% CI = 0.76-0.94; P < 0.001), cerebrovascular disease (OR = 0.76; 95% CI = 0.67-0.85; P < 0.001) and peripheral vascular disease (OR = 0.77; 95% CI = 0.70-0.85; P < 0.001). No association was identified with race. In New Zealand, HDF use was more likely in Maori and Pacific Islanders (OR = 1.32; 95% CI = 1.05-1.66) and Asians (OR = 1.75; 95% CI = 1.15-2.68) compared to Caucasians, and less likely in males (OR = 0.76; 95% CI = 0.62-0.94; P = 0.01). No association was identified with BMI or co-morbidities. In both countries, centres with a higher ratio of HD to peritoneal dialysis (PD) were more likely to prescribe HDF. Larger Australian centres were more likely to prescribe HDF (36-147 new patients/year OR = 26.75, 95% CI = 18.54-38.59; 17-35/year OR = 7.51, 95% CI = 5.35-10.55; 7-16/year OR = 3.00; 95% CI = 2.19-4.13; ≤6/year reference). CONCLUSION: Haemodiafiltration uptake is increasing, variable and associated with both patient and centre characteristics. Centre characteristics not explicitly captured elsewhere explained 36% of variability in HDF uptake in Australia and 48% in New Zealand.

Design and methodology of the impact of HemoDiaFIlTration on physical activity and self-reported outcomes: a randomized controlled trial (HDFIT trial) in Brazil.

BACKGROUND: End stage renal disease (ESRD) patients require a renal replacement therapy (RRT) to filter accumulated toxins and remove excess water, which are associated with impaired physical function. Hemodialysis (HD) removes middle-molecular weight (MMW) toxins less efficiently compared to hemodiafiltration (HDF); we hypothesized HDF may improve physical function. We detailed the design and methodology of the HDFIT protocol that is testing whether changing from HD to HDF effects physical activity levels and various outcomes. METHODS: HDFIT is a prospective, multi-center, unblinded, randomized control trial (RCT) investigating the impact of dialysis modality (HDF verses HD) on objectively measured physical activity levels, self-reported quality of life, and clinical/non-clinical outcomes. Clinically stable patients with HD vintage of 3 to 24 months without any severe limitation ambulation were recruited from sites throughout southern Brazil. Eligible patients were randomized in a 1:1 ratio to either: 1) be treated with high volume online HDF for 6 months, or 2) continue being treated with high-flux HD. This study includes run-in and randomization visits (baseline), 3- and 6-month study visits during the interventional period, and a 12-month observational follow up. The primary outcome is the difference in the change in steps per 24 h on dialysis days from baseline to the 6-month follow up in patients treated with HDF versus HD. Physical activity is being measured over one week at study visits with the ActiGraph ( www.actigraphcorp.com ). For assessment of peridialytic differences during the dialysis recovery period, we will analyze granular physical activity levels based on the initiation time of HD on dialysis days, or concurrent times on non-dialysis days and the long interdialytic day. DISCUSSION: In this manuscript, we provide detailed information about the HDFIT study design and methodology. This trial will provide novel insights into peridialytic profiles of physical activity and various self-reported, clinical and laboratory outcomes in ESRD patients treated by high volume online HDF versus high-flux HD. Ultimately, this investigation will elucidate whether HDF is associated with patients having better vitality and quality of life, and less negative outcomes as compared to HD. TRIAL REGISTRATION: Registered on ClinicalTrials.gov on 20 April 2016 ( NCT02787161 ).

Effect of haemodiafiltration vs conventional haemodialysis on growth and cardiovascular outcomes in children - the HDF, heart and height (3H) study.

BACKGROUND: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population. METHODS: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m2; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38). DISCUSSION: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.

Una nueva generación de triacetato de celulosa adecuado para hemodiafiltración on-line / A new generation of cellulose triacetate suitable for online haemodiafiltration

Antecedentes: La hemodiafiltración on-line (HDF-OL) es actualmente la técnica de hemodiálisis (HD) más efectiva y aumenta la supervivencia. Hasta el momento presente las membranas de alta permeabilidad con baja pérdida de albúmina como las de polisulfona, poliamida y poliacrilonitrilo son las más utilizadas. Las membranas de triacetato de celulosa (TAC), limitadas inicialmente para su uso en HDF-OL, han evolucionado. El objetivo del estudio fue determinar si las membranas de nueva generación de TAC asimétrico (TACA) son más adecuadas para realizar alto transporte convectivo. Pacientes y métodos: Se estudiaron 16 pacientes, 10 hombres y 6 mujeres, en programa de HDF-OL. A cada paciente se le realizaron 4 sesiones diferentes, con HD o HDF-OL, o con filtros de TAC o TACA de 1,9 m2, aleatorizando el orden. En cada sesión se determinaron concentración de urea, creatinina, β2-microglobulina, mioglobina, prolactina, α1-microglobulina, α1-glicoproteína ácida y albúmina en suero al inicio y al final de cada sesión, para calcular el porcentaje de reducción. Así mismo, se cuantificó la pérdida de solutos y albúmina en el líquido de diálisis. Resultados: Con las membranas de TACA se consiguió un volumen de sustitución en HDF-OL significativamente superior a las membranas de TAC clásicas (32,1±3,1 vs. 19,7±4,5L; p<0,001). En términos de depuración, la eliminación de moléculas pequeñas fue similar con ambas membranas, pero, en moléculas grandes, con HDF-OL la depuración fue mayor con TACA. En HDF-OL, el porcentaje de reducción de la β2-microglobulina se incrementó un 29%, un 27,7% la mioglobina, un 19,5% la prolactina, un 49% la α1-microglobulina, y se duplicó la α1-glicoproteína ácida (p<0,01 en todas las situaciones). La pérdida de albúmina fue inferior a 2 g en todas las situaciones de estudio. Conclusión: Las membranas de TAC de nueva generación han demostrado ser eficaces para alcanzar los objetivos de HDF-OL, sin que haya una mayor pérdida de albúmina (AU)

Background: Online haemodiafiltration (OL-HDF) is currently the most effective dialysis technique that also improves survival. To date, high permeability membranes with low albumin loss, such as polysulfone, polyamide and polyacrylonitrile membranes have been the most widely used. However, the initially restricted use of cellulose triacetate (CTA) membranes in OL-HDF has expanded. The aim of the study was to ascertain whether the latest generation asymmetric CTA membranes are more effective in obtaining high convective transport. Patients and methods: A total of 16 patients (10 males and 6 females) undergoing OL-HDF were studied. Each patient underwent 4 different sessions, with haemodialysis or OL-HDF, and/or with CTA or asymmetric CTA 1.9 m2 membranes. Each session was assigned in a randomised order. Serum levels of urea, creatinine, β2-microglobulin, myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein and albumin where measured at the beginning and end of each session to obtain the reduction rate. The loss of solutes and albumin was quantified from the dialysate. Results: A significantly greater replacement volume in OL-HDF (32.1±3.1 vs. 19.7±4.5 l, P<.001) was obtained by using asymmetrical CTA membranes compared to conventional CTA membranes. Regarding uraemic toxin removal, both membranes obtained similar results for small molecules, whereas asymmetric CTA membranes achieved better results for large molecules, increasing the reduction ratio by 29% for β2-microglobulin, 27.7% for myoglobin, 19.5% for prolactin, 49% for α1-microglobulin and double for α1-acid glycoprotein (P<0.001 in all situations). The loss of albumin was less than 2g for all treatment sessions. Conclusion: Latest-generation asymmetric CTA have proven to be effective in attaining OL-HDF objectives without increased albumin loss (AU)

On-line hemodiafiltration did not induce an overproduction of oxidative stress and inflammatory cytokines in intensive care unit-acute kidney injury.

BACKGROUND: Though on-line intermittent hemodiafiltration (OL-IHDF) is a routine therapy for chronic dialysis patients, it is not yet widespread used in critically ill patients. This study was undergone to evaluate efficiency and tolerance of OL-IHDF and to appreciate inflammatory consequences of its use in intensive care unit (ICU)-acute kidney injury (AKI) patients. METHODS: In this prospective cohort study conducted in a medical academic ICU in France, 30 AKI patients who underwent OL-IHDF were included. OL-HDF used an ultrapure water production: AQ 1250 line with double reverse osmosis, a generator 5008 with a 1.8m2 dialyzer with Polysulfone membrane (Fresenius Medical Care). Tolerance and efficiency of OL-IHDF were evaluated as well as its inflammatory risk by the measurement of plasma concentrations of proinflammatory (Interleukin 6, IL1ß, IL8, Interferon γ) and anti-inflammatory (IL4, IL10) cytokines, Epidermal growth factor (EGF), Vascular Endothelial growth factor (VEGF) and Macrophage Chemoattractive Protein-1 (MCP-1) before and after sessions. RESULTS: Intradialytic hypotensive events were observed during 27/203 OL-IHDF sessions accounting for a mal-tolerated session's rate at 13.3%. Mean delivered urea Kt/V per session was 1.12 ± 0.27 with a percentage of reduction for urea, creatinine, ß2-microglobulin and cystatine C at 61.6 ± 8.8%, 55.3 ± 6.7%, 51.5 ± 8.7% and 44.5 ± 9.8% respectively. Production of superoxide anion by leukocytes, mean levels of pro- and anti-inflammatory cytokines and plasmatic concentrations of EGF, VEGF and MCP-1 did not differ before and after OL-IHDF sessions. We observed however a significant decrease of mean TNFα plasmatic concentrations from 8.2 ± 5.8 to 4.8 ± 3.5 pg/ml at the end of OL-IHDF. CONCLUSIONS: OL-IHDF was not associated with an increase in pro and anti-inflammatory cytokines, oxidative stress or EGF, VEGF and MCP-1 in AKI patients and seems therefore a secure and feasible modality in ICUs.

Peritoneal dialysis for the management of pediatric patients with acute kidney injury.

Renal replacement therapy (RRT) is the most important supportive measure used in the management of acute kidney injury (AKI). Peritoneal dialysis (PD) is a safe, simple and inexpensive procedure and has been used in pediatric AKI patients, ranging from neonates to adolescents. It is the modality of choice for RRT in developing countries with cost constraints and limited resources. However, its use has declined with the availability of newer types of extracorporeal modalities for RRT in the developed world. Much controversy exists regarding the dosing and adequacy of PD in the management of AKI. Data in infants and children have shown that PD can provide adequate clearance, ultrafiltration and correction of metabolic abnormalities even in those who are critically ill. Although there are no prospective studies in children, data from retrospective studies reveal no differences in mortality rates between different modalities of RRT. In this review, we discuss the advantages and limitations of PD, indications for acute PD, strategies to improve the efficiency of acute PD and outcomes of PD in children with AKI.

Caspofungin Population Pharmacokinetics in Critically Ill Patients Undergoing Continuous Veno-Venous Haemofiltration or Haemodiafiltration.

BACKGROUND AND OBJECTIVE: Sepsis and continuous renal replacement therapy (CRRT) can both significantly affect antifungal pharmacokinetics. This study aimed to describe the pharmacokinetics of caspofungin in critically ill patients during different CRRT modes. METHODS: Patients receiving caspofungin and undergoing continuous veno-venous haemofiltration (CVVH) or haemodiafiltration (CVVHDF) were eligible to take part in the study. Blood samples were collected at seven sampling times during a dosing interval. Demographics and clinical data were recorded. Population pharmacokinetic analysis and Monte-Carlo simulation were undertaken using Pmetrics. RESULTS: Twelve pharmacokinetic profiles from nine patients were analysed. The caspofungin CRRT clearance (CL) was 0.048 ± 0.12 L/h for CVVH and 0.042 ± 0.042 L/h for CVVHDF. A two-compartment linear model best described the data. Patient weight was the only covariate affecting drug CL and central volume. The mean (standard deviation) parameter estimates were 0.64 ± 0.12 L/h for CL, 9.35 ± 3.56 L for central volume, 0.25 ± 0.19 per h for the rate constant for drug distribution from central to peripheral compartments and 0.19 ± 0.10 per h from peripheral to central compartments. Based on simulation results, a caspofungin 100 mg loading dose followed by a 50 mg maintenance dose for patients with a total body weight of ≤80 kg best achieved the pharmacokinetic/PD targets whilst a 70 mg maintenance dose was required for patients with a weight of >80 kg. CONCLUSION: No caspofungin dosing adjustment is necessary for patients undergoing either form of CRRT. However, higher than recommended loading doses of caspofungin are required to achieve pharmacokinetic/pharmacodynamic targets in critically ill patients. Registration: ClinicalTrials.gov Identifier NCT01403220.

Evolution of Technology for Continuous Renal Replacement Therapy: Forty Years of Improvements.

Continuous arteriovenous hemofiltration (CAVH) was proposed in 1977 as an alternative treatment for acute renal failure in patients in whom peritoneal dialysis or hemodialysis was clinically or technically precluded. In the mid-1980s, this technique was extended to infants and children. CAVH presented important advantages in the areas of hemodynamic stability, control of circulating volume, and nutritional support. However, there were serious shortcomings such as the need for arterial cannulation and limited solute clearance. These problems were solved by the introduction of continuous arteriovenous hemodiafiltration (CAVHDF) and continuous arteriovenous hemodialysis (CAVHD) where uremic control could be by increasing countercurrent dialysate flow rates to 1.5 or 2 liters/h as necessary, or by venovenous techniques utilizing a double-lumen central venous catheter for vascular access. Thus, continuous venovenous hemofiltration replaced CAVH because of its improved performance and safety. From the initial adoptive technology, specific machines have been designed to permit safe and reliable performance of the therapy. These new machines have progressively undergone a series of technological steps that have resulted in the highly sophisticated equipment utilized today. A significant number of advances have taken place since the beginning of continuous renal replacement therapy. In particular, there have been successful experiments with high-volume hemofiltration and high-permeability hemofiltration. The additional and combined use of sorbent has also been tested successfully. Progress has been made in the technology as well as the understanding of the pathophysiology of acute kidney injury. Today, new biomaterials and new devices are available and new frontiers are on the horizon. Although improvements have been made, a lot remains to be done. Critical care nephrology is expected to further evolve in the near future, especially in the area of information and communication technology, utilization of big data and large database registries, biofeedback, and assisted prescription and treatment delivery, with high potential for improvement in morbidity and mortality of the most severely ill patients.

Líquido dializante con citrato frente a acetato en pacientes en hemodiafiltración on-line de alta eficacia: parámetros a estudio / Citrate- versus acetate- based dialysate in patients in high-efficiency online hemodiafiltration: parameters to be studied

Introducción: El líquido dializante con acetato se reporta menos biocompatible, generando estrés oxidativo e inflamación. Entre los beneficios asociados al citrato destacan sus propiedades antiinflamatorias y antioxidantes, poder anticoagulante, quelante del calcio iónico, efecto tampón y mejora la tolerancia a la sesión. Objetivo: Comparar parámetros nutricionales e inflamatorios, eficacia dialítica, estatus ácido-base, tolerancia y balance de calcio en hemodiafiltración en línea empleando líquido dializante con citrato frente a líquido dializante con acetato. Material y métodos: Estudio prospectivo cruzado sobre población en hemodiafiltración en línea de 24 semanas. Inician 35 pacientes (finalizan 33), con 57,4 años, 55% hombres, 54,1 meses de permanencia. 79% portadores de fistula arteriovenosa. Se analizan 2376 sesiones. El estudio tiene dos fases. Variables: albúmina, PCR, Beta 2 microglobulinas (B2MCG), ángulo de fase (AF), masa celular corporal (BCM), Kt, volumen de reinfusión, PTTA, tiempo de hemostasia, estado de cámaras y dializador, pH, bicarbonato, calcio iónico, sesiones con hipotensión y calambres. Análisis estadístico SPSS 13.0. Contraste de hipótesis mediante T-Student y W de Wilcoxon para variables cuantitativas. Chi-cuadrado cualitativas. Significación estadística p<0,05. Resultados: Diferencias significativas (p<0,001) en albúmina, PCR, y B2MCG. BCM (p=0,001), AF (p=0,002) y Kt (p< 0,001) mayores con líquido de diálisis con citrato. Bicarbonato postdiálisis menor (p<0,001) con líquido de diálisis con citrato. Calcio iónico pre y postdiálisis (p=0,007 y p<0,001 respectivamente) menores con líquido de diálisis con citrato. Conclusiones: La diálisis con citrato se muestra en nuestra serie más biocompatible y con menor inflamación, mejora los parámetros nutricionales analíticos y por impedancia e incrementa la eficacia dialítica. Reduce el bicarbonato postdiálisis. Tanto pre como postdiálisis el calcio iónico es menor, permaneciendo estable (AU)

Introduction: Liquid dialysate with acetate (LDA) reported less biocompatible, generating oxidative stress and inflammation. Perceived benefits include its anti-inflammatory citrate buffer effect and antioxidant properties, anticoagulant power, chelating ionized calcium, and improves tolerance to the session. Objective: To compare nutritional and inflammatory parameters, dialysis efficiency, acid-base status, tolerance and calcium balance in on-line hemodiafiltration (OL-HDF) using citrate dialysate (LDC) versus LDA. Methods: Prospective cross OLHDF population in 24 weeks. Begins 35 patients (33 finish), with 57.4 years, 55% male, 54.1 months of permanence. 79% carriers arteriovenous fistula. 2376 sessions are analyzed. The study has two phases. Variables: albumin, CRP, Beta 2 microglobulin (B2MCG), phase angle (PA), body cell mass (BCM), Kt, reinfusion volume, PTTA, hemostasis time, state cameras and dialyzer, pH, bicarbonate, calcium ion, sessions with hypotension and cramps. Statistical analysis SPSS 13.0. Hypothesis testing using T-Student and Wilcoxon W for quantitative variables. Chi-squared qualitative. Statistical significance p <0.05. Results: Significant differences (p <0.001) in albumin, CRP, and B2MCG. BCM (p = 0.001), AF (p = 0.002) and Kt (p <0.001) higher with LDC. Lower post-dialysis bicarbonate (p <0.001) with LDC. Calcium ion pre and post-dialysis (p = 0.007 and p <0.001 respectively) with lower LDC. Conclusion: Dialysis citrate shown in our series more biocompatible and less inflammation, improves nutritional parameters and analytical impedance and increases efficiency dialysis. Reduces post-dialysis bicarbonate. Both pre-and post-dialysis ionized calcium is lower, remaining sta (AU)

Worsening renal function in patients with acute decompensated heart failure treated with ultrafiltration: predictors and outcomes.

BACKGROUND: Ultrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure(WRF) on mortality in patients treated with UF. METHODS AND RESULTS: Based on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 0.7 to 1.2 ± 1.0 mg/dL (P!.001),and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 75 vs 144 ± 52 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17-13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48-48.42; P = .03), and E/E0 ≥ 15 (OR 3.78, 95% CI 1.26-17.55; P 5 .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60mg/dL who developed WRF during UF had a 75% 1-year mortality rate. CONCLUSIONS: WRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.

Acute hemodynamic response and uremic toxin removal in conventional and extended hemodialysis and hemodiafiltration: a randomized crossover study.

BACKGROUND: Intensive hemodialysis (HD) may have significant benefits. Recently, the role of extended hemodiafiltration (HDF) has gained interest. The aim of this study was to evaluate the acute effects of extended HD and HDF on hemodynamic response and solute removal. STUDY DESIGN: Randomized crossover trial. SETTINGS & PARTICIPANTS: Stable patients with end-stage renal disease undergoing conventional HD. INTERVENTION: 13 patients randomly completed a single study of 4-hour HD (HD4), 4-hour HDF (HDF4), 8-hour HD (HD8), and 8-hour HDF (HDF8), with a 2-week interval between study sessions. Between study sessions, patients received routine conventional HD treatments. OUTCOMES: Acute hemodynamic effects and uremic toxin clearance. MEASUREMENTS: Blood pressure and heart rate, pulse wave analysis, cardiac output, and microvascular density by sublingual capillaroscopy, as well as relative blood volume and thermal variables, were measured. Clearance and removal of uremic toxins also were studied. RESULTS: Long treatments showed more stability of peripheral systolic blood pressure (change during HD4, -21.7±15.6 mm Hg; during HDF4, -23.3±20.8 mm Hg; during HD8, -6.7±15.2 mm Hg [P=0.04 vs. HD4; P=0.08 vs. HDF4]; and during HDF8, -0.5±14.4 mm Hg [P=0.004 vs. HD4; P=0.008 vs. HDF4]). A similar observation was found for peripheral diastolic and central blood pressures. Cardiac output remained more stable in extended sessions (change during HD4, -1.4±1.5 L/min; during HDF4, -1.6±1.0 L/min; during HD8, -0.4±0.9 L/min [P=0.02 vs. HDF4]; and during HDF8, -0.5±0.8 L/min [P=0.06 vs. HD4; P=0.03 vs. HDF4), in line with the decreased relative blood volume slope in long dialysis. No differences in microvascular density were found. Energy transfer rates were comparable (HD4, 13.3±4.7 W; HDF4, 16.2±5.6 W; HD8, 14.2±6.0 W; and HDF8, 14.5±4.3 W). Small-molecule and phosphate removal were superior during long treatments. ß2-Microglobulin and fibroblast growth factor 23 (FGF-23) reduction ratios were highest in HDF8. LIMITATIONS: Small sample size, only acute effects were studied. CONCLUSIONS: Treatment time, and not modality, was the determinant for the hemodynamic response. HDF significantly improved removal of middle molecules, with superior results in extended HDF.

Estudio comparativo en pacientes en Hemodiafiltración en línea postdilucional de alta eficacia con diferentes flujos de líquido dializante, tiempo programado y tiempo real / Comparative study on patients treated with post-dilution on-line haemodiafi ltration, different fl ow rates of dialysis fluid, real dialysis time and prescribed time

La dosis de diálisis es un elemento fundamental en la diálisis adecuada y en la supervivencia del paciente. Entre los elementos que influyen en la misma destacan: tiempo, flujo sanguíneo (Qb), coeficiente de transferencia de masa de urea (KoA) y flujo del baño (Qd). El objetivo es evaluar si con Qd 800 ml/ min y tiempo programado 240 minutos conseguimos mayor eficacia que con Qd 500 ml/min y tiempo programado 240 minutos y con Qd 500 l/min y tiempo efectivo 240 minutos. Pacientes y métodos Estudio prospectivo sobre población prevalente en hemodiálisis, con criterio de inclusión pacientes mayores de edad en hemodiafiltración on-line postdilucional con flujo sanguíneo adecuado. En cada paciente se realizan 18 sesiones consecutivas variando Qd y tiempo con siguiente esquema: Fase 1: 6 sesiones con Qd 800 ml/min y tiempo programado 240 minutos. Fase 2: 6 sesiones con Qd 500 ml/min y tiempo programado 240 minutos, Fase 3: 6 sesiones con Qd 500 ml/min y tiempo efectivo 240 minutos. El análisis estadístico se realiza mediante SPSS 13.0 para Windows. Las variables cuantitativas se expresan como media, desviación estándar y rango. Las variables cualitativas, como frecuencia y porcentaje. Resultados Analizamos 432 sesiones obteniendo Kt y Volumen total de reinfusión (VTR) mayores en la fase 3 del estudio con respecto a las otras dos, no existiendo diferencias significativas entre la fase 1 y 2. Discusión y conclusiones No existen diferencias en la eficacia dialítica entre Qd 500 ml/min y Qd 800 ml/min, mientras que con el aumento de 10 minutos de media en cada sesión, se incrementa la dosis de diálisis en 2,77 litros y el VTR en un 9%, reduciendo a la mitad el número de pacientes que no logran los 20 litros de volumen de reinfusión. Y esto, con un menor coste adicional especialmente por las diferencias de envasado del bicarbonato (AU)

The dialysis dose (DD) is a key element of dialysis adequacy and affects survival of patients undergoing dialysis. Some elements standing out concerning the DD are: dialysis time, blood flow rate (Qb), transfer area coefficient (KOA) and dialysate flow rate (Qd). The aim of this study is to find out whether Qd 800 ml / min and 240 minutes prescribed time is more effective than Qd 500 ml / min and 240 minutes prescribed time and also to compare Qd 500 ml/min and 240 minutes of real dialysis time. Patients and Methods. A transversal prospective study was conducted of a population in dialysis, inclusion criteria being an adult treated with post-dilution on-line haemodiafiltration and sufficient blood flow rate. In all patients was performed 18 consecutive sessions varying Qd and time as follows: Stage 1: 6 sessions Qd 800 ml/min and prescribed time 240 minutes (F1) Stage 2: 6 sessions Qd 500 ml/min and prescribed time 240 minutes (F2) Stage 3: 6 sessions Qd 500 ml/min and real dialysis time 240 minutes (F3) Statistical analysis performed using SPSS 13.0 for Windows. Quantitative variables were expressed as mean, standard deviation and range, and qualitative variables expressed as frequency and percentage. Results 432 sessions analysed getting higher Kt and reinfusion volume (VTR) in stage 3 in relation to other stages. No significant difference between stage 1 and 2. Discussion and conclusions: No differences in dialysis efficacy Qd 500 ml / min versus Qd 800 ml / min. Nevertheless, increasing 10 minutes in each session, the dialysis dose increases 2.77 litres and VTR increases 9%, halving this way the number of patients that don’t reach 20 litres reinfusion volume. All this achieved with a lower fee due to the size difference bicarbonate concentrate packaging(AU)

Development of hemodiafiltration therapy--a historical perspective.

Hemodiafiltration (HDF) was created in the late 1970s to combine the best of hemodialysis (HD) and hemofiltration, i.e. superior removal of both small and large solutes. Thus, optimal conditions for both diffusion and convection are required. The need for large volumes of sterile fluid has shaped the evolution of HDF, and regulatory issues around systems for on-line fluid preparation have delayed the clinical development of the therapy. Not until such systems became generally available in the mid-1990 s was it possible to increase the efficiency of HDF therapy to match and exceed the upgrade that had taken place for HD. Results from recent studies indicate that the potential for improving the outcome of dialysis lies in increasing the convective clearance of HDF above that of high-flux HD.

Estudio comparativo de biocompatibilidad entre la hemodiafiltración en línea y la hemodiafiltración con reinfusión endógena / Biocompatibility comparative study between online hemodiafiltration and hemodiafiltration with endogenous reinfusion

Objetivo: Comparar la biocompatibilidad entre la hemodiafiltración en línea (HDF) y la hemodiafiltración con reinfusión endógena (HFR). Material y método: Estudio comparativo observacional en una población de 15 pacientes en hemodiálisis crónica elegidos al azar entre los pacientes de nuestra unidad. Se compararon cambios en el perfil hematológico, nivel de PCR y constantes vitales, pre y post hemodiálisis, tras someterse a ambas técnicas de hemodiafiltración. Se comparó las diferencias entre los parámetros estudiados pre y post hemodiálisis en cada técnica. Resultados: Los niveles de plaquetas descendieron más en la HDF (HDF -1,33 vs HFR -19,73 x103/mm3, p=0,005). El nivel de leucocitos disminuyó en la HDF y aumentó en la HFR (HDF -0,46 vs HFR +0,8 x103/ mm3; p=0,006). Respecto a la fórmula leucocitaria hubo resultados dispares: segmentados HDF -1,7 vs HFR +5,4%, p<0,001; linfocitos HDF +1,96 vs HFR -3,62%, p<0,001. Con la HFR disminuyeron menos los niveles de PCR (HDF -0,05 vs HFR -0,001 mg/ dl; p=NS). En lo referente a las constantes vitales, la tensión arterial sistólica descendió más en la HFR que en la HDF (HDF -9,93 vs HFR -10,33 mmHg; p<0,001), a la inversa que la diastólica (HDF -5,2 vs HFR -3 mmHg; p=0,007) y la frecuencia cardiaca (HDF -1,46 vs HFR +1,73 lpm; p=NS). La temperatura corporal aumentó más con la HDF que con la HFR (HDF +0,35 vs HFR +0,06 ºC; p=NS). Conclusiones: Según nuestros resultados la HFR parece más biocompatible que la HDF, probablemente derivado por la reinfusión exógena de la HDF (AU)

Aim: To compare biocompatibility between online hemodiafiltration (HDF) and hemodiafiltration with endogenous reinfusion. Methods: Observational comparative study in a population of 15 chronic hemodialysis patients randomly selected among the patients in our unit. We compared changes in hematological profile, CRP level and vital signs, pre and post hemodialysis, after undergoing both hemodiafiltration techniques. Comparing the differences between the parameters studied before and after each hemodialysis technique. Results: Platelet levels decreased more in the HDF (HDF -1,33 vs HFR -19,73 x103/mm3, p=0,005). Leukocyte levels decreased in the HDF and increased with HFR (HDF -0,46 vs HFR +0,8 x103/mm3; p=0,006). Regarding the leukocyte formula had mixed results: segmented HDF -1,7 vs HFR +5,4%, p<0,001; lymphocytes HDF +1,96 vs HFR -3,62%, p<0,001. With the HFR decreased CRP levels less (HDF -0,05 vs HFR -0,001 mg/dl; p= NS). Regarding vital signs, systolic blood pressure decreased more in the HFR than HDF (HDF -9,93 vs HFR -10,33 mmHg; p<0,001), conversely that the diastolic blood pressure (HDF -5,2 vs HFR -3 mmHg; p=0,007), and heart rate (HDF -1,46 vs HFR +1,73 lpm; p=NS). Body temperature increased more with the HDF that the HFR (HDF +0,35 vs HFR +0,06 ºC; p=NS). Conclusions: According to our results the HFR seems more biocompatible than the HDF, probably derived by exogenous reinfusion of HDF (AU)

La diferencia entre tiempo programado y efectivo en hemodiafiltración en línea: ¿cada minuto cuenta en la eficacia dialítica? / The difference between programmed time and effective time in online haemodiafiltration: does every minute count in dialytic efficiency?

Introducción. El factor tiempo es determinante en la eficacia de la diálisis, recomendando las European Best Practices Guides of Dialysys Adequaccy una duración semanal no inferior a 720 minutos. Los modernos monitores de diálisis interrumpen el procedimiento por auto chequeos que incrementan la seguridad. Esos minutos de diferencia no han sido tenidos en cuenta en otros resultados obtenidos, algún autor ya hace referencia a la necesidad de contemplarlos. Los objetivos del presente estudio fueron determinar la diferencia real entre el tiempo programado y el tiempo efectivo de diálisis, y una vez comprobado incrementar la duración de la sesión para hacer que el tiempo efectivo sea realmente el deseado en cada paciente, y nunca inferior a 240 minutos por sesión. Finalmente comprobamos si existen diferencias en la eficacia dialítica, midiendo el Kt y el volumen total de reinfusión. Pacientes y métodos Diseñamos un estudio prospectivo sobre población prevalente en hemodiafiltración on-line. Reclutamos 152 pacientes en hemodiafiltración on-line. Durante 6 sesiones consecutivas (912 sesiones) la diálisis se efectuó con un tiempo programado ≥ 240 minutos. En un segundo periodo 6 sesiones consecutivas (912 sesiones), la sesión de diálisis se alargó hasta un tiempo efectivo igual al previo programado. La variable principal en estudio fue el tiempo, siendo variables secundarias el flujo sanguíneo, Kt, y volumen total de reinfusión. En el segundo periodo se recogieron posibles complicaciones intradialíticas en el tiempo añadido. Resultados Se analizan 152 pacientes, 66% hombres, de 65,7 ± 14,9 (26-88) años de edad, con una permanencia en diálisis de 56,5 ± 59,5 meses, en un total de 1824 sesiones de hemodiafiltración on-line. No se aprecian diferencias significativas en Qb (428,74±39,73 vs 429,86±38,54 ml/min). El tiempo medio de la sesión aumenta significativamente (p<0,001) en 7 minutos (de 233,58±3,29 hasta 240,67±2,71 minutos). El Kt aumenta significativamente (p<0,001) un 3,2% (desde 60,06±5,86 hasta 61,99±5,80 litros), disminuyendo el % de sesiones en las que no se alcanza el Kt deseado por superficie corporal (de 5,7% a 3,1%). El volumen total de reinfusión se incrementa significativamente (p<0,001) un 1,5% (de 24,10±2,72 a 24,46±2,77 litros), con un % similar de sesiones donde no se alcanzan los 20 litros objetivo (4,6% versus 4,3%). No se observan complicaciones intradialíticas en el periodo de tiempo incrementado ni episodios de coagulación...(AU)

Aim To determine the difference between programmed time and effective dialysis time, and once it has been found, to increase the duration of the session so that the effective time is actually as desired for each patient, and never less than 240 minutes per session. Finally, we determined whether there are differences in dialytic efficiency, by measuring Kt and total reinfusion volume. Patients and methods We designed a prospective study on the prevalent population in online haemodiafiltration. We recruited 152 patients undergoing online haemodiafiltration. For 6 consecutive sessions (912 sessions), the dialysis was carried out with a programmed time ≥ 240 minutes. In a second period of 6 consecutive sessions (912 sessions), the dialysis session was extended to an effective time equal to the previously programmed time. The principal variable in the study was time, with blood flow, Kt and total reinfusion volume as secondary variables. In the second period, any intradialytic complications in the added time were noted. Results A total of 152 patients were analysed, 66% of whom were man, 65.7 ± 14.9 (26-88) years old, with 56.5 ± 59.5 months on dialysis, in a total of 1824 online haemodiafiltration sessions. No significant differences in Qb were observed (428.74±39.73 v. 429.86±38.54 ml/min). The average duration of the session increased significantly (p<0.001) by 7 minutes (from 233.58±3.29 to 240.67±2.71 minutes). Kt increased significantly (p<0.001) by 3.2% (from 60.06±5.86 to 61.99±5.80 litres), with a reduction in the % of sessions in which the desired Kt per body surface area is not reached (from 5.7% to 3.1%). The total reinfusion volume increased significantly (p<0.001) by 1.5% (from 24.10±2.72 to 24.46±2.77 litres), with a similar % of sessions in which the target of 20 litres was not reached (4.6% compared to 4.3%). No intradialytic complications or coagulation episodes were observed in the increased time period. D...(AU)

Hemodiafiltración en línea pre-dilucional, frente a postdilucional: estudio comparativo de eficacia dialítica y tolerancia hemodinámica / Pre-dilution versus post-dilution on-line haemodiafiltration: a comparative study of dialytic efficacy and haemodynamic tolerance

La hemodiafiltración en línea es una técnica de diálisis que combina las ventajas de la hemodiálisis de alto flujo (transporte difusivo) y la hemofiltración (transporte convectivo). Esta técnica permite varias alternativas según se incorpore el líquido de reinfusión: pre-dilucional (antes del dializador) y post-dilucional (después del dializador), presentando cada una de ellas ventajas e inconvenientes. El objetivo de este estudio fue comparar distintos parámetros dialíticos y hemodinámicos entre los modos de hemodiafiltración pre y postdilucional. Se realizó un estudio prospectivo transversal en una población en diálisis que ya se trataba con hemodiafiltración en línea, sometiéndose durante 4 semanas a cada una de las modalidades (pre y post-dilucional). Se registraron los valores de: tensión arterial sistólica, diastólica y frecuencia cardiaca pre y post sesión, flujo de sangre, presión venosa, volumen de sangre dializado y volumen de sustitución. La dosis de diálisis se midió mediante dialisancia iónica. Se estudiaron 26 pacientes: 30% mujeres y 70% hombres, con una edad media de 61±13 años. El tiempo medio en tratamiento renal sustitutivo fue de 117±124,45 meses, tiempo medio en hemodiálisis fue de 50±54,38 meses. Los parámetros hemodinámicos no han presentado diferencias significativas entre las dos modalidades estudiadas (pre y post-dilucional). Se obtiene un mayor valor de KT estadísticamente significativo en la técnica de hemodiafiltración post-dilucional precisando ésta un volumen de sustitución de la mitad, en comparación con la modalidad predilucional. Conclusiones: La técnica de hemodiafiltración en línea es bien tolerada en las dos modalidades de infusión. Ante un mismo flujo de sangre, presión venosa y volumen de sangre dializado se consigue una mejor dosis de diálisis en el modo post-dilucional. La hemodiafiltración post-dilucional parece ser una mejor alternativa respecto a la pre-dilucional en relación a los parámetros estudiados siempre que no se tenga en cuenta la problemática de los accesos vasculares. Con dicha técnica logramos mejores resultados de KT precisando la mitad de volumen de sustitución, con el consiguiente ahorro de agua ultrapura. La hemodiafiltración pre-dilucional puede ser una alternativa para aquellos pacientes que no se consiga un flujo arterial alto(AU)

On-line haemodiafiltration is a dialysis technique which combines the advantages of high-flow haemodialysis (diffusive transport) and haemofiltration (convective transport). This technique allows different alternatives depending on how the reinfusion liquid is added: pre-dilution (before the dialyser) and post-dilution (after the dialyser), each of them having advantages and disadvantages. The object of this study was to compare different dialytic and haemodynamic parameters in the preand post-dilution haemodiafiltration modes. A transversal prospective study was conducted of a population in dialysis already being treated with on-line haemodiafiltration, using each of the modes (pre- and post-dilution) with them for 4 weeks. The following values were recorded: systolic and diastolic arterial pressure and cardiac frequency pre- and post-session, blood flow, venous pressure, volume of blood dialysed and replacement volume. Dialysis dosage was measured by means of ionic dialysance. 26 patients were studied: 30% women and 70% men, with an average age of 61±13 years. The average time under renal replacement treatment was 117±124.45 months, and the average time in haemodialysis was 50±54.38 months. The haemodynamic parameters showed no significant differences between the two modes studied (preand post-dilution). A statistically significant higher value for KT was obtained for the post-dilution haemodiafiltration technique, requiring half the replacement volume of the pre-dilution mode. Conclusions: The on-line haemodiafiltration technique is tolerated well in both infusion modes. With the same blood flow, venous pressure and volume of blood dialysed, a higher dialysis dosage was achieved using the post-dilution mode. Post-dilution haemodiafiltration appears to be a better alternative than the pre-dilution mode in terms of the parameters studied as long as the issue of vascular access is not taken into account. Better KT results were achieved with this technique, requiring half the replacement volume, with the resulting saving in ultra-pure water. Pre-dilution haemodiafiltration may be an alternative for patients where a high arterial flow cannot be achieved(AU)

The machine and the therapy concept.

Maintenance haemodialysis became established in mainstream clinical practice in the 1960s. For pragmatic reasons, diffusive dialysis was the technique which underpinned its success. Over the next 15 years it was shown that short- and medium-term survival depended only on a critical level of urea clearance being achieved. Uncomplicated technology with negligible capacity for middle molecule removal could deliver this and the case for developing more sophisticated machines able to broaden the spectrum of solute removal was unconvincing. Dialysis-related amyloidosis which was recognised in the mid-1980s as a devastating complication in long survivors disturbed this complacency. The journey to develop machines which could deliver broad-spectrum solute removal while exposing patients only to ultrapure fluids and biocompatible materials is described elsewhere in this text. The Lister Renal Unit was established in 1988. A fruitful collaboration between the multidisciplinary clinical team and engineering colleagues in the R&D Department of Fresenius contributed to a steady and in-depth understanding of the effect of superimposing convection on diffusive dialysis. From the outset only high-flux dialysis using ultrapure fluids was employed. Haemodiafiltration (HDF) was introduced in 1993. This paper summarises our observations regarding the relative contributions of natural renal function and convective blood purification to long-term outcomes. We have recently reported a 19-year experience which has allowed us to more clearly define the rationale for HDF in modern clinical practice. HDF is an engineering triumph which is likely to universally supersede diffusive dialysis. The challenge for clinicians moving forward is to learn in which treatment schedules this technology can best be deployed to improve the health prospects of patients with kidney failure.

The early years of on-line HDF: how did it all start? How did we get here?

In the mid-1980s, limits and side effects of contemporary hemodialysis were basically due to short treatment time, use of low-flux membranes and employment of acetate-buffered dialysate. These were already associated with a relatively high morbidity and cardiovascular mortality as part of diaysis-related pathology. Based on these considerations, the concept of on-line hemodiafiltration (HDF) was proposed as an innovative solution. By combining diffusive and convective clearances, HDF offered the most efficient modality to clear small and middle-sized uremic toxins. Furthermore, by using ultrapure dialysis fluid and high-flux synthetic membranes, HDF also offered the most biocompatible dialysis system, thereby going a long way towards preventing inflammation. Through provision of virtually unlimited amounts of sterile dialysis fluid by cold sterilization of fresh dialysate, on-line HDF offered an economical and viable method of conducting high-efficiency HDF (high volume exchange) therapy. By keeping the hemodialysis machine with all built-in technical options (e.g. adjustable blood pump, fluid-balancing system, conductivity meter, flow and pressure monitoring, bicarbonate-buffered dialysate), HDF benefited from being associated with the use of dialysis machines with excellent technology as well as highest safety standards. Use of ultrapure water made it then possible to produce dialysis fluid of intravenous grade quality with these machines. The first on-line HDF clinical trial was performed with a modified A2008C dialysis machine in 1984-85. This confirmed the feasibility and potential of the on-line HDF method. Some 25 years later, on-line HDF has proven to be safe, efficacious and with clinical benefits that justify it becoming a new standard for high-quality care of chronic kidney patients.

Avances en técnicas convectivas / No disponible

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Influencia en la dosis de diálisis de diferentes flujos de líquido dializante en el paciente tratado con hemodiafiltración on-line o hemodiálisis convencional / Influence on the dialysis doses of different flow rates of dialysis fluid in patients treated with online haemodiafiltration or conventional haemodialysis

La dosis de diálisis influye sobre la supervivencia del paciente en hemodiálisis, además de influir en la corrección de la anemia, en el estado nutricional y en el control de la tensión arterial, entre otros. Algunos autores han señalado el flujo del líquido dializante como un factor determinante de la dosis de diálisis del paciente en hemodiálisis de alto flujo y hemodiafiltración. El objetivo del presente estudio es evaluar el impacto en la eficacia de la diálisis de diferentes flujos de líquido dializante en pacientes tratados con hemodiafiltración on-line postdilucional y hemodiálisis convencional, mediante la medición del volumen convectivo final y del aclaramiento de pequeñas moléculas mediante el Kt. En todos los pacientes se realizan 9 sesiones de diálisis consecutivas variando el Qd: 3 sesiones con Qd 500 ml/min, 3 sesiones con Qd 800 ml/min y 3 sesiones con autoflujo . De los resultados obtenidos, el Kt se muestra significativamente mayor con Qd 800 ml/min (59,69 ± 6,07 litros) con respecto a Qd 500 ml/min (56,51 ± 6,33 litros, p<0,001) y autoflujo (58,02 ± 4,89 litros); así como el Kt del autoflujo mayor (p<0,001) que Qd 500 ml/min. El aumento del flujo de líquido dializante conlleva un incremento en la dosis de diálisis en pacientes tratados con hemodiafiltración on-line. El autoflujo consigue un incremento de dosis apreciable con respecto al Qd de 500 ml/min con un mínimo coste adicional, por lo que debería de considerarse como una medida en un esquema global de tratamiento, que permita la individualización en cada paciente (AU)

The dialysis dose affects survival of patients undergoing dialysis, as well as affecting the correction of anaemia, the nutritional state and the control of blood pressure, among others. Some authors have indicated the dialysis fluid flow rate as a determining factor in the dialysis dose for patients undergoing high-flow haemodialysis and haemodiafiltration. The aim of this study is to evaluate the impact on the dialysis efficacy of different flow rates of dialysis fluid in patients treated with on-line post-dilution haemodiafiltration and conventional haemodialysis, by measuring the final convective volume and rinse solution volume of small molecules using Kt. In all patients, 9 consecutive dialysis sessions were carried out varying the Qd: 3 sessions with Qd 500 ml/min, 3 sessions with Qd 800 ml/min and 2 sessions with autoflow. From the results obtained, Kt is shown to be significantly higher with Qd 800 ml/min (59.69 ± 6.07 litres) compared to Qd 500 ml/min (56.51 ± 6.33 litres, p<0.001) and autoflow (58.02 ± 4.89 litres); and Kt in autoflow was found to be higher (p<0.001) than Qd 500 ml/min. The increase in flow rate of dialysis fluid means an increase in the dialysis dose in patients treated with online haemodiafiltration. The autoflow achieves an appreciable increase in dose compared to Qd of 500 ml/min with a minimum additional cost, and should therefore be considered as a measure in an overall treatment framework, permitting individualization of treatment for each patient (AU)