Online hemodiafilteration use in children: a single center experience with a twist.

BACKGROUND: Haemodiafilteration (HDF) is a promising new modality of renal replacement therapy (RRT). It is an improvement in the quality of hemodialysis (HD) and thus in the quality of patients'lives. The main obstacle to using HDF is the cost, especially in developing countries. The purpose of this study was to evaluate the benefits of incorporating HDF with different regimens in the treatment of children with end stage renal disease (ESRD). METHODS: Thirty-four children with ESRD on regular HD in Pediatric Dialysis Unit, Children's Hospital, Ain Shams University were followed up in 2 phases: initial phase (all patients: HD thrice weekly for 3 months) and second phase, patients were randomized into 2 groups, HDF group and HD group, the former was subdivided into once and twice weekly HDF subgroups. Evaluation using history, clinical and laboratory parameters at 0, 3, 9 and 18 months was carried out. RESULTS: On short term, we found that the HDF group was significantly superior to HD group regarding all clinical and laboratory parameters. Also, twice HDF subgroup was significantly superior to once HDF subgroup. This was confirmed on long term follow up, but the once HDF proved comparable to twice subgroup. CONCLUSIONS: Incorporating online hemodiafilteration (OL-HDF) in the RRT of children was beneficial in most of the clinical and laboratory parameters measured. It's not all or non; OL-HDF, even once a week, can improve outcomes of HD without significantly affecting the cost.

Predilution On-Line Hemodiafiltration Improves Albumin Redox in Maintenance Hemodialysis Patients.

BACKGROUND/AIM: In this study, we compared the dialysis efficiency, oxidative stress, and nutritional conditions between predilution on-line hemodiafiltration (pre-OL-HDF) and conventional hemodialysis (HD) using a super-flux dialyzer (CHD). METHOD: This was a crossover study of 38 maintenance HD patients. All patients were treated with CHD for the first 4 months (1st CHD period), then were switched to pre-OL-HDF for 4 months (pre-OL-HDF period), and were returned to CHD for the next 4 months (2nd CHD period). RESULTS: We found no significant difference in the removal ratio of small uremic substances or the indices of inflammation or nutritional states between the pre-OL-HDF and CHD periods. However, we found higher removal of ß2 micro-globulin in the pre-OL-HDF period, and the human mercapto-albumin (Alb)/human serum Alb ratio was significantly higher in the pre-OL-HDF period. CONCLUSION: Treatment with pre-OL-HDF enabled enhanced removal of middle molecule uremic toxins and better Alb redox than did CHD.

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.

Online-haemodiafiltration vs. conventional haemodialysis: a cross-over study.

BACKGROUND: The main short-term advantages of haemodiafiltration (HDF) are supposedly better removal of Beta2-microglobulin (ß2-m) and phosphate, and better haemodynamic stability. The main disadvantage is higher costs. The aim of the study was to compare the clinical and biological parameters associated with HDF and high-flux haemodialysis (HD), using a cross-over design, while maintaining the same dialysis parameters. METHODS: All patients on a 3 × 4 hours schedule were observed during 3 identical 6-months periods: HDF1 - HD - HDF2. The mean values for the 2 last months of each period were compared. RESULTS: A total of 51 patients (76 % males, 45 % diabetic) with a mean age of 74 ± 15 years, and who had been on dialysis for 49 ± 60 months were included. The mean blood flow (329 ± 27 ml/min), dialysate flow (500 ml/min), and convection volumes (21.6 ± 3.2 L) were recorded. Patient medications were not changed. Predialysis blood pressure, phosphataemia, calcaemia, iPTH, Kt/V, nPNA and intradialytic events were similar throughout the 3 periods. Only serum albumin (34. 4 ± 3.6, 35.9 ± 3.4, 34.1 ± 4 g/L, p < 0. 0001) and ß2-m serum levels (26.1 ± 5.4, 28 ± 6, 26.5 ± 5 mg/L, p < 0.001, values shown for HDF1, HD, HDF2, respectively) were significantly lower during the HDF periods. Factor associated with higher delta serum albumin levels between HD and HDF periods was mainly a lower convection volume. CONCLUSION: Comparing HDF and HD, we did not observe any differences in haemodynamic stability or in serum phosphate levels. Only serum ß2-m (-6% vs. HD) and albumin (-5% vs. HD) levels changed. The long-term clinical consequences of these biochemical differences should be prospectively assessed.

The cost-utility of haemodiafiltration versus haemodialysis in the Convective Transport Study.

BACKGROUND: Despite the growing interest in haemodiafiltration (HDF), there is no information on the costs and cost-utility of this dialysis modality yet. It was therefore our objective to study the cost-utility of HDF versus haemodialysis (HD). METHODS: A cost-utility analysis was performed using a Markov model. It included data from the Convective Transport Study (CONTRAST), a randomized controlled trial that compared online HDF with low-flux HD. Costs were estimated using a societal perspective. Probabilistic sensitivity analyses were performed to study uncertainty. RESULTS: Total annual costs for HDF and HD were €88 622±19,272 and €86,086±15,945, respectively (in 2009 euros). When modelled over a 5-year period, the incremental cost per quality-adjusted life year (QALY) of HDF versus HD was €287,679. Sensitivity analyses revealed that this amount will not fall below €140,000, even under the most favourable assumptions like a high-convection volume (>20.3 L). CONCLUSIONS: Based on accepted societal willingness-to-pay thresholds, HDF cannot be considered a cost-effective treatment for patients with end-stage renal disease at present. Apparently, minor additional costs of HDF are not counterbalanced by a relevant QALY gain.

What can we expect from on-line hemodiafiltration?

On-line hemodiafiltration (ol-HDF) may improve clinical outcome in ESRD. The supposed mechanism is the improved clearance of uremic toxins by convective transport which is added to the diffusion transport. However, recent marked improvement in the performance of dialyzers has allowed higher removal rate of middle to large solutes by diffusion. It is inaccurate to define substances with a higher molecular weight such as uremic toxins. In addition, new methods should be developed for the removal of protein-bound substances. A technical fee for on-line HDF was newly established on the revision of the reimbursement for medical services Japan in 2012 and clearly separated from off-line HDF. As a facility requirement, the calculation of 'addition for maintaining dialysis fluid water quality' was added. Evidence for the clinical effects of ol-HDF have been reported mainly in Europe but is still inaccurate. To confirm the effectiveness of ol-HDF, randomized comparative trials on hemodialysis using super high-flux dialyzers and ol-HDF with same performance hemodiafilter are necessary.

What have we learned from CONTRAST?

The CONvective TRAnsport STudy (CONTRAST) is a large randomized controlled trial which compared on-line postdilution hemodiafiltration and low-flux hemodialysis in terms of mortality and cardiovascular events. This review summarizes and discusses currently available knowledge acquired by CONTRAST, including the main outcome, comparisons of hemodiafiltration to hemodialysis as well as studies performed in subgroups of CONTRAST.

The economic issue of on-line hemodiafiltration within the Japanese medical reimbursement system.

One major issue of Japan's health care system is that the Ministry of Health, Labor and Welfare (MHLW) centrally decides on the prices of medical services. Because of this, even if a treatment is deemed superior by the actual medical service provider, it may not be economically feasible to carry out. On-line hemodiafiltration has been reported to be an effective and favorable treatment modality, but the number of treated patients has declined since its approval in 2010 due to its low reimbursement price determined by MHLW. In this way, the problem with the Japanese medical reimbursement system is that MHLW's policy measures can thus affect the details of actual medical practices.

Cost-effectiveness analysis of on-line hemodiafiltration in Japan.

BACKGROUND/AIMS: Evaluation of the socioeconomic value of medical intervention and establishment of the resources necessary for clinical practice are important for new developments in medical technology. The aim of this study was to determine the socioeconomic value of on-line hemodiafiltration (HDF). METHODS: The subjects were 24 patients who underwent hemodialysis (HD) (9 HDF, 15 HD) for chronic renal failure. A total of 288 dialysis interventions were observed for 4 weeks in three clinics. Cost-effectiveness was evaluated based on quality-adjusted life years (Qaly) and a visual analog scale. RESULTS: EuroQOL-5D (0.776 ± 0.015) and visual analog scale (67.9 ± 1.2) in the HDF group were higher than those in the HD group at baseline. The incremental cost utility ratio for HDF was 641.7 (JPY 10,000/Qaly) based on Qaly (0.776 ± 0.015) and reimbursement for medical fees (JPY 4,982,736 ± 7,852), and was lower than the incremental cost utility ratio for HD. CONCLUSION: These results suggest that on-line HDF could be cost-effective.

Long-term efficacy of pre- and post-dilution online hemodiafiltration with dialyzer reuse.

OBJECTIVE: Growing evidence has demonstrated the potential survival benefit of online hemodiafiltration (HDF) over conventional hemodialysis (HD). Previous studies regarding online HDF utilized single-use dialyzer The present study was conducted to compare the long-term clinical parameters between pre- and post-dilution online HDF with the reuse dialyzer MATERIAL AND METHOD: This 2-year historical cohort study was conducted in 20 chronic hemodialysis patients who had undergone thrice-a-week pre-dilution online HDF for at least one year. The patients were switched to post-dilution online HDF for another year. Reuse dialyzers were utilized in both methods. RESULTS: No pyrogenic reactions had been detected throughout the 2-year study period. The C-reactive protein (CRP) and nutritional parameters were in good normal ranges. The normalization of protein equivalent of nitrogen appearance (nPNA) was significantly higher during the post-dilution period (1.25 +/- 0.22 vs. 1.11 +/- 0.14 g/kg/d, p < 0.01). Regarding adequacy of hemodialysis, the post-dilution online HDF showed significantly better Kt/V than the pre-dilution mode (2.46 +/- 0.35 vs. 2.35 +/- 0.35, p < 0.05) whereas the predialysis beta2-microglobulin levels were not different (23.43 +/- 5.35 vs. 23.73 +/- 5.55 mg/L, NS). The numbers of reuse were comparable (17.3 +/- 2.6 vs. 16.4 +/- 2.7, NS). CONCLUSION: Utilizing reuse dialyzer in online HDF could provide efficacy, safety, cost saving, and environmental benefit. The post-dilution technique yielded the better adequacy and nutritional status without causing the limitation in the reuse number and would be the standard mode-of-choice for online HDEF

A simple efficient technique of 'mid-dilution' on-line hemodiafiltration.

BACKGROUND: On-line hemodiafiltration (OL-HDF) with pre- as well as post-dilution reinfusion mode provides superior uremic toxin removal, especially middle uremic toxins, and can improve patient survival. Both standard pre- and post-dilution have limitations. Mid-dilution OL-HDF (Nephros OLpur) was invented to overcome the disadvantages of both standard modes, but such a cartridge is only available in limited centers and is expensive. METHODS: We created a simple technique of mid-dilution OL-HDF that can be easily set up in every hemodialysis center. Twelve stable end-stage renal disease patients were dialyzed in a random sequence with three different infusion modes of OL-HDF (simple mid-dilution, standard pre-dilution and post-dilution). Small molecule, middle molecule, and protein-bound uremic toxin clearances were measured. RESULTS: Simple mid-dilution OL-HDF provided high efficiency in uremic toxin clearances with less protein loss. CONCLUSION: Simple mid-dilution OL-HDF combines the advantages of pre- and post-dilution modes without adverse effects. Thus, this technique could be useful in decreasing morbidity and mortality in hemodialysis patients.

Matching efficacy of online hemodiafiltration in simple hemodialysis mode.

PUREMA H (referred to as PES) is an innovative dialysis membrane for enhanced low-molecular-weight (LMW) protein removal. The purpose of the study was to prove whether its efficacy in hemodialysis (HD) matches that of online hemodiafiltration (HDF) with conventional high-flux membranes. In a prospective, randomized, cross-over study on eight maintenance dialysis patients, treatment efficacy of HD with PES was compared with online postdilution HDF with the two synthetic high-flux membranes polysulfone (referred to as PSU) and Polyamix (referred to as POX). Apart from the infusion of replacement fluid, which was set at 20% of the blood flow rate of 300 mL/min, operating conditions in HD and HDF were kept identical. Small solute and LMW protein plasma clearances as well as the reduction ratio (RR) of cystatin C and retinol-binding protein were not different between the therapies. HDF with POX resulted in a significantly lower myoglobin RR as compared with HD with PES, and HDF with PSU. A 4% higher beta(2)-microglobulin RR was determined in HDF with PSU (73 +/- 5%) as compared with PES in HD (69 +/- 5%). The albumin loss was below 1 g for all treatments. Despite the fact that simple HD did not fully exploit the characteristics of PES, it achieved essentially similar LMW protein removal and albumin loss as compared with online postdilution HDF with the conventional synthetic high-flux membranes PSU and POX. Therefore, HD with PES may have beneficial effects on the outcome of maintenance dialysis patients similar to high-efficiency HDF.

[The concept of ultrapure solution online production]. / Il concetto di produzione online di liquido ultrapuro.

Online preparation of dialysis fluid, i.e., continuous mixing and immediate use, was introduced in 1964 and has contributed significantly to the expansion of dialysis therapy through simplified handling, improved microbiology, and enhanced efficiency. Online prepared replacement solution for hemofiltration was shown to be clinically safe as early as 1978, but the implementation was delayed for 20 years because of regulatory conservatism. Online preparation of sterile and pyrogen-free solutions for infusion is based on the use of water and concentrates that are mixed and distributed in a hygienically designed and maintained flow path. Ultrafilters with known retention capacity are placed in strategic positions to remove bacteria and endotoxins, which gives a sterility assurance level of at least six magnitudes, as required by the pharmacopoeia for sterile products. Microbiologic testing of the fluid should be applied when designing, validating, and troubleshooting online systems but not for routine quality control, because it only gives retrospective information. Quality assurance has to be built into a system and the way it is operated. The use of ultrapure dialysate must be considered as a suitable option for all hemodialysis modalities. To achieve this goal, one must keep in mind that ultrapure dialysate and infusate result from a complex chain of production where ultra-purity and/or sterility of the final solution relies on the weakest or worst component of the chain. Online fluid preparation, when properly performed, is safe, simple, and cost-effective and enhances the efficiency as well as the biocompatibility of dialysis therapy.

The use of alternative anti-coagulation strategies for a nocturnal home hemodialysis patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially catastrophic hyercoagulable state. The prevalence of HIT in individuals doing nocturnal home hemodialysis (NHD) is unknown and the appropriate treatment protocol has yet to be determined. The objective is to describe the clinical course and treatment plan ofa patient who developed HIT while undergoing NHD. A 49-year-old man with a past history of end stage renal disease (ESRD) of unknown etiology was initiated on NHD in February 2005. His clinical and biochemical parameters improved after conversion to NHD. However, excessive bleeding at the vascular access sites complicated his treatments. Clinical investigations revealed development of HIT Alternative therapeutic strategies were attempted to enable our patient to continue NHD: unfractionated heparin, citrated regional anticoagulation, Danaparoid, and Argatroban. In conclusion, NHD patients with HIT pose a specific clinical challenge. We speculate that the augmented exposure of heparin coupled with a primed autoimmune response may be responsible for the development of HIT in our patient. Further research is required to elucidate the appropriate clinical monitoring and treatment strategy for this patient.

Are There Any Downsides, Barriers, or Challenges in Delivering Hemodiafiltration in Everyday Clinical Practice?

There is considerable evidence to suggest that on-line hemodiafiltration (HDF) is superior to standard hemodialysis when comparing effects on clinical end points, especially when a certain minimum convection volume can be achieved. In this chapter we address the question of whether there are any downsides, challenges, or barriers in delivering on-line HDF in everyday clinical practice. We discuss the subject from a medical/practical point of view and briefly from a financial/economic perspective.

[Long-term intermittent renal replacement therapy at an intensive care unit].

Standard intermittent hemodialysis (IHD) used for the treatment of acute renal failure (ARF) at an intensive care unit has significant biochemical and physiological drawbacks. In the past 20 years, these drawbacks have stimulated the development of continuous renal replacement therapy (CRRT) and its ever-increasing use. However, CRRT is technically complicated and requires 24-hour monitoring. In some clinics, the use of CRRT leads to that each patient is under his/her nurse's surveillance, instead 1 nurse per 2 patients as before; this change has economic consequences and may limit nursing accessibility to other patients. The procedures prolonging intermittent therapy do not require 24-hour monitoring may benefit the treatment of ARF at the intensive care therapy. In this paper the authors call such procedures for continuous intermittent renal replacement therapy. They are characterized by a number of basic principles: (1) the use of modified or standard dialysis apparatuses; (2) the application of diffuse, convection, or both; (3) a certain reduction in the rate of elimination of dissolved substances as compared with IHD; (4) more prolonged treatment: above usual 3 or 4 hours of IHD, but not more than 8-12 hours (hence the term "intermittent"); (5) the use of on-line generation dialysate or substituting fluid. Information on the effectiveness and safety of this procedure is being now compiled.

Cost-Effectiveness Analysis of High-Efficiency Hemodiafiltration Versus Low-Flux Hemodialysis Based on the Canadian Arm of the CONTRAST Study.

AIM: The aim of this study was to assess the cost effectiveness of high-efficiency on-line hemodiafiltration (OL-HDF) compared with low-flux hemodialysis (LF-HD) for patients with end-stage renal disease (ESRD) based on the Canadian (Centre Hospitalier de l'Université de Montréal) arm of a parallel-group randomized controlled trial (RCT), the CONvective TRAnsport STudy. METHODS: An economic evaluation was conducted for the period of the RCT (74 months). In addition, a Markov state transition model was constructed to simulate costs and health benefits over lifetime. The primary outcome was costs per quality-adjusted life-year (QALY) gained. The analysis had the perspective of the Quebec public healthcare system. RESULTS: A total of 130 patients were randomly allocated to OL-HDF (n = 67) and LF-HD (n = 63). The cost-utility ratio of OL-HDF versus LF-HD was Can$53,270 per QALY gained over lifetime. This ratio was fairly robust in the sensitivity analysis. The cost-utility ratio was lower than that of LF-HD compared with no treatment (immediate death), which was Can$93,008 per QALY gained. CONCLUSIONS: High-efficiency OL-HDF can be considered a cost-effective treatment for ESRD in a Canadian setting. Further research is needed to assess cost effectiveness in other settings and healthcare systems.

What is the optimum dialysate flow in post-dilution online haemodiafiltration?

INTRODUCTION: In post-dilution online hemodiafiltration (OL-HDF), the only recommendation concerning the dialysate, or dialysis fluid, refers to its purity. No study has yet determined whether using a high dialysate flow (Qd) is useful for increasing Kt or ultrafiltration-infusion volume. OBJECTIVE: Study the influence of Qd on Kt and on infusion volume in OL-HDF. MATERIAL AND METHODS: This was a prospective crossover study. There were 37 patients to whom 6 sessions of OL-HDF were administered at 3 different Qds: 500, 600 and 700ml/min. A 5008(®) monitor was used for the dialysis in 21 patients, while an AK-200(®) was used in 17. The dialysers used were: 20 with FX 800(®) and 17 with Polyflux-210(®). The rest of the parameters were kept constant. Monitor data collected were effective blood flow, effective dialysis time, final Kt and infused volume. RESULTS: We found that using a Qd of 600 or 700ml/min increased Kt by 1.7% compared to using a Qd of 500ml/min. Differences in infusion volume were not significant. Increasing Qd from 500ml/min to 600 and 700ml/min increased dialysate consumption by 20% and 40%, respectively. CONCLUSIONS: With the monitors and dialysers currently used in OL-HDF, a Qd higher than 500ml/min is unhelpful for increasing the efficacy of Kt or infusion volume. Consequently, using a high Qd wastes water, a truly important resource both from the ecological and economic points of view.