Open access peer-reviewed chapter

# Cost-Effectiveness of Online Hemodiafiltration

By Khalid AlSaran and Khalid Mirza

Reviewed: June 23rd 2016Published: September 7th 2016

DOI: 10.5772/64679

## Abstract

Care of patients with end-stage renal disease (ESRD) is essential but also resource intense. We review several studies on online hemodiafiltration (OL-HDF), which concluded that high-volume OL-HDF is associated with better outcome compared to conventional hemodialysis. The cost-effectiveness of OL-HDF was shown in many studies. For example, in the Canadian setting of the Convective Transport Study (CONTRAST), the high-efficiency OL-HDF was shown to be cost-effective compared with low-flux hemodialysis (LF-HD) for patients with ESRD. In our study (Al Saran et al.), it was shown that the cost of hemodialysis was quite less in Saudi Arabia than in other industrialized countries while maintaining a high standard of care. In our retrospective analysis of the cost of OL-HDF in the same center, it was only 3% higher than the conventional HD, which indicates that it is cost-effective considering the improved hospitalization rate, the mortality rates, and the likely better quality of life associated with it. The trend of increased practice of OL-HDF may encourage the practice of home OL-HDF as well. It has been shown that home HD is more cost-effective than in-center HD and we presume that the same results will be applied to home OL-HDF as well.

### Keywords

• online hemodiafiltration
• low-flux hemodialysis
• middle molecules
• cost

## 1. Introduction

Untreated end-stage renal disease (ESRD) carries a high mortality. The management of ESRD is either by dialysis or by a kidney transplant. Due to insufficient number of kidney donors in comparison with the progressive increase in the number of ESRD patients in need for dialysis, dialysis remains the main modality of treatment. Since the care of patients with ESRD is resource intense, it is necessary to adopt measures that render the delivery of dialysis more cost-effective and improve the quality of care. The uremic syndrome is characterized by the accumulation of uremic toxins due to inadequate kidney function. The European Uremic Toxin Work Group has listed more than 90 compounds considered to be uremic toxins. Among them, 68 have a molecular weight less than 500 Da, 10 have between 500 and 12,000 Da, and 12 exceed 12,000 Da [1]. Solutes weighing less than 500 Da are considered low molecular weight solutes and they are removed by passive diffusion down a favorable concentration gradient. Urea is considered a marker of such toxins. Its clearance, as measured by Kt/V urea, correlates with patient morbidity showing the evidence that such toxins contribute to the uremic syndrome [2]. The mortality rate of patient on maintenance dialysis has been found to be 15–20% [3]. This is despite improvements in patient care and technology. In order to increase survival in dialysis patients, it was postulated in 1983 that increasing the Kt/V in conventional dialysis may help to reduce mortality. However, the hemodialysis (HEMO) study failed to show a positive effect on patient survival when dialysis dose per hemodialysis session was increased above the current K/DOQI recommendations [4]. Possible explanation for this unfavorable outcome could be in the kinetics of urea removal which is representative of small solutes, but not of larger-sized molecules such as middle molecules, large molecular weight proteins or protein-bound solutes, thereby making Kt/V misleading [5]. Clearance of urea accounts for only one-sixth of physiological clearance [1]. In addition, several shortcomings are associated with short dialysis schedules that are not captured by Kt/V index such as extracellular fluid volume control, phosphate control, and adequate removal of middle and larger uremic molecules compounds. Beta-2 microglobulin levels are associated with the development of dialysis-related amyloidosis and possibly reduced survival [6]. It seems likely that beta-2 microglobulin is a marker for overall-middle molecule clearance, including more toxic and yet unidentified uremic compounds [710]. Those solutes are better removed by high-flux membranes due to their more porous characteristics with increased permeability. Hemodialfiltration (HDF) is the treatment modality that combines diffusion and enhanced convection in order to facilitate removal of small molecular weight solutes. Moreover, small molecule removal is further increased with the use of high-volume OL-HDF. HDF is thus a more cardioprotective renal replacement therapy.

Recent randomized controlled trials (RCTs) have shown the survival advantage of HDF using high-convective volumes (23 L/session or 69 L/week prescription). In Peters et al.’s review [11] which is a pooled individual participant analysis of 4 RCTs, it was a observed that in patients receiving the higher delivered convection volume (>23 L per 1.73 m2 body surface area (BSA) per session), the longest survival benefit was seen withHazard Ratio (HR)of 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality and HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality.

In another study by Canaud et al. [12], which was a retrospective data collection from over 2000 patients with a minimum follow-up of 2 years, the relative survival rate of OL-HDF patients was found to increase at about 55 L–75 L/week of convection volume.

## 2. Principles of hemodiafiltration

Ultrafiltrate volume is removed by the dialysis machine through increased transmembrane pressure (TMP), whereas the replacement solution is infused intravenously at equal volume minus the desired fluid volume removal to preserve extracellular fluid balance and isovolemic state. The replaced solution represents substitution volume, whereas convective volume represents the sum of substitution volume and desired fluid volume removal during the dialysis session. The fluid can be substituted either after thedialyseras the reference mode (post-dilution mode) or before thedialyser(pre-dilution mode) or the combination of both (mixed dilution mode).

## 3. Efficacy of online hemodiafiltration

Several studies have shown online hemodiafiltration (OL-HDF) to be superior to conventional hemodialysis in reducing all-cause mortality in hemodialysis patients. OL-HDF has been found to reduce cardiovascular events as compared with conventional hemodialysis.

Furthermore, OL-HDF has significantly improved patients’ satisfaction and quality of life [1316]. OL-HDF has also shown to be a cost-effective treatment for ESRD [17]. For example, in the prospective Convective Transport Study (CONTRAST), there was no significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the OL-HDF and LF-HD groups, respectively); (hazard ratio, 0.95; 95% confidence interval, 0.75–1.20) after a mean follow-up of 3 years (range 0.4–6.6 years). Receiving high-volume hemodiafiltration during the trial was associated with lower all-cause mortality.

In the ESHOL multicentre, open-label RCT [14], patients on OL-HDF compared with those on HD had a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21–0.96; P = 0.03), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44–1.02; P = 0.06), and a 30% lower risk of all-cause mortality (HR, 0.70; 95% confidence interval [95% CI], 0.53–0.92; P = 0.01). In conclusion, high-efficiency post-dilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis. According to the Turkish OL-HF prospective RCT [15], 782 patients undergoing thrice-weekly HD were enrolled and randomly assigned in a 1:1 ratio to either postdilution OL-HDF or high-flux HD. Using a filtration volume of 17.2 ± 1.3 L, therewas no difference in the primary outcome between the two groups (event-free survival of 77.6% in OL-HDF vs. 74.8% in the high-flux group, P = 0.28). Also, no difference was seen in the cardiovascular and overall survival, number of hypotensive episodes and hospitalization rate. However on further analysis, the patients who received higher substitution volume (>17.4 L per session) had better cardiovascular outcome (P = 0.002) and overall survival (P = 0.03) compared with those who received high-flux HD. The study of Karkar et al. [16] aimed to investigate the effect of OL-HDF versus high-flux HD (HF) on a patient’s health-related satisfaction level. A higher satisfaction level was achieved by the OL-HDF group compared with HF group (p < 0.0001). In the OL-HDF group, there was less itching (9 ± 10 vs. 48 ± 10), less cramps (3 ± 5 vs. 55 ± 8), less joint pain and stiffness (24 ± 10 vs. 83 ± 8) with improvement in sexual performance (57 ± 10 vs. 5 ± 5), social activity (82 ± 9 vs. 15 ± 8), and general mood (94 ± 9 vs. 28 ± 16). High-efficiency postdilution online HDF versus high-flux HD significantly improved patients’ satisfaction and quality of life, including social, physical, and professional activities.

## 5. Conclusion

OL-HDF seems to be cost-effective and much better than conventional hemodialysis for the patient’s satisfaction, quality of life, patient’s survival, dialysis-related mortality and morbidity, and cardiovascular outcomes. However, more prospective studies are needed on the cost-effectiveness of this procedure.

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Khalid AlSaran and Khalid Mirza (September 7th 2016). Cost-Effectiveness of Online Hemodiafiltration, Advances in Hemodiafiltration, Ayman Karkar, IntechOpen, DOI: 10.5772/64679. Available from:

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