Dialysis
Haemodiafiltration – An Update
Muriel PC Grooteman,1 Piet M ter Wee, 1 Marinus A van den Dorpel4
Peter J Blankestijn,2 and Menso J Nubé1
Michiel L Bots, 3
1. Department of Nephrology, VU Medical Centre, Amsterdam; 2. Department of Nephrology, University Medical Centre Utrecht; 3. Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht; 4. Department of Internal Medicine, Maasstad Hospital, Rotterdam
Abstract
Today, an increasing number of patients with end-stage renal disease (ESRD) are treated by online haemodiafiltration (ol-HDF). In HDF, both diffusion and convection are combined. Growing evidence indicates that the high incidence of cardiovascular disease, as observed in patients with ESRD, is associated with the retention of uraemic toxins in the mid-molecular-weight range. As ol-HDF lowers these molecules more effectively than haemodialysis (HD), ol-HDF may improve outcome in patients with ESRD. In addition to a description of technical issues and solute removal, various conditions that may improve with HDF treatment are discussed, such as the micro-inflammatory and nutritional state, haemodynamic instability, quality of life, erythropoietin resistance and survival, as well as some potential drawbacks. With respect to survival, most studies are observational in nature and may suffer from biased therapy allocation. Currently, several randomised controlled trials with sufficient power to detect clinically relevant differences between HD and HDF are in progress, with the results expected in the upcoming years.
Keywords
Online haemodiafiltration, survival, convective clearance, uraemic toxins, ultrapure dialysate, micro-inflammation, haemodynamic stability, erythropoietin sensitivity
Disclosure: The authors are members of the Executive Committee of the CONvective TRAnsport STudy (CONTRAST). Financial support for this study is provided by a grant from the Dutch Kidney Foundation (Nierstichting Nederland grant C02.2019) and unrestricted grants from Fresenius Medical Care (The Netherlands) and Gambro Lundia AB (Sweden). Additional support was received from the Dr EE Twiss Fund, Roche Netherlands, the International Society of Nephrology/Baxter Extramural Grant Program and ZonMw (Dutch Organisation for Health Research and Development). Received: 22 January 2010 Accepted: 12 March 2010 Citation: European Nephrology, 2010;4:68–74 Correspondence: Muriel PC Grooteman, Department of Nephrology, VU Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. E:
mpc.grooteman@
vumc.nl
Today, an increasing number of patients with end-stage renal disease (ESRD) are treated with online haemodiafiltration (ol-HDF), especially in the European Community (see Figure 1).1
In HDF, diffusive and
convective transport are combined, providing optimal removal of both low- and mid-molecular-weight (MMW) substances, up to 40kDa. Growing evidence indicates that the high incidence of cardiovascular disease, as observed in patients with chronic kidney disease (CKD),2
is
associated with the retention of uraemic toxins in the mid- and high- mid-molecular-weight range (0.5–40kDa).3
As HDF lowers these
molecules more effectively than haemodialysis (HD), HDF treatment may reduce atherosclerotic complications and improve cardiovascular outcome in patients with ESRD. The development of sophisticated water purification systems in the last decade has allowed the online production of ultra-pure (UP) substitution fluid and high convection volumes at acceptable cost. However, thus far no definite data arising from randomised comparisons on the effects of HDF on cardiovascular parameters and/or clinical end-points are available. In this overview, we will discuss several technical, biochemical and practical features of ol-HDF, with special emphasis on clinical aspects.
Technical Issues and Monitoring of Fluids
During ol-HDF, convective solute removal is increased by filtering considerable amounts of plasma water through a dialyser (see Figure 2). At the same time, sterile substitution fluids are infused directly into
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the bloodstream to maintain fluid balance, either before (pre-dilution) or after the dialyser (post-dilution). These fluids are manufactured online from the municipal water supply.4,5
Online production of substitution
fluids consists of water pre-treatment and purification, transport through a well-designed distribution circuit to the dialysis machines and several ultrafiltration (UF) steps in the machine itself. Water pre-treatment involves downsizing microfilters, water softener(s) and a filter with activated carbon. Softeners mainly remove calcium and magnesium, whereas activated carbon filters remove chlorine and chloramines. The purification system is based on one or two reverse osmosis (RO) units and/or an electro-deioniser (EDI). The RO modules remove most ions and virtually all organic compounds, including bacteria, viruses and pyrogens. An EDI unit removes inorganic ions. The water distribution circuit is designed as a loop system, constructed from stainless steel or appropriate synthetic materials and disinfected regularly by ozone, heat or chemicals. Storage tanks or dead-ends are avoided. Continuous high-speed flow minimises the risk of biofilm formation. Once the purified water enters the dialysis machine, it is mixed with acid and bicarbonate concentrates, as depicted in Figure 3. All approved dialysis systems contain at least two ultrafilters, which are regularly replaced, situated after the point where the concentrates are added. With the first ultrafiltration step, UP dialysis fluid is produced. A final ultrafiltration step then provides the substitution fluid. All manufacturers guarantee the sterility of substitution fluid, providing
© T O UCH BRIEFINGS 2010
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