Dialysis
Table 1: Results of the Principal Studies Comparing Survival of End-stage Renal Disease Patients on Convective- versus Diffuse-base Therapies
Study (Author, Year) RRT Modalities Compared
Retrospective Cohort Studies Locatelli et al., 199968 Bosch et al., 200669 Canaud et al., 200670 Jirka et al., 200671 Vilar et al., 200972
Prospective Cohort Studies Vinhas et al., 200773 Panichi et al., 200874 Tiranathanagul, 200975
Survival on Convective Therapy
HDF or HF versus HD =
HDF versus LFHD versus HFHD ↑ 45 % HDF ± versus LFHD versus HFHD ↑ 35 % HDF versus LFHD versus HFHD ↑ 36 % ↑ 34 %
HDF versus HFHD
HDF versus HFHD HDF± versus LFHD HDF versus HFHD
Randomised Controlled Studies Locatelli et al., 199632
Wizemann et al., 200062 Schiffl et al., 200760 Santoro et al., 200876 Locatelli et al., 201045
HDF versus HFHD
versus LFHD versus CuHD HDF versus LFHD HDF versus HFHD HF versus HFHD
HDF versus HF versus LFHD
↑ 50 % ↑ 15 % =
=
= =
↑ 18 % =
CuHD = cuprophan haemodialysis; HD = haemodialysis; HDF = haemodiafiltration; HF = haemofiltration; HFHD = high-flux haemodialysis; LFHD = low-flux haemodialysis; RRT = renal replacement therapy.
Nutritional Status
Despite the fact that high-flux membranes and the use of ultrapure dialysis fluids are known to ameliorate protein-energy wasting,65
impact of HDF on the nutritional status of ESRD patients, compared with haemodialysis, appears to be small at best.18,32,60,62
the However, when
moving patients from a thrice-weekly HDF schedule (four to five hours per session) to a short daily HDF regimen (two to two and a half hours per session six times per week), it has been shown that the normalised protein catabolic rate increases significantly (+26.9 % at three months and +21.5 % at six months) and a trend in a higher body weight (+0.5 kg and +1.6 kg at three and six months, respectively) is also observed.15
Improvement of fluid overload,
diminution of post-treatment fatigue, increased removal of anorexic molecules (such as leptin) and better correction of acidosis and resistance to insulin, growth hormone and insulin-like growth factor-1 could have all contributed to these positive findings. Of note, similar findings have also been noted in frequent haemodialysis patients, as recently reviewed.66
Growth in Paediatric Patients
Switching paediatric ESRD patients from conventional, three-times-a-week dialysis to a daily HDF schedule was recently shown to improve quality of life, nutritional status and anaemia treatment.67
What is more, data
also showed an increase in growth velocities and a catch-up of curves (height standard deviation score from -1.2 to +0.2 during follow-up). The authors hypothesised that improved response to recombinant human growth hormone resulted from factors leading to improved nutrition and a diminution in cachexia.
1. U S Renal Data System, USRDS 2010 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, Bethseda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2010. 2. EBPG Expert Group on Haemodialysis, Section IV. Dialysis fluid
Hospitalisations
Studies evaluating the length or frequency of hospitalisations between HDF and conventional haemodialysis have, on aggregate, shown no statistically significant difference between treatment modalities. However, while trends towards a lower incidence of hospitalisations have been found (nearly 10 % in one study),68
no data, to our knowledge,
have yielded opposite tendencies. One can therefore conclude that HDF appears to be, at least, non-inferior to other RRT techniques in terms of patient hospitalisations. Further studies with better statistical power are, once again, needed to provide definitively conclusions on this topic.
Mortality
When addressing the impact of convective therapies on patient survival, little more than a dozen studies need to be taken into account (see Table 1). While most of these are observational – retrospective68–72 prospective73–75
or controlled fashion.32,45,60,62,76
– a few have nevertheless been realised in a randomised At first glance, one can already appreciate
that while most observational studies have shown a survival benefit with convective therapies, four out of five of the randomised controlled trials have, unfortunately, been negative. This situation is reminiscent of the results obtained when evaluating the impact of high- versus low-flux haemodialysis filters on ESRD patients outcomes: although large cohort studies have shown an association between high-flux membrane usage and a reduced mortality rate,77,78
the two largest randomised controlled
studies designed to answer the question, namely the Hemodialysis (HEMO)79
and the Membrane permeability outcome (MPO)80 been negative according to their primary analysis.
This difference between observational and randomised controlled trials can mainly be explained by confounding by indication in the first set of studies. In fact, although adjustments for patient characteristics tend to diminish such biases, there nevertheless most probably remained differences between subjects allocated to one RRT modality and not the other in those trials. By contrast, the randomised controlled trials could have been falsely negative because they were not sufficiently powered to demonstrate a survival difference between the different treatment groups (insufficient number of patients, follow-up period or mortality rate).
Conclusion
Online HDF constitutes a very attractive method of RRT. On the one hand, it has the capacity to eliminate a wider range of molecular-weight solutes through the added convective-base clearance it provides. On the other hand, its use of ultrapure water and better biocompatibility profile make it a less inflammatory technique. Clinical studies have demonstrated a positive impact of these technical aspects in lowering B2-microglobulin amyloidosis, improving phosphate control and diminishing the rate of symptomatic hypotensive episodes, among others. Unfortunately, no firm conclusion can be drawn, for the time being, relative to the hard end-point that constitutes mortality. Hopefully, ongoing randomised controlled trials comparing HDF with low- and/or high-flux haemodialysis (three of which have mortality as a primary end-point) should shed some light on this question in the near future.81–83
n purity, Nephrol Dial Tranplant, 2002;17:45–62.
3. Canaud B, Mion CH, Water treatment for contemporary hemodialysis. In: Jacobs C, Kjellstradn CM, Koch KM, Winchester JF (eds), Replacement of Renal Function by Dialysis (4th edition), Dordrecht: Kluwer Academic Publishers, 1996;232–55.
4. Pedrini LA, De Cristofaro V, Pagliari B, et al., Mixed predilution and postdilution online hemodiafiltration compared with the traditional infusion modes, Kidney Int, 2000;58:2155–65.
5. Pedrini LA, De Cristofaro V, On-line mixed hemodiafiltration with a feedback for ultrafiltration control: Effect on
studies, have
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