There have been a number of interesting dialysis-related papers published recently. As always, our clinical specialists have been monitoring the publications and here is our summary of the papers we have found to be especially relevant.
Benefits of short daily HD reviewed
Improved quality of life was commonly seen across several studies when
patients were on short daily haemodialysis (SDHD) therapy, with significant
effects on physical as well as mental components. Improved control of
hypertension was found, and reduction or even discontinuation of
anti-hypertensive medication was possible in several cases.
Several studies also observed a reduction in parameters of cardiac
hypertrophy. Improved nutrition and less need for erythropoietin to manage
anaemia was also reported. Vascular access problems were similar, and data
on hospitalisation rates were inconclusive.
The above information resulted from a systematic literature search on studies
comparing SDHD to conventional HD with a minimum of ten patients in each
group, resulting in a selection of 17 original articles for review. The majority of
studies were performed in the USA or Italy, and all but one publication was less
than ten years old. No randomised controlled trial was found.
Puñal J et al; Nephrol Dial Transplant 2008;23:2634-46
[http://ndt.oxfordjournals.org/cgi/content/abstract/23/8/2634]
RCT finds survival benefit with on-line HF therapy
A multi-centre study enrolled and randomised 64 patients to on-line predilution
haemofiltration (HF) or to low-flux HD with a synthetic membrane and
ultrapure dialysis fluid, and followed them for three years. Dropout was high
as 23 patients withdrew for various reasons and 19 died during the study.
74% of the deaths had a cardiovascular cause.
The number of deaths was lower in the HF group, and a Cox regression
analysis revealed an age-adjusted mortality odds ratio of 0.45 for on-line HF
(95% cI: 0.21-0.99).
Hospitalisation events were similar in number, but average length of stay was
four days shorter in the HF arm (p<0.001). Biochemical performance measures
were similar at study end, except for lower urea Kt/V (1.07 vs. 1.42) and lower
plasma 2 microglobulin level (24 vs. 37 mg/l) in the HF study arm.
Ref: Santoro A et al; Am J Kidney Dis 2008;52(3):507-18
Dialysis effects on vitamin levels investigated
Blood levels of water-soluble vitamins and homocysteine were investigated
pre- and post-dialysis in 30 prevalent HD patients, half of whom were on a
high-flux dialyser. All received multivitamin supplements routinely.
The change in blood level during dialysis correlated with the molecular
weight, and for all vitamins the change was independent of membrane flux
properties. Serum levels of folate and pyridoxal-5’-phosphate (PLP) were
reduced by approximately 35%, while red blood cell folate levels were stable.
Levels of thiamine and riboflavin were only reduced by 5-10%, and
cobalamin was apparently unaffected by dialysis. The only difference seen
between high- and low flux dialysis was in the homocystein reduction level,
being 48% in the high-flux dialysis versus 37% in the low-flux group.
The authors recommend monitoring of vitamin status in dialysis patients
regardless of which membrane type is used.
Ref: Heinz J et al; Nephrology 2008;13(5):384-9
[http://www3.interscience.wiley.com/journal/120124531/abstract]
The role of sodium level in dialysis fluid
The relations between the prescribed dialysis fluid sodium level and
interdialytic weight gain and incidence of intradialytic hypotension was
evaluated cross-sectionally in 2187 dialysis patients. A 140 mmol/l sodium
level was used for 63% of patients while another 25% were dialysed against
138 mmol/l sodium.
While target dry weight was independent of the fluid sodium level the
interdialytic weight gain was higher for patients on higher sodium, especially
for the first dialysis of the week. Pre- and post-dialysis blood pressure data
were similar between groups, except for a lower pre-dialysis pulse pressure in
the low sodium group.
Symptomatic hypotension during dialysis occurred more frequently in
patients on a higher sodium fluid. The authors consider their findings
supportive of using a lower sodium concentration in the dialysis fluid.
Ref: Davenport A et al; Int J Artif Organs 2008;31(5):411-7
[http://www.ajkd.org/article/S0272-6386(08)00888-3/abstract]
The choice of dialyser matters
The recently presented initial data from the European Membrane Permeability Outcome
(MPO) study strengthens the evidence that the middle molecule removal offered by high-flux
dialysis membranes is clinically important.
This study enrolled only new patients to dialysis and focused on those at risk,
characterised by having a serum albumin level below 4 g/dl. Patients randomised to start
dialysis with a high-flux rather than a low-flux membrane showed a significant 37% risk
reduction for all-cause death, after case mix adjustment. Diabetic dialysis patients also
showed a significant risk reduction with high-flux membranes. We eagerly wait for the full
MPO study data to be published.
Meanwhile the HEMO study, which reused dialysers to a large extent, failed to show a
significant effect of membrane flux on all-cause mortality in the full study population of
prevalent dialysis patients. However, patients already on dialysis for some years responded
differently, with improved survival when randomised to a high-flux membrane.
Recently published post hoc analysis of the HEMO study data indicates that in these
patients cardiac death is significantly associated with the amount of middle molecule
removal, expressed as b2-microglobulin (b2m) Kt/V. Each 0.1 unit increase in b2m Kt/V was
associated with a 7% risk reduction for cardiac death. A similar risk reduction, although not
significant, was seen for infectious death.
A recent paper from US investigators highlighted that synthetic high-flux membranes may
differ significantly in their capacity to remove middle molecules during HD treatments.
In direct cross-over comparisons of different high-flux dialyser brands, they found small
molecule removal to be mainly unaffected by membrane composition, while large molecule
removal depended significantly on membrane composition and morphology. Polyflux®
high-flux dialysers showed efficient removal of b2m as well as of other middle molecules
(angiogenin, leptin and complement factor D).
Presentation by Prof. F.Locatelli during the ERA-EDTA Congress 2007.
Cheung AK, et al: Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO study.
J Am Soc Nephrol. 2003;14(12):3251-63.
Cheung AK, et al: Association between serum 2-microglobulin level and infectious mortality in hemodialysis patients.
Clin J Am Soc Nephrol. 2008;3(1):69-77.
Long term follow-up of clotting incidence at reduced heparinisation with the AN69ST dialyser
In a single-centre study, 170 regular HD patients were randomised to be dialysed either with
a heparinised AN69ST dialyser at a reduced dose of unfractionated heparin (2718±1388 U)
or another dialyser at regular heparin dose (4800±1555 U). Over 15 months 26,626 sessions
were provided with registration of clotting events.
Moderate clotting in the drip chamber was more frequently seen in the
low-heparin group, as well as red patches in the dialyser at treatment end.
However, massive clotting was similar in the two groups, with 1.4 events/1,000
sessions in the AN69ST/low heparinised group versus 1.6 events/1,000 sessions
in the control group. Haemoglobin levels and erythropoietin needs remained
stable in both groups.
Chanard J et al; Nephrol Dial Transplant 2008;23:2003-9
(http://ndt.oxfordjournals.org/cgi/content/abstract/23/6/2003)
Better survival with short daily HD
The five-centre experience of 415 patients from Europe and the USA starting a
short daily HD programme between 1982 and 2005 has been reviewed.
Approximately two thirds of the patients were treated at home or in a self-care
unit, while the others were treated in-centre. Weekly StdKt/V was 2.9±0.6 and
2.6±0.5 for the US and European patients respectively.
The five-year survival in these patients was 68%. When compared to matched
patients in the USRDS registry, this was 2-3 times higher. The predicted time to
50% survival was 2-11 years longer in the short daily group.
Kjellstrand K et al; Nephrol Dial Transplant Advance Access May 5, 2008
Buttonhole cannulation practice reviewed
Expert opinions and historical insights into vascular access techniques for chronic
haemodialysis have been gathered in an email discussion club. Contributors with
experience in the buttonhole technique for patients with native arterio-venous
fistulas found benefits to be easier cannulation, reduced pain and reduced
aneurysm formation.
The paper discusses barriers to introducing the buttonhole technique and how
to overcome these. Advice is provided on needling protocols, track formation and
the preferred type of needle.
Murcutt G; Buttonhole cannulation: should this become the default technique for dialysis patients
with native fistulas? Summary of the EDTNA/ERCA Journal Club discussion Autumn 2007. J Ren Care. 2008 Jun;34(2):101-8
A high ultrafiltration rate is associated with increased mortality risk
A prospective observational study in 287 haemodialysis patients has found that patients who
died during the five-year observation period differed in several respects from those who
survived, including a greater intra-dialytic weight gain.
In a Cox proportional hazard survival analysis, adjusting for several covariates, the body
weight-adjusted UF rate appeared as an independent predictor of death (p<0.0001), while
intra-dialytic weight gain did not. The authors conclude that longer or more frequent sessions
should be considered in patients requiring high UF rates.
[Movilli E et al, Nephrol Dial Transplant. 2007;22(12):3547-52]
Clinical studies look at high-flux dialyzers
Two clinical studies performed by a team from Louisville, USA, benchmarked the
performance of high-flux dialyzers. Comparing the Gambro Polyflux H series to Fresenius
Optiflux and Polyflux S to the F series, the Polyflux filters respectively showed some 140%
and 75% greater clearance for beta-2-microglobulin.
Other middle molecules were also better cleared by the Polyflux dialyzers, while urea
and phosphate removals were similar. The paper emphasises that membranes made of
apparently similar polymers may differ substantially in the removal of small protein
uremic toxins.
[Ouseph R et al; Nephrol Dial Transplant Advance Access Dec 21, 2007]
Beta-2-microglobulin serum level is associated with infectious mortality in dialysis patients
A recent analysis of data from 1813 chronic HD patients participating in the HEMO study
found that for each 10 mg/l greater serum b2m level the risk for infectious death increased
by 21%, which was statistically highly significant. The effect was not dependant on how long
patients had been on dialysis.
This data supports the use of high-flux dialyzers to increase the removal of middle
molecules and the use of serum b2m level as marker of uremic toxicity.
[Cheung AK et al, Clin J Am Soc Nephrol 2008;3:69-77]
Cardiovascular death rate is less in patients treated with on-line HDF
A positive assessment of the effects of on-line HDF is an outcome of a
prospective observational study of all chronic HD patients in the northwest part
of the Tuscany region, Italy.
During a 30-month follow-up, all patients on on-line HDF treatment (17% of all)
were compared to those on HD (56%) or low-volume HDF with bagged reinfusion
fluid (27%). Both HDF groups showed better survival rates than the regular
HD group.
Inflammatory markers (CRP, IL-6) also correlated significantly with mortality
rates. Patients on on-line HDF showed significantly lower IL-6 levels than the
other groups.
[Panichi V et al, Nephrol Dial Transplant. 2008; Advance Access Feb 27, 2008]
American researchers investigate allergic reactions in haemodialysis patients
An outbreak of acute allergic-type reactions in US haemodialysis patients is being
investigated by the US Centers for Disease Control and Prevention (CDC). In a
report on their ongoing investigation, CDC states, 65 confirmed or probable
cases from mid November 2007 to mid January 2008. The following signs and
symptoms are reported:
A high ultra filtration rate is associated with increased mortality risk
A prospective observational study in 287 haemodialysis patients has found that patients who died during the five-year observation period differed in several respects from those who survived, including a greater intra-dialytic weight gain.
In a Cox proportional hazard survival analysis, adjusting for several covariates, the body weight-adjusted UF rate appeared as an independent predictor of death (p<0.0001), while intra-dialytic weight gain did not. The authors conclude that longer or more frequent sessions should be considered in patients requiring high UF rates.
[Movilli E et al, Nephrol Dial Transplant. 2007;22(12):3547-52]
Clinical studies look at high-flux dialyzers
Two clinical studies performed by a team from Louisville, USA, benchmarked the performance of high-flux dialyzers. Comparing the Gambro Polyflux H series to Fresenius Optiflux and Polyflux S to the F series, the Polyflux filters respectively showed some 140% and 75% greater clearance for beta-2-microglobulin.
Other middle molecules were also better cleared by the Polyflux dialyzers, while urea and phosphate removals were similar. The paper emphasises that membranes made of apparently similar polymers may differ substantially in the removal of small protein uremic toxins.
[Ouseph R et al; Nephrol Dial Transplant Advance Access Dec 21, 2007]
Beta-2-microglobulin serum level is associated with infectious mortality in dialysis patients
A recent analysis of data from 1813 chronic HD patients participating in the HEMO study found that for each 10 mg/l greater serum b2m level the risk for infectious death increased by 21%, which was statistically highly significant. The effect was not dependant on how long patients had been on dialysis.
This data supports the use of high-flux dialyzers to increase the removal of middle molecules and the use of serum b2m level as marker of uremic toxicity.
[Cheung AK et al, Clin J Am Soc Nephrol 2008;3:69-77]
Cardiovascular death rate is less in patients treated with on-line HDF
A positive assessment of the effects of on-line HDF is an outcome of a prospective observational study of all chronic HD patients in the northwest part of the Tuscany region, Italy. During a 30-month follow-up, all patients on on-line HDF treatment (17% of all) were compared to those on HD (56%) or low-volume HDF with bagged reinfusion fluid (27%). Both HDF groups showed better survival rates than the regular
HD group. Inflammatory markers (CRP, IL-6) also correlated significantly with mortality rates. Patients on on-line HDF showed significantly lower IL-6 levels than the other groups.
[Panichi V et al, Nephrol Dial Transplant. 2008; Advance Access Feb 27, 2008]
American researchers investigate allergic reactions in haemodialysis patients
An outbreak of acute allergic-type reactions in US haemodialysis patients is being investigated by the US Centers for Disease Control and Prevention (CDC). In a report on their ongoing investigation, CDC states, 65 confirmed or probable cases from mid November 2007 to mid January 2008. The following signs and symptoms are reported: