Download What are the short-term and long-term consequences of anaemia in

Nephrol Dial Transplant (1999) 14 [Suppl 2]: 29–36
Nephrology
Dialysis
Transplantation
Chairman’s Workshop Report
What are the short-term and long-term consequences of anaemia in CRF
patients?
J. F. E. Mann
Department of Nephrology, Schwabing Hospital, Ludwig-Maximilians University, Munich, Germany
Workshop Participants: P. Bárány, Sweden; N. Clyne, Sweden; A. J. Collins, USA; R. N. Foley, Canada; T. P. Hannedouche,
France; F. Locatelli, Italy; G. M. London, France; H. P. H. Neumann, Germany
Abstract There is a clear relationship between anaemia
and cardiovascular risk in chronic renal failure (CRF )
patients. Left ventricular hypertrophy (LVH ) is present
in about three-quarters of patients starting dialysis,
and is a strong predictor of mortality. Anaemia contributes to the development of LVH, mainly via
increased cardiac output. In some patients, anaemia
results in an increase in LV mass, while in others it
also results in LV end-diastolic volume dilatation.
These changes increase the risk of arrhythmias,
myocardial infarction and myocardial fibrosis. The
lower the haemoglobin, the more likely it is that LVH
and heart failure will develop. Furthermore, a haemoglobin of <11 g/dl is associated with increased morbidity and mortality. Partial correction of anaemia with
epoetin leads to a partial, but not complete, reversal
of LVH. One large prospective study (Lombardy
Registry) found that epoetin treatment was accompanied by a 30% reduction in crude relative risk of
mortality. A progressive reduction in the relative risk
of general and cardiovascular mortality was found
with increasing haematocrit, with and without adjustment for co-morbid conditions. Mean hospitalizations
also decreased with increasing haematocrit. The longterm effects of normalized haematocrit/haemoglobin
values in uraemic patients have not yet been evaluated
exhaustively in prospective, randomized, multicentre
studies. Epoetin treatment has been shown to induce
lasting improvements in patients’ sense of well-being,
reduce fatigue, increase appetite and work capacity,
and improve exercise tolerance, libido and work performance. Further studies are needed to demonstrate
whether greater haemoglobin concentrations are associated with greater improvements in quality of life
during epoetin treatment.
Key words: epoetin; haemoglobin; left ventricular
hypertrophy; morbidity; mortality; quality of life
Correspondence and offprint requests to: Professor Dr Johannes F. E.
Mann, VI Medizinische Abteilung, Klinikum Schwabing, Kölner
Platz 1, 80804 München, Germany.
Introduction
This workshop had two primary objectives: (i) to
evaluate the impact of anaemia in chronic renal failure
(CRF ), particularly long-term effects on the heart and
short-term effects on quality of life; and (ii) to assess
how these parameters are affected when anaemia is
corrected with epoetin.
This article reviews the key issues considered by the
workshop participants:
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the importance of left ventricular hypertrophy
(LVH ) as a cause of morbidity and mortality in
CRF patients;
the mechanisms by which anaemia contributes to
the development of LVH;
the effects of epoetin treatment on LVH;
the relationship between haematocrit/haemoglobin
levels and mortality;
the effects of epoetin treatment on mortality and
hospitalization; and
the effects of epoetin treatment on quality of life.
The workshop participants agreed that there is a
clear relationship between anaemia and cardiovascular
risk in CRF patients. They then addressed the more
complex issue of whether correcting anaemia with
epoetin limits the development of LVH in CRF patients
and, if so, whether this leads to a reduction in morbidity or mortality.
LVH in end-stage renal disease
Cardiovascular disease is the main cause of death in
dialysis patients [1]. Almost half of all deaths in
patients with end-stage renal disease ( ESRD) are due
to cardiovascular events, particularly cardiac failure,
myocardial infarction (MI ) and sudden cardiac death
[2]. In a prospective cohort study of ESRD patients,
Foley et al. found that hospital admission for cardiac
failure preceded two-thirds of all deaths [3].
LVH is a frequently observed abnormality in both
ESRD patients and the general population. It is very
© 1999 European Renal Association–European Dialysis and Transplant Association
30
J. F. E. Mann
strongly associated with the de novo development of
ischaemic heart disease and cardiac failure. LVH predicts mortality independently of age, diabetes, hypertension, hyperlipidaemia and smoking, even when it is
asymptomatic [4]. In CRF patients, LVH develops
rapidly as the glomerular filtration rate (GFR) declines.
As a result, LVH is already present in ~75% of
patients starting renal replacement therapy [4].
In CRF patients, evidence of LVH at the start of
dialysis is strongly predictive of late mortality (>2
years on dialysis) [4]. This time lag is important as it
represents an opportunity for intervention to slow the
progression to irreversible cardiac disease. As there is
evidence to show that anaemia contributes to the
development of LVH in ESRD patients [5], correcting
anaemia in these patients may have a positive influence
on cardiovascular morbidity and mortality.
How does anaemia cause LVH?
When patients develop anaemia, several structural and
functional cardiovascular alterations occur. These
alterations are essentially adaptive because their ‘goal’
is to maintain oxygen delivery to the tissues and organs.
The most typical haemodynamic change observed is
an increase in cardiac output due to both an increased
stroke volume and an increase in heart rate. Several
mechanisms are responsible, including:
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a reduction in afterload due to a decrease in
systemic vascular resistance;
an increase in pre-load due to an increase in venous
return; and
an increase in LV function, attributed to an
increase in sympathetic activity and to noncatecholamine inotropic factors [6–8].
Vascular resistance decreases as a result of arterial
dilatation and reduced blood viscosity. The arterial
dilatation is due to an increase in arteriolar diameter,
the recruitment of new vessels and the formation of
collaterals and arteriovenous shunts. Several mechanisms have been proposed as being responsible for
these vascular changes: ‘hypoxic vasodilatation’, ‘flowmediated vasodilatation’ due to increased blood flow
resulting from tachycardia, and increased inotropic
state. The reduction in blood viscosity is a direct result
of the reduced number of erythrocytes in anaemic
patients.
Venous return increases as a result of reduced resistance to venous return. In anaemic patients, resistance
to venous return decreases in parallel with the decrease
in haemoglobin and viscosity. In addition, arterial
dilatation facilitates pressure transmission from the
arterial system to the venous circulation. This creates
a favourable pressure gradient for venous return.
Finally, the increased sympathetic activity that occurs
in anaemic patients could, theoretically, induce active
venoconstriction, favouring cardiac filling.
Increased ventricular performance can result from
an increase in pre-load (Frank–Starling mechanism),
as well as from changes in inotropic state, due to
increased sympathetic activity. Increased cardiac preload and the high output state produce a long-term
increase in heart rate, which leads to progressive
enlargement of the heart cavities and the development
of eccentric LVH.
London et al. have clearly demonstrated that there
is an association between the anaemia of ESRD and
the development of LVH [1]. Compared with age- and
blood pressure-matched controls, anaemic patients
with ESRD show a marked increase in cardiac index.
These acute, short-term changes subsequently translate
into adaptations of the cardiac ventricle and large
vessels. Haemoglobin concentrations correlate with
both LV end-diastolic volume and LV mass ( Figure 1)
[1]. There appear to be two types of patient: one in
whom anaemia results in an increase in LV mass only,
and another in whom it also results in LV end-diastolic
volume dilatation.
The anaemia of ESRD also has marked effects on
the large arteries [7]. London et al. have shown that
the diameter of the common carotid artery is significantly increased in patients with ESRD. The crosssectional area and medial muscle thickness are also
increased, while muscle distensibility is reduced. When
these changes are combined with the increased flow
velocity that is seen characteristically in anaemic CRF
patients, there is a risk that vessels will be predisposed
to premature atherosclerosis.
Although LV hypertrophy and LV dilatation might
appear to be ‘adaptive’ responses to hypoxia, the end
result is undoubtedly deleterious. CRF patients already
have a reduced coronary reserve due to anaemia. If
LVH is added to this clinical profile, there is an
additional decrease in maximum vasodilatory capacity
and coronary reserve. Low coronary reserve appears
to be an important factor predisposing patients to
arrhythmias, MI and myocardial fibrosis. It is not
surprising, therefore, that the combination of anaemia
and LVH is associated with an increased cardiac risk.
LVH and mortality
Studies of essential hypertension have shown that LVH
is associated with increased cardiovascular risk. The
same is true for CRF patients on dialysis.
Foley et al. followed a cohort of 432 ESRD patients
who survived at least 6 months, obtaining echocardiographic data annually during follow-up [3,4,9–16 ].
Many different parameters were studied, including the
impact of LVH on cardiovascular risk [15]. At the
onset of dialysis, 16% of patients had systolic dysfunction, 41% had concentric LVH and 28% had LV
dilatation. Only 16% had normal echocardiograms.
The median time to the development of heart failure
was 19 months in patients with systolic dysfunction,
38 months in patients with concentric LVH and 38
months in patients with LV dilatation. After adjusting
for age, diabetes and ischaemic heart disease, the
relative risks of heart failure in all three groups were
The short- and long-term consequences of anaemia in CRF patients
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Fig. 1. Correlation between haemoglobin (5 mmol/1=~8 g/dl ) and LV end-diastolic volume and mass in dialysis patients. (Reproduced
with permission from [1]).
significantly worse than in the group with normal
echocardiograms.
The data on survival are shown in Figure 2 [13]. In
this cohort, median survival was 38 months in patients
with systolic dysfunction, 48 months in patients with
concentric hypertrophy and 56 months in patients with
LV dilatation, compared with >66 months in patients
with normal echocardiograms.
The same researchers also examined the relationship
between haemoglobin at the beginning of dialysis and
subsequent echocardiographic changes [3]. These data
illustrate that as anaemia worsens, dialysis patients are
at greater risk of LV dilatation and heart failure, and
early death. After adjusting for age, diabetes, ischaemic
heart disease, blood pressure and serum albumin, each
1 g/dl decrease in mean haemoglobin was associated
independently with the presence of LV dilatation on
repeat echocardiograms as well as with the development of de novo and recurrent cardiac failure (Figure 3)
[3]. In addition, each 1 g/dl decrease in mean haemoglobin was associated independently with mortality.
There was no independent association between anaemia and the development of ischaemic heart disease in
these patients.
A small subgroup analysis of patients using multiple
echocardiograms indicated that most of the increase
Fig. 3. Effect of a 1 g/dl decrease in haemoglobin on the odds ratio
for various echocardiographic and clinical outcomes in haemodialysis
patients. (Data from [3]).
in LVH occurred during the first year on dialysis. This
implies that it is better to try to reduce LVH and
cardiovascular risk by treating anaemia early.
Logically, the greatest benefit would be expected if
treatment were started during the pre-dialysis phase.
However, as discussed below, it must first be proven
that a reduction in LVH in CRF patients does indeed
reduce mortality.
Could epoetin treatment delay mortality?
Given that anaemia results in LVH and that LVH is a
risk factor for mortality, correcting anaemia with epoetin should reduce premature deaths among CRF
patients. Evidence from large, carefully controlled,
clinical studies is still needed to confirm this supposition. In the meantime, there is encouraging indirect
evidence for a beneficial effect of epoetin treatment on
mortality:
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Fig. 2. Survival in patients with systolic dysfunction, concentric
LVH and LV dilatation, compared with patients with normal
echocardiograms. (Reproduced with permission from [13]).
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in essential hypertension, treatments that reduce
LVH do reduce mortality [17];
partial correction of anaemia with epoetin partially
reverses LVH (see below); and
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J. F. E. Mann
CRF patients with increased haemoglobin have a
reduced risk of death and hospitalization compared with CRF patients with lower haemoglobin.
It is possible that further beneficial cardiovascular
effects would be seen with full correction of anaemia.
However, some of these benefits may be offset by
adverse effects on other cardiovascular parameters,
such as blood pressure and blood viscosity. The extent
to which anaemia is corrected as well as the nature
and severity of underlying diseases may also affect the
risk–benefit balance. As discussed elsewhere in this
Supplement, several large clinical trials in which
haemoglobin was increased to normal have recently
been completed. It is hoped the results will elucidate
further whether full correction of anaemia has positive
effects on cardiovascular mortality and morbidity.
Epoetin and regression of LVH
Several studies show that correcting anaemia with
epoetin both improves the function and modifies the
structure of the cardiovascular system in patients with
ESRD [18–22]. Of particular note is the finding that
partial correction of anaemia with epoetin partially
reverses LVH.
Wizemann et al. [21] studied 28 anaemic normotensive haemodialysis patients with LVH who were treated
with epoetin for 16 months. The aim was to increase
the haematocrit to 35%. The partial correction of
anaemia achieved in this study resulted in a decrease
in the mean LV end-diastolic diameter from 52.6 to
49.6 mm at 4 months (P<0.01) and to 47.9 mm at 16
months (P<0.001). There was a slight decrease in LV
end-systolic diameter (30.4 vs 32.6 mm, P <0.05) and
LV posterior wall thickness (12.1 vs 12.8 mm, P <0.05)
at 16 months. The calculated mean LV muscle mass
index was reduced from 199 to 173 g/m2 at 4 months
(P<0.01) and to 160 g/m2 at 16 months (P<0.001).
Mean resting heart rate was reduced significantly from
80 to 73 (P<0.01) at 4 and 16 months. LV ejection
fraction, thickness of LV septum and blood pressure
did not change.
Haemodynamic studies [19, 20, 22, 23] have revealed
that cardiac output decreases and total peripheral
resistance increases during epoetin therapy. The distribution of cardiac output during epoetin treatment has
not been addressed specifically, but a decrease in
forearm and calf blood flow with an increase in local
resistance has been observed.
Decrease in cardiac output
The decrease in cardiac output seen during epoetin
therapy is due to a reduction in stroke volume and a
decrease in heart rate. The reduction in stroke volume
can result from either a decrease in venous return or
an increase in peripheral resistance. The decrease in
venous return is partially prevented by an increase in
peripheral venous tone, which helps to maintain
adequate venous return and cardiac filling. It is
unknown whether the change in venous tone results
from active venoconstriction or from passive recoil.
The decrease in heart rate is due to decreased myocardial contractility and decreased neurosympathetic
outflow.
Increase in peripheral resistance
The increase in peripheral resistance seen during epoetin therapy is a direct consequence of increased
haemoglobin and blood viscosity. Nevertheless, the
increase in peripheral resistance seen in some patients
is not in proportion to the changes in blood viscosity,
and arterial hypertension may develop. Under these
conditions, the increased peripheral resistance could
be due to: (i) a direct vasomotor effect of epoetin on
vascular smooth muscle cells; or (ii) an altered interaction between blood rheological properties and vascular walls through abnormal endothelial function.
The functional changes that occur during epoetin
therapy are paralleled by structural alterations, i.e. a
decrease in the internal dimensions of the left ventricle
and a partial regression of LVH. To date, no structural
changes due to epoetin have been reported in the
arterial or venous systems.
Haemoglobin and mortality
The relationship between mortality and haemoglobin
in haemodialysis patients has been investigated in
several observational studies. Most indicate that low
haemoglobin concentrations are associated with increased mortality. The National Kidney Foundation–
Dialysis Outcomes Quality Initiative (NKF–DOQITM )
reviewed the literature on both pre-dialysis patients
and dialysis patients within and outside the US.
This analysis showed that, compared with higher
values, a haemoglobin of <11 g/dl is associated with
increased morbidity and mortality [24]. However, the
long-term effects of normalized haemoglobin in
uraemic patients have not yet been evaluated exhaustively in prospective, randomized, multicentre studies.
US studies
Madore et al. [25] studied 18 792 US National Medical
Care (a large provider of dialysis services) patients,
assessing their haemoglobin values during the last 3
months of 1992, with follow-up into 1993. They found
that, after adjustment for case mix, patients with
haemoglobin of ∏8 g/dl had a 2-fold increase in the
odds of death compared with those with a haemoglobin
of 10–11 g/dl. There was no further reduction in the
odds of death for patients with a haemoglobin of
>11 g/dl. However, it is likely that many patients
receiving high doses of epoetin in this study were
severely ill because the reimbursement system in the
US influenced how much epoetin was prescribed. No
reliable conclusions can therefore be drawn from this
study regarding the effect of higher haemoglobin on
the risk of death.
The short- and long-term consequences of anaemia in CRF patients
In a much larger observational study, Collins et al.
analysed data from 74 598 haemodialysis patients in
the US Medicare system, using a Cox regression model.
There was a 6 month entry period during 1993 and a
1 year follow-up period. The analysis showed that
mortality risk was 1.51 in patients with a haematocrit
of <27%, 1.20 in patients with a haematocrit of
27–30% and 0.90 in patients with a haematocrit of
33–36% [26 ]. All values were highly significant vs the
reference haematocrit of 30–33% ( Figure 4) [26 ]. A
multiple hospitalization risk model showed similar
results [27]: haematocrits of 33–36% were associated
with a 0.89 risk of multiple hospitalizations, haematocrits of 27–30% were associated with a 1.13 risk and
haematocrits of <27% were associated with a 1.30
risk. This study concluded that higher haematocrits
were beneficial, with the greatest benefit seen at the
highest haematocrits.
Length of stay in a hospital was also plotted against
haematocrit and the number of co-morbid conditions.
These data revealed that, as haematocrit decreased,
there was a dramatic increase in the number of days
spent in hospital in the subsequent year. This trend
was more marked as the number of co-morbid conditions increased. Patients with a haematocrit of <27%
and 10 co-morbid conditions spent 25 days in hospital,
whereas those with a very high haematocrit and no
co-morbid conditions spent almost no days in hospital.
For each level of co-morbid condition, the higher the
haematocrit, the lower the number of days spent in
hospital.
The Lombardy Registry
Between 1 January 1983 and 31 December 1995, the
Lombardy Dialysis and Transplant Registry analysed
5302 CRF patients (mean age: 54.9±16.1 years) on
dialysis treatment who were alive on 31 December
1995 and fulfilled the inclusion criteria [28]. Survival
in the calendar year 1996 was evaluated by means of
the Kaplan–Meier and Cox proportional hazards
methods, considering the covariates of age, gender,
co-morbidity, treatment modality and three classes of
haematocrit value (<27%, 27–32% and >32%). This
study differed from the US studies in that it also
Fig. 4. Risk of death according to haematocrit in 74 598 haemodialysis patients in the US Medicare system during 1993, using a
Cox regression model. 95% confidence intervals are included. (Data
from [26 ]).
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attempted to establish the relationship between epoetin
treatment and outcome.
Age at entry, cachexia and neoplasia were all significant risk factors for mortality, whereas the use of
epoetin was accompanied by a 30% reduction in the
crude relative risk of mortality. However, Locatelli
et al. [28] have underlined that even though the prediction rate of the model for all-cause mortality was
generally good (88%), it failed to predict the events
correctly (5%) because of the low number of events.
A progressive reduction in the relative risk of general
(statistically significant) and cardiovascular mortality
was found up to the highest haematocrits, with or
without adjustment for co-morbid conditions
( Figure 5). Mean hospitalizations also decreased with
increasing haematocrit (Figure 6) [28].
It was surprising to note that about half the patients
in this study had a haematocrit of <30%, which is
substantially below the 33–36% currently recommended by the NKF-DOQITM guidelines [24].
Japanese study
In contrast to the findings described above, a recent
Japanese retrospective study of 2116 CRF patients
reported that the introduction of epoetin therapy was
associated with an increased risk of cardiovascular
disease [29]. However, the authors themselves acknowledged that, due to the retrospective nature of their
study, any causal relationship between epoetin use and
the risk of cardiovascular disease should be interpreted
with caution.
In this study, the trend towards an increase in the
Fig. 5. Overall mortality in 5302 patients from the Lombardy
Registry in the calendar year 1996. Epoetin treatment was associated
with reduced mortality, with or without adjustment for co-morbid
conditions.
Fig. 6. Hospitalizations in 5302 patients from the Lombardy
Registry in the calendar year 1996. Higher haematocrits (Hct) were
associated with a reduced number of days in hospital per patientyear. (Adapted with permission from [28]).
34
J. F. E. Mann
incidence of stroke and acute MI after the introduction
of epoetin was not statistically significant. Furthermore, unlike the US and Italian studies, no attempt
was made to control for case mix. This may well
have changed during the study, with more elderly (and
therefore high-risk) patients being accepted for dialysis
as the study progressed. The underlying level of risk
in patients may, therefore, have been greater in the
latter part of the study, i.e. after epoetin was introduced, producing a false association between epoetin
treatment and increased mortality. This suggestion is
supported by the observation that among patients
suffering an acute MI, the mean age of the epoetin
users was slightly greater and the duration of dialysis
shorter. In addition, the duration of dialysis at the
onset of disease was longer in the post-epoetin period.
Effects of epoetin on quality of life
The quality of life of CRF patients is influenced by
many factors. Somatic symptoms and the restrictions
imposed by treatment usually interfere with work and
family life. Anaemia increases fatigue and reduces
physical working capacity, despite some physiological
adaptations to the lower oxygen transport capacity.
Quality of life is a complex concept. In its broadest
sense, it may include:
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individual factors (the patient’s own perception of
his or her quality of life)
family and social support
socioeconomic factors (income, work, education,
welfare system)
treatment factors (dialysis, other medical care,
psychosocial interventions, rehabilitation, patient
education).
Various instruments have been used in quality-oflife studies of CRF patients, ranging from objective
assessments of rehabilitation and functional capacity
to tools that concentrate on the patient’s own perception of well-being. In cost–utility studies, the total cost
of the intervention is related to the health gain of the
treatment. Both objective and subjective assessments
of quality of life are included in this kind of analysis.
Using a number of measures of quality of life,
epoetin treatment has been shown to improve patients’
sense of well-being, reduce fatigue, increase appetite
and work capacity, and improve exercise tolerance,
libido and work performance [30].
An open-label study by Evans et al. [31] of 300
epoetin-treated dialysis patients found a significant
improvement between baseline and follow-up (up to
16 months) in most objective and subjective qualityof-life parameters. These included: energy and activity,
functional ability, sleep and eating behaviour, disease
symptoms, health status, satisfaction with health, sex
life, well-being, psychological affect, life satisfaction
and happiness. No change was observed in ability to
work or employment status.
In another open-label study, Beusterien et al. investi-
gated 484 dialysis patients receiving epoetin for the
first time, with an average of 99 days’ follow-up. They
found significant improvements in vitality, physical
functioning, social functioning, mental health, looking
after the home, social life, hobbies and satisfaction
with sexual activity [32].
In a long-term study reported by Bárány et al. [33],
quality-of-life assessments were performed in 24
haemodialysis patients before epoetin treatment (mean
haemoglobin 7.3 g/dl ), after 2–10 months on epoetin
(mean haemoglobin 10.4 g/dl ) and after 12–22 months
on epoetin (mean haemoglobin 10.4 g/dl ). Correction
of anaemia brought about significant improvements in
quality of life that persisted for longer than 1 year.
The greatest changes occurred in satisfaction with
health, physical activity and emotional well-being.
There is no doubt that epoetin treatment improves
quality of life. The question, however, is whether the
extent of the improvement is related to the haemoglobin achieved on treatment. Probably the best controlled study of quality of life to date was the doubleblind, placebo-controlled, randomized trial performed
by the Canadian Erythropoietin Study Group [34].
The study included 118 haemodialysis patients aged
18–75 years, randomized to three groups: placebo (n=
40); epoetin to achieve a haemoglobin of 9.5–11 g/dl
(n=40); or epoetin to achieve a haemoglobin of
11.5–13 g/dl (n=38). The mean haemoglobin at 6
months was 7.4 g/dl in the placebo group, 10.2 g/dl in
the low haemoglobin group and 11.7 g/dl in the high
haemoglobin group.
Patients receiving epoetin were significantly less
fatigued, scored better on relationships, had less severe
physical symptoms and had moderate improvements
in exercise tolerance and depression compared with
patients not receiving epoetin ( Figure 7) [34]. The
quality-of-life scores did not differ significantly between
the high and low haemoglobin groups, which may
have been due to the relatively small differences in the
actual haemoglobin concentrations achieved in the two
epoetin treatment groups.
A more recent study, conducted in Spain by
Fig. 7. Effects of epoetin treatment on quality-of-life parameters in
the Canadian Erythropoietin Study Group study. Epoetin treatment
was associated with significant improvements in scores for physical
performance, fatigue, relationships and depression. (Data from [34]).
The short- and long-term consequences of anaemia in CRF patients
Fig. 8. Relationship between haemoglobin and Sickness Impact
Profile score in 1013 dialysis patients. Higher haemoglobin concentrations were associated with better quality-of-life scores. (Adapted
with permission from [35]).
Valderrábano’s group, has provided evidence that
greater improvements in quality of life are achieved at
higher haemoglobin values [35]. This cross-sectional
study evaluated quality of life in relation to haemoglobin in 1013 dialysis patients. Higher haemoglobin
concentrations were related to better quality-of-life
scores on the physical dimension and global score of
the Sickness Impact Profile (Figure 8) [35].
Epoetin treatment is clearly associated with improvements in various aspects of quality of life; further
studies are needed to determine at which haemoglobin concentration optimal results are achieved.
However, in order to maximize the beneficial effects of
treating anaemia, additional strategies must be implemented to improve the quality of life of CRF patients.
Such strategies include programmes for patient rehabilitation, education and exercise training.
Conclusions
This workshop aimed to summarize the current state
of knowledge on the short- and long-term consequences of anaemia in CRF patients, particularly
effects on the heart and quality of life.
The main effect of anaemia on the heart is an
increase in cardiac output. In the long term, this results
in the development of LVH and/or LV dilatation, and
a marked decrease in coronary reserve. Anaemia also
has vascular effects, including vasodilatation and
increased stiffness of the arterial wall, which possibly
lead to accelerated atherosclerosis. The end result of
these effects is an increase in mortality, especially
cardiovascular deaths. Moreover, as anaemia worsens,
the likelihood of frequent hospitalization and early
death increases.
Partial correction of anaemia with epoetin partially,
but not completely, reverses LVH. As LVH is a risk
factor for mortality, correcting anaemia with epoetin
should reduce premature deaths among CRF patients.
Support for this theory is provided by evidence from
a large prospective study, in which epoetin treatment
was associated with a 30% reduction in the crude
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relative risk of mortality. Furthermore, increasing
haematocrit/haemoglobin was associated with progressive reductions in the relative risk of general and
cardiovascular mortality, and the mean number of
hospitalizations.
It is evident that anaemia also has short-term,
adverse effects on quality of life, which can be improved
by correcting anaemia with epoetin. Although greater
improvements in quality of life have already been
demonstrated at higher haemoglobin concentrations,
further studies are needed to determine the level at
which optimal results are achieved.
The questions that still remain are:
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Does treating anaemia with epoetin reduce mortality and morbidity?
How early should treatment of anaemia be started
in CRF patients?
Should all subsets of patients with renal anaemia
be treated in the same manner?
Does full correction of anaemia have a more
beneficial effect than partial correction?
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