Editorial
The Effects of Frequent Hemodialysis on Left
Ventricular Mass, Volumes, and Geometry
Rakesh K. Mishra and Ruth F. Dubin
Clin J Am Soc Nephrol 8: 20252027, 2013. doi: 10.2215/CJN.10611013
Left ventricular (LV) remodeling is dened as the ge-
nomic expression resulting in molecular, cellular, and
interstitial changes that are manifested clinically as
changes in size, shape, and function of the heart after
cardiac injury (1). In ESRD, LV remodeling manifests
features of both concentric and eccentric LV hypertro-
phy, resulting from enlarged LV volumes and in-
creased LV wall thickness (2). As we discuss here, LV
mass can change because of a change in LV wall thick-
ness, LV cavity size, or both. Increased LV mass, in-
creased LV end-diastolic volume (LVEDV), and
changes in LV geometry (LV mass/LVEDV) are all as-
sociated with poor prognosis in these patients (3,4).
The Frequent Hemodialysis Network (FHN) trial is
the rst large-scale randomized controlled trial of fre-
quent daily and nocturnal dialysis versus conventional
dialysis (5). FHN investigators previously demon-
strated that, compared with conventional hemo-
dialysis, frequent daily hemodialysis results in a
signicantly greater reduction in LV mass, as deter-
mined by cardiac magnetic resonance imaging (MRI)
(6). In this issue of CJASN, this group reports that fre-
quent daily dialysis resulted in greater reductions in
LV and right ventricular (RV) volumes without signif-
icant changes in LV geometry (7). In addition, reduc-
tions in both LV mass and LVEDV with frequent
dialysis were signicantly correlated with reductions
in predialysis systolic BP (6,7). Here we present a brief
overview of the literature on the effects of dialysis on
LV remodeling, discuss likely mechanisms underlying
the ndings of the current study, and reect on impli-
cations for future investigation.
Observational studies of frequent dialysis have
shown salutary effects on BP (811) and LV mass index
(1215) and impressive survival rates (8,16). More-
over, LV hypertrophy has regressed in patients with
ESRD who have baseline LV hypertrophy when ag-
gressive management of BP and anemia was added
to a thrice-weekly dialysis regimen (17,18). One such
study shows that LV hypertrophy may regress with-
out a change in relative wall thickness, another mea-
sure of LV geometry (18). In several studies, including
the FHN trial, lowering BP was strongly associated
with regression of LV hypertrophy (9,10,1214). Prior
studies of frequent dialysis that evaluated LV size
in addition to mass did not specically address LV
geometry (10,13).
www.cjasn.org Vol 8 December, 2013
LV mass and volume are linked mathematically,
University of
physiologically, and empirically. Cardiac MRI is California, San
widely considered to be the gold standard for de- Francisco, San
termining LV volume and mass, while M-mode echo- Francisco, California;
cardiography overestimates LV mass in patients with and San Francisco
Veterans Affairs
ESRD undergoing hemodialysis because of its geo- Medical Center, San
metric assumptions (19). In cardiac MRI, LV mass is Francisco, California
calculated as myocardial volume multiplied by the
specic density of the myocardium (20). Myocardial Correspondence:
volume, in turn, is the difference between the end- Dr. Rakesh K. Mishra,
San Francisco
diastolic epicardial volume and end-diastolic endocar-
Veterans Affairs
dial volume, excluding the papillary muscles (LVEDV). Medical Center, 4150
Thus, while MRI-determined LV mass is free of geomet- Clement Street, Box
ric assumptions, it remains mathematically dependent 111C, San Francisco,
on LV cavity size (LVEDV). This dependence of MRI- CA 94121. Email:
rakesh.mishra@ucsf.
determined LV mass on LVEDV has been conrmed edu
empirically in patients with ESRD receiving hemodial-
ysis (21). The strong correlation between LV mass and
LVEDV in ESRD reects the fact that LV hypertrophy is
an adaptive response, at least in part, to chronic volume
overload. In this issue of CJASN, this relationship be-
tween LV mass and LVEDV was reected in the nding
that most participants receiving frequent dialysis had
reductions in both LV mass and LVEDV (Figure 4 in Chan
and colleagues article) (7).
However, the ndings of the current study suggest
that the reduction in LVEDV is not purely the result of
more effective management of cyclic changes in blood
volume by frequent dialysis. Within the frequent dialy-
sis group, interdialytic weight gain was associated
with neither changes in LV mass (6) nor changes in
LVEDV (7). These ndings are similar to those of an
earlier study that found no signicant correlation be-
tween changes in total volume and changes in LVEDV
(22). On the basis of this nding, we propose that
changes in LVEDV induced by hemodialysis may
not be related solely to changes in total blood volume,
which would be reected in changes in the interdia-
lytic weight; decreased LVEDV may also result from a
peripheral relocation of the blood volume away from
the heart.
With frequent dialysis, there was a proportional
decrease in both stroke volume (change, 210.58%) and
LVEDV (change, 211.19%) (Table 2 in Chan and col-
leagues article) (7). Although this means that LV ejec-
tion fraction (stroke volume/LVEDV) did not change,
we may infer that stroke work (stroke volume3LV
Copyright 2013 by the American Society of Nephrology 2025
2026 Clinical Journal of the American Society of Nephrology
systolic BP) decreased in the daily dialysis group (as op-
posed to the conventional group, in which stroke volume
did not change) (Table 2 in Chan and colleagues article).
Stroke work is the primary determinant of myocardial oxy-
gen consumption. Therefore, the reduction in stroke work
induced by frequent daily dialysis may lead to decreased
myocardial oxygen consumption (2). Decreased myocardial
oxygen demand, in turn, may improve myocardial oxygen
supply-and-demand balance and may render the heart less
vulnerable to ischemia-induced myocyte injury and ven-
tricular arrhythmias. This is supported by results from a re-
cent observational study showing reduced prevalence of
myocardial stunning among patients receiving frequent
dialysis (23).
The proportionate decrease in LV mass and LVEDV seen
in the study by Chan et al. results in unchanged LV geome-
try. However, there are additional ways to evaluate LV re-
modeling. In a different study, Chan et al. examined gene
expression in rat cardiomyocytes treated with plasma from
patients who had undergone nocturnal or conventional di-
alysis. Cardiomyocytes treated with plasma from nocturnally
dialyzed patients showed downregulation of proapoptotic
and brotic genes, and upregulation of genes encoding pro-
teins of cardiac contractility (24). In this same study, echocar-
diographic velocity vector imaging of patients on nocturnal
dialysis showed better circumferential strain and torsion, sug-
gesting improved LV systolic function (24). Future studies
evaluating changes in gene expression, novel serologic bio-
markers, or functional measures of LV performance may
shed light on the effect of therapies aimed at reversing LV
remodeling.
In addition to stratifying by LV mass, it might be useful to
stratify future analyses by baseline LV geometry. In ESRD,
LV mass/LVEDV may have opposite associations with prog-
nosis, depending on whether the LV is dilated or not (4). In
patients with a dilated LV, lower LV mass/LVEDV is associ-
ated with a worse prognosis; conversely, in those with normal
LV cavity size, higher LV mass/LVEDV is associated with
worse prognosis. In the former group, there is probably in-
sufcient adaptive wall thickening to offset the higher LV wall
stress of a dilated ventricle. Moreover, it remains uncertain
whether patients with normal LVEDV at baseline benet
from further reduction in LVEDV; it is likely that in such pa-
tients, LV mass, not further reduction in LV volumes, would
be associated with improved outcomes. In this issue of CJASN,
it would have been interesting to test for a difference in the
1-year change in LV volumes between participants with di-
lated left ventricles at baseline and those with LV volumes in
the normal range.
In comparison to the LV, the RV suffers from relative ne-
glect in various pathologic states, such as congestive heart
failure and ESRD. RV dysfunction is prevalent among pa-
tients with ESRD receiving hemodialysis (25). RV overload
and dysfunction may contribute to LV dysfunction through
interventricular dependence (26). The current study in this
issue of CJASN is the rst to report on the benecial effect of
frequent daily hemodialysis on RV end-diastolic volume
(RVEDV) and, to a lesser extent, on RV end-systolic volume.
Unlike changes in LVEDV, reductions in RVEDV were as-
sociated with both reductions in predialysis systolic BP and
lower interdialytic weight gain. It is interesting to note that
in this study, even conventional dialysis led to signicant,
but more modest, reductions in RVEDV and RV end-systolic
volume. Although LV ejection fraction did not signicantly
change with frequent hemodialysis in this study, it would be
interesting to investigate whether alleviating RV overload
contributes to improved LV systolic and diastolic function
as measured by advanced imaging techniques, such as LV
myocardial strain or torsion (27,28).
In summary, ndings from the FHN trial show that fre-
quent hemodialysis results in reductions in LV mass and
volumes and that these reductions are signicantly corre-
lated with reductions in predialysis systolic BP. The current
study in this issue of CJASN enhances our understanding
of the effects of frequent dialysis on the heart by providing
a comprehensive evaluation of left and right ventricular
volumes and of LV geometry. The implications of these
changes in cardiac structure induced by frequent dialysis
for LV diastolic function and susceptibility to myocardial
injury are directions for future research.
Disclosures
None.
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Published online ahead of print. Publication date available at www.
cjasn.org.
See related article, Effects of Frequent Hemodialysis on
Ventricular Volumes and Left Ventricular Remodeling, on pages
21062116.