reviews

Cardiovascular disease in children with CKD

or eSrD
Marc R. Lilien and Jaap W. Groothoff
Abstract | Cardiovascular disease accounts for 40% of all deaths among pediatric patients with end-stage renal
disease (esrD). esrD has a particularly large influence on the cardiovascular system in children, as indicated
by the more than 700-fold increased risk of cardiac death in affected individuals compared with healthy
children of the same age. The prevalence of esrD is low in children, however, and, consequently, few cardiac
deaths occur. As a result, prospective follow-up studies of cardiac risk factors in the pediatric setting are
lacking. Nevertheless, cross-sectional data on cardiac disease in children with esrD have started to emerge.
Arterial medial calcification is more prominent in children than classic atherosclerotic intimal calcification.
Current data suggest that endothelial dysfunction appears early in renal failure in children, and is followed by
arterial medial calcification. This calcification causes arterial wall stiffening and subsequently left ventricular
hypertrophy. High systolic blood pressure and serum concentrations of intact parathyroid hormone, calcium
and phosphate, as well as long-term dialysis, seem to be important risk factors for cardiovascular disease in
pediatric patients with esrD. These features are important targets for preventive intervention. This review
summarizes the currently available data on cardiovascular disease in children with renal failure.
Lilien, M. r. & Groothoff, J. w. Nat. Rev. Nephrol. 5, 229235 (2009); doi:10.1038/nrneph.2009.10

Introduction Mortality and morbidity

Physicians who care for children with chronic
kidney disease (CKD) increasingly recognize that cardio
vascular disease is a major threat to their patients. several
reports have confirmed that, as in adults, cardiovascular
events are the main cause of death among patients who
develop endstage renal disease (esrD) in childhood.14 in
a statement by the american Heart association on cardio
vascular risk reduction in highrisk pediatric patients,
those with CKD were classified in the highest risk stratum,
alongside individuals with homozygous familial hyper
cholesterolemia, diabetes mellitus type 1, heart transplants
or coronary aneurysms due to Kawasaki disease.5
renal failure is associated with a cluster of classic risk
factors for cardiovascular disease. in addition, uremia
specific risk factors seem to contribute to cardiovascular
risk in this setting.6 in adults with renal failure, acceler
ated atherosclerosis leads to myocardial infarction and
contributes substantially to cardiovascular mortality. in
pediatric patients, risk factors for accelerated athero
sclerosis are present, but cardiovascular mortality is
largely the result of esrDspecific factors.
in this review, we discuss the arterial and cardiac
abnormalities found in children with CKD and esrD,
the potential determinants of these abnormalities, and
their prevention.
Competing interests
Mr Lilien has declared an association with the following
company: Ferring Pharmaceuticals. see the article online for full
details of the relationship. Jw Groothoff declared no competing
interests.
Complete and reliable data on the late outcomes of chil
dren with esrD are scarce (table 1). two studies on
mortality and causes of death in this setting reported
longterm followup data from patients who started
renal replacement therapy (rrt) during childhood, with
a mean followup of 9.7 and 16.0 years, respectively.1,2
in addition, oh et al.7 studied mortality and causes of
death among all 283 patients treated for esrD at a single
pediatric center. nearly 6% of this cohort was lost to
followup. Parekh et al.4 studied the causes of death of
1,380 patients included in the united states renal Data
system who started rrt before the age of 20 years and
died between 1990 and 1996, before the age of 30 years.
Chavers et al. 3 analyzed the causes of 107 deaths in
Department of Pediatric
medicare patients who started dialysis between 1991 and Nephrology, wilhelmina
1996, while under the age of 20 years. Childrens Hospital,
overall mortality in children with esrD is about 30 University Medical
Center, Utrecht,
times higher than that among children without esrD,1,2 The Netherlands
and the risk of cardiac death is more than 700fold (Mr lilien). emma
Childrens Hospital,
greater. 8 when hyperkalemia is excluded as a cause Academic Medical
of mortality, cardiovascular disease 1,2,4,7 and cardiac Center, Amsterdam,
death1,2,4 account for about 40% and 2030% of all deaths, The Netherlands
(JW groothoff).
respectively.1,2,4,7 uncertainty about the exact cause of
cardiac death in children with esrD is reflected by the Correspondence:
Mr Lilien, Department
high percentage of diagnoses of cardiac arrest (1352% of Pediatric Nephrology,
of all cardiac deaths, excluding cerebrovascular death wilhelmina Childrens
and hyperkalemia1,2,4). this apparently high incidence Hospital, University
Medical Center Utrecht,
of cardiac arrest might be caused by inaccurate labeling of room Ke 04.133.1,
myocardial infarction and/or arrhythmia due to myo PO Box 85090,
3508 AB Utrecht,
cardial hypertrophy. Cerebrovascular death occurred The Netherlands
in children on hemodialysis at higher rates in the early m.lilien@umcutrecht.nl

nature reviews | nephrology volume 5 | aPril 2009 | 229

2009 Macmillan Publishers Limited. All rights reserved

 reviews
Key points
Children with chronic kidney disease or end-stage renal disease have
an increased risk of cardiovascular death
sudden cardiac death is the most common cause of cardiovascular death
in children with renal failure
Arterial medial calcification (which increases arterial stiffness), left ventricular
hypertrophy and endothelial dysfunction are prevalent in children with renal failure
several modifiable factors predict cardiovascular abnormalities in children with
chronic kidney disease or end-stage renal disease, including hyperphosphatemia,
anemia, insufficient blood pressure control, high intake of calcium salts or active
vitamin D and high serum levels of intact parathyroid hormone
Transplantation and intensified hemodialysis regimens can minimize several
of the modifiable risk factors described above
era of rrt than it does now.1,2 although overall mortal
ity decreased during the first few decades of rrt, it has
stabilized since the early 1990s.1 risk factors for death
in children with esrD include dialysis (versus trans
plantation),1,2,4 sustained hypertension2 and young age
of onset of rrt.1,2,4 Black ethnicity is associated with an
increased risk of cardiac death.3,4
Chavers et al.3 also reported on 452 cardiovascular
events in 1,454 children (31%) with esrD. the overall
incidence of these events increased from 24.3% in the
04year agegroup to 36.9% in the 1519year age
group. arrhythmia was the most common cardiac event
(19.6%), followed by valvular heart disease (11.7%),
cardiomyopathy (9.6%) and acute cardiac death (2.8%).
From 1991 to 1996, the rate of cardiomyopathy increased
significantly (from 4.2 to 8.5 cases per 100 patientyears,
P = 0.003), but the rates of other cardiac events remained
unchanged. the design of this study precluded the authors
from providing an explanation for this phenomenon.3
Pathophysiology and risk factors
endothelial dysfunction, accelerated atherosclerosis, arte
rial stiffening due to vascular calcification, left ventricu
lar hypertrophy (lvH) and myocardial fibrosis can occur
simultaneously in adults with advanced renal disease. all
these abnormalities have their own determinants, and
they also strongly influence each others development.
endothelial dysfunction exacerbates arterial luminal
narrowing and arterial wall stiffening by allowing the
development of intimamedia thickening, medial hyper
trophy and calcification. these processes increase the
effect of specific renaldiseaseassociated risk factors for
vascular calcification. arterial wall calcification leads to
a loss of wall distensibility, which increases cardiac pres
sure load, and hence induces lvH. ultimately, lvH and
myocardial fibrosis can provoke sudden cardiac death by
arrhythmia or cardiac failure. Calcification of the cardiac
valves might further contribute to lvH. the combina
tion of lvH and accelerated atherosclerosis puts adults
with esrD at high risk of early myocardial infarction. in
this section, we discuss the roles and potential determi
nants of the abovementioned mechanisms in pediatric
renal failure.
230 | APRIL 2009 | voLume 5
2009 Macmillan Publishers Limited. All rights reserved
endothelial dysfunction
the endothelium is a key factor in the maintenance
of vascular tone and in prevention of thrombosis and
local inflammation of the vascular wall. endothelial
dysfunction is considered to be the initiating step in
the genesis of atherosclerosis and arteriosclerosis, 9
and such dysfunction predicts cardiovascular morbid
ity and mortality.10 in adults, endothelial dysfunction
appears early in renal disease and has been attributed
to a number of potential causes: reduced clearance of
the endothelial nitric oxide synthase (enos) inhibitor
asymmetric dimethyl arginine (aDma), which leads
to reduced bioavailability of endothelial nitric oxide;
activation of angiotensin ii, which induces oxidative
stress; high levels of homocysteine; chronic inflamma
tion; and dyslipidemia.11,12 impairment of endothelial
repair mechanisms might also contribute to endothelial
dysfunction. repair of damaged endothelium seems to
depend not only on resident cells in the vascular wall,
but also on bonemarrowderived circulating endothelial
progenitor cells (ePCs). low circulating numbers and
disturbed in vitro function of ePCs have been found in
adults with cardiovascular disease and in patients with
esrD.13 moreover, the number of circulating ePCs pre
dicts cardiovascular mortality in adults in the general
population.14 little is known about circulating ePCs in
children, although healthy children have higher numbers
of circulating ePCs than healthy adults, possibly as a
result of active growth.15 whether renal failure influ
ences ePC number and function in children remains to
be determined.
as in adults, endothelial dysfunction appears early
in renal disease in children, and has been observed in
children with conservatively treated CKD as well as
in children on dialysis and in those with a kidney trans
plant.1622 also as in adults, the accumulation of endo
genous inhibitors of enos seems to be responsible in
part for endothelial dysfunction.18,20 Data on the influ
ence of dialysis on endothelial function in adults are con
flicting, but in children, lilien et al.19 demonstrated that
flowmediated vasodilatation deteriorated acutely after
a hemodialysis session. resistance to growth hormone
might contribute to endothelial dysfunction in children,
as flowmediated dilatation also decreased after tempo
rary cessation of growth hormone therapy in children
with CKD.23
Atherosclerosis and vascular calcification
in adults with esrD, calcifications are found in both the
intimal and medial layers of the arterial wall. intimal
calcification is the result of advanced atherosclerosis,
which is characterized by the formation of irregular, calci
fied plaques and occlusive lesions. intimal calcification
is most commonly found in older patients with esrD.
By contrast, diffuse, nonocclusive, medial calcification
(monckebergs arteriosclerosis) is more dominant than
intimal calcification in young adults with esrD.24 medial
calcification increases arterial stiffness, and thus reduces
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Table 1 | Cardiovascular outcomes in children with chronic kidney disease or end-stage renal disease
Study Age at disease era of rrT Mortality and Causes of risk factors Comments
onset and onset and percentage of deaths cardiovascular
number of duration of due to cardiovascular death
patients (number follow-up causes
of deaths)
McDonald 020 years, 19622002, sMr 30a, 1.8 deaths 25% cardiac arrest, For death: era Complete follow-up of all
et al. n = 1,634 (436) mean of (95% Ci 1.52.1) per 16% CvA, 14% of esrD onset, patients in large database, but
(ANZDATA)1 9.7 years 100 patient-yearsa, 45% ischemia or Mi, 12% young age, no detailed data on calcium or
Cv death (40% after pulmonary edema, lack of phosphate levels or blood
exclusion of 11% hypertension, transplant pressure, and no check on
hyperkalemia) 22% other Cv causes cause of deaths
Parekh et al. 020 years, 19901996 1.913.6 cardiac deaths 7% Mi, 52% cardiac For cardiac very high number of patients but
(UsrDs)4 n = 1,380 (all (era of death), per 100 patient-years arrest, 16% death: older no reliable figures on relative
deceased until age depending on age, 23% cardiomyopathy, 17% age at death, influence of cardiac death and
patients) 30 years cardiac death (excluding arrhythmias, 8% other black ethnicity, no check on cause of death
cerebrovascular disease) transplant
overall
LeriC study2 015 years, 19721992, sMr 31, 1.5 deaths 58% CvA, 15% For death: age Dutch study with complete and
n = 249 (63) mean of (95% Ci 1.21.9) per congestive heart <6 years, start long follow-up of patients. Cause
16.1 years 100 patient-years, 41% failure, 12% ischemia of rrT in of death checked, but small
Cv death and/or Mi, 15% other 19721982, database, and no data on
(cardiac arrest 8%) dialysis, calcium or phosphate levels
hypertension
Oh et al.7 016 or 19701997, 5% mortality, 50% Cv Not reported Not reported single-center study. No exact
020 years, >15 years death data on cause of death, no
n = 283 (42) definition of CKD and high loss
to follow-up
Chavers 019 years, 19911996, 3.8 all-cause deaths per Not reported For death: Large database but incomplete
et al. n = 1,454 (107) 510 years 100 patient-years and young age data and short follow-up
(UsrDs)3 1.4 cardiac deaths per For cardiac
100 patient-years, 38% death: black
Cv death overall ethnicity
a
in patients with onset of rrT 19932002. Abbreviations: ANZDATA, Australia and New Zealand Dialysis and Transplant registry; CKD, chronic kidney disease; CvA, cerebrovascular accident;
Cv, cardiovascular; esrD, end-stage renal disease; Mi, myocardial infarction; rrT, renal replacement therapy; sMr, standardized mortality ratio; UsrDs, United states renal Data system.

the elasticity and compliance of arteries. this loss of
compliance increases systolic pressure, which leads to
lvH. the loss of compliance also increases the speed of
the arterial pulse wave, which travels from the aortic root
to the periphery and is reflected back to the heart during
diastole. normally, the reflected pulse wave increases
pressure in the coronary sinus and thereby improves myo
cardial perfusion. However, when the pulse wave velocity
(Pwv) is increased, the reflected wave arrives at the heart
before the end of systole, which increases the systolic
blood pressure and decreases the diastolic blood pres
sure. this increase in pulse pressure further contributes to
cardiac work load. Perfusion of the myocardium during
diastole is decreased, which contributes to myocardial
ischemia. increased Pwv is an independent predictor of
cardiovascular mortality in adults with esrD.25
intimal calcification is associated with classic risk
factors for atherosclerosis, such as age, diabetes melli
tus, smoking, high lDl cholesterol levels and inflamma
tion, whereas medial calcification is strongly associated
with esrDspecific factors, such as hypertension, long
term dialysis and use of calciumcontaining phosphate
binders. 24 High serum phosphate levels can induce
both intimal and medial calcification.24 a high serum
phosphate level has been associated with increased risks
of mortality and cardiac disease in adults, even in the
absence of renal disease.26 High extracellular phosphate
levels induce vascular smooth muscle cells to differentiate
into an osteoblastic phenotype that shows increased
expression of osteopontin and alkaline phosphatase.27,28
uremic serum might also, however, induce arterial
calcification and osteoblastic differentiation of vascular
cells in the absence of high phosphate levels.29 the factors
in uremic serum that could be responsible for medial
calcification and osteoblastic differentiation of vascular
cells are oxidative stress, parathyroid hormone (PtH)
fragments and vitamin D.12 PtH itself prevents vascular
calcification, but elevated levels of PtH fragments, many
of which are competitive inhibitors of the PtH receptor,
might increase vascular calcification.29
intimal disease, in the form of irregularly increased
carotid intimamedia thickness (cimt), can be detected
at an early stage by ultrasonography. medial disease is
characterized by an increase in Pwv, reduced carotid
wall elasticity (as assessed by mmode ultrasonography)
and a less pronounced increase in cimt with a more
regular pattern of thickening than is seen in intimal
disease. in 247 healthy adolescents aged 1020 years,
systolic blood pressure was the main predictor of
vascular stiffening, whereas cimt was only increased

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 reviews
in individuals with high pulse pressure and high body
weight, a wellestablished risk factor for atherosclerosis.30
increased cimt and carotid wall stiffening (as detected
by ultrasonography), as well as increased carotidfemoral
Pwv (as detected by applanation tonometry), all strongly
predict cardiovascular events in adults.31 increased arte
rial wall stiffening, as assessed by either Pwv or carotid
ultrasonography, is highly prevalent in children on
chronic dialysis.32,33 Data on cimt in children with esrD
are conflicting; most studies have reported significantly
increased cimt in children and young adults on rrt
compared with that in healthy controls, but some studies
found small or almost no increases in cimt.3336
in one study of children who had CKD or were on
dialysis, cimt was higher than in children who had a
renal transplant.35 cimt was independently associated
with factors related to calciumphosphate metabolism.35
on followup of the same children, cimt increased pro
gressively, but decreased after transplantation. 37 shroff
et al.33 found that cimt and aortic Pwv were normal
in children on dialysis who had well controlled serum
phosphate and intact PtH levels, but were increased in
those with high serum phosphate and intact PtH levels.
although occlusive atherosclerotic lesions are rare in
children, extensive coronary calcifications have been
observed in adolescents and young adults with esrD.7,38
Civilibal et al.39 found coronary calcification by use of Ct
in 8 of 53 (15%) patients with esrD aged 1121 years,
of whom 6 were on dialysis and 2 had a renal graft. all
the previously mentioned risk factorsparticularly high
serum phosphate level and high calcium and calcitriol
intakewere considerably more prevalent in patients
with coronary calcification than in those without.
Cardiac changes
lvH is caused by several conditions commonly found
in patients with CKD, including anemia, hypertension,
hypercirculation due to arteriovenous fistulae and
increased arterial stiffness. moreover, the structure of
the myocardium itself is altered in patients with esrD,
in a manner that is characterized by an increase in
interstitial fibrosis and a reduction in myocardial cap
illary density.40,41 these alterations influence the con
ductive properties of the myocardium and exacerbate
the risk of lifethreatening arrhythmias. lvH can be
either concentric (as a result of pressure overload from
increased systolic blood pressure and arterial wall stiff
ening) or eccentric (as a result of volume overload and
anemia). Both volume and pressure overload induce
myocardial remodeling by triggering events such as
the release of angiotensin ii and aldosterone, activation
of the sympathetic nervous system and inflammation.
this remodeling leads to predominantly diastolic dys
function and ultimately to systolic dysfunction, cardiac
failure and arrhythmia.
Circumstantial evidence of myocardial remodeling has
been found in children with esrD. Prolongation of the
Qt interval can occur during hemodialysis in children,
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2009 Macmillan Publishers Limited. All rights reserved
even without demonstrable electrolyte disturbances.42
Children with CKD have notably longer corrected Qt
intervals (Qtc) than healthy children and the duration
of the Qtc positively correlates with the duration of
renal failure.43 However, Qtc duration is not related to
left ventricular mass index,43 which implies that altera
tions of the myocardial tissue might contribute to the
increased risk of sudden cardiac death, independently
of lvH.
lvH, as assessed by ultrasonography, is a major risk
factor for acute cardiac death in adults with esrD, and
the most common cardiac abnormality in pediatric
patients with esrD.4446 Concentric lvH can be found
as early as stage 24 CKD in children.47 the incidence
of lvH at the onset of rrt varies from 54% to 82% in
children. 45,48,49 lvH improves in most children after
transplantation, provided that their blood pressure is
well controlled.49,50
as in studies of adults with renal failure, most studies
in children with renal failure show strong associations
between hypertension and lvH. other studies of the
relationship between blood pressure and lvH in chil
dren with conservatively treated renal failure report
conflicting results. in the esCaPe trial, no relationship
between blood pressure and lvH was found,51 but longi
tudinal studies that involved ambulatory blood pressure
measurement did show a relationship.48,52 therapeutic
goals for blood pressure control, which should prevent
lvH, are not always attained. Data from the Chronic
Kidney Disease in Children study (CKiD), which
enrolled patients with glomerular filtration rates of
3090 ml/min/1.73 m2, indicated that the overall preva
lence of hypertension was 54% and that 48% of patients
who were being treated for hypertension did not have
adequately controlled blood pressure.53
Therapeutic strategies
angiotensinconvertingenzyme (aCe) inhibitors
and angiotensin receptor blockers (arBs) can reduce
endothelial damage and are cardioprotective in adults
with CKD. Data from the CKiD study suggest that
use of aCe inhibitors and arBs is associated with
improved blood pressure control in children with CKD.51
supplementation of larginine, the substrate for produc
tion of nitric oxide by enos, might improve endothelial
function. However, Bennettrichards et al.54 found that
4 weeks of oral larginine supplementation had no effect
on endothelial function in children with CKD compared
with placebo, despite eliciting a substantial rise in plasma
larginine levels. although the same investigators did
demonstrate an improvement in flowmediated dilata
tion and a decrease in plasma homocysteine levels after
8 weeks of oral folic acid supplementation in children
with CKD, flowmediated dilatation was not different
between the actively treated group and the placebo group
at the same timepoint.55
as in adults, high serum levels of phosphate and of
calciumphosphate product are thought to be among the
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Table 2 | Mechanisms of and possible therapeutic measures for cardiovascular risk factors in children with renal failure
risk factor
Duration of CKD57
Time-averaged serum calcium
phosphate product35,36
Conventional dialysis vs
transplantation
Cumulative intake of calcium-based
phosphate binders35,36,57
Cumulative intake of calcitriol33
Current serum phosphate level57
Time-averaged serum intact PTH
level33
systolic blood pressure
Abbreviations: CKD, chronic kidney disease; PTH, parathyroid hormone.
pathophysiological possible therapeutic strategies
mechanisms
endothelial dysfunction, arterial intimal Prevent CKD
calcification, arterial medial calcification,
left ventricular hypertrophy and myocardial
remodeling, cardiac valve calcification
Arterial medial calcification, left ventricular reduce phosphate levels, consider
hypertrophy and myocardial remodeling, parathyroidectomy, avoid calcium-
cardiac valve calcification containing phosphate binders, consider
intensified (nocturnal) hemodialysis
endothelial dysfunction, arterial intimal Provide early transplantation, consider
calcification, arterial medial calcification, intensified (nocturnal) hemodialysis
left ventricular hypertrophy and myocardial
remodeling, cardiac valve calcification
Arterial medial calcification, left ventricular Administer calcium-free phosphate binders
hypertrophy and myocardial remodeling, (e.g. sevelamer)
cardiac valve calcification
Arterial medial calcification, left ventricular Avoid high calciumphosphate product
hypertrophy and myocardial remodeling, values
cardiac valve calcification
endothelial dysfunction, arterial intimal reduce dietary phosphorus intake,
calcification, arterial medial calcification, administer calcium-free phosphate binders
left ventricular hypertrophy and myocardial
remodeling, cardiac valve calcification
Arterial medial calcification, left ventricular Consider parathyroidectomy in cases of
hypertrophy and myocardial remodeling, high serum calcium and intact PTH levels
cardiac valve calcification
endothelial dysfunction, arterial intimal Administer intensive antihypertensive
calcification, arterial medial calcification, treatment
left ventricular hypertrophy and myocardial
remodeling, cardiac valve calcification

most important risk factors for vascular and cardiac valve
calcification in children with esrD. this observation
implies that vigorous treatment of hyperphosphatemia
with (preferably calciumfree) phosphate binders
is essential to prevent cardiovascular calcification.
although the evidence is less than convincing, some data
suggest that effective treatment of hyperparathyroidism
also prevents cardiovascular calcification.33
transplantation is associated with reductions in arte
rial stiffening and lvH, and it sharply reduces the risk
of cardiac death. BeckerCohen et al.49 found that the
prevalence of lvH decreased from 54% to 8% after trans
plantation in 13 children. nevertheless, cardiovascular
disease remains highly prevalent after transplantation
in children with esrD compared with in healthy chil
dren. in the leriC study, 75% of all men with juvenile
esrD who were aged 2040 years had functioning renal
allografts, and nearly 50% had apparent hypertension
associated lvH.50 Briese et al.56 found increased vascular
stiffness and signs of endothelial dysfunction in a study
of 36 children with renal transplants. Bilginer et al.57
found that cimt was increased in 24 renal transplant
recipients aged 924 years compared with that in healthy
controls; the extent of cimt increase was associated with
length of time on dialysis and the mean historical level of
calciumphosphate product.
left ventricular mass index improves in children over
a period of 2 years after commencing hemo dialysis,
in parallel with improvements in blood pressure and
volume control.45 intensified hemodialysis regimens,
especially quoti dian nocturnal hemodialysis, might
eliminate the majority of risk factors for cardiovascular
disease, by reducing serum aDma, phosphate, and
intact PtH levels, increasing HDl cholesterol levels
and normalizing mean blood pressure. in adults, noc
turnal hemodialysis is associated with disappearance
of lvH, improvement of endothelial function, restora
tion of impaired peripheral vascular flow and cessation
of vascular calcification.58 the very limited data on
this modality in children suggest the same beneficial
effects.59,60 in our experience, nearly all children feel
that the dramatic increase in wellbeing derived from
daily dialysis, especially under a nocturnal regimen,
by far compensates for the increased social burden.
in our opinion, such intensified hemodialysis regi
mens are mandatory for children who cannot undergo
transplantation immediately.
Conclusions
the risk of cardiovascular death is extremely high in
children with renal disease, and sudden cardiac death
is the main cause of cardiac death in these individuals.

nature reviews | nephrology volume 5 | aPril 2009 | 233

2009 Macmillan Publishers Limited. All rights reserved

 reviews

Classic risk factors for atherosclerosis are less prevalent
in children with esrD than in adults, which explains why
medial calcification is more apparent than intimal disease
in young patients. several modifiable risk factors, includ
ing hyperphosphatemia, hyperparathyroidism, anemia
and hypertension, independently predict the presence
of cardiovascular abnormalities in this setting (table 2).
increased awareness of the importance of controlling
these nontraditional risk factors, among physicians who
care for children with CKD or esrD could improve the
survival of these patients. new insights into the roles of
inflammation and microvascular function in cardio
vascular disease, the factors involved in the prevention
of metastatic calcification, the activities of circulating
ePCs, and novel treatment strategies for renal osteo
dystrophy might also contribute to improved survival.
large, prospective, international studies are warranted to
address these issues, and to provide improved treatment
options for this vulnerable population in the future.
Review criteria
Material for this article was retrieved by searching
PubMed using the terms (alone or in various
combinations) kidney failure, chronic Or end-stage
Or chronic AND kidney Or renal AND disease Or
failure AND myocardium Or cardiomyopathy
Or cardiac AND hypertrophy Or function Or
dysfunction Or arteriosclerosis Or arterial AND
compliance Or stiffness Or pulse wave velocity
Or intimamedia thickness Or endothelium AND
function Or dysfunction Or repair. results were
limited to studies that focussed on individuals aged less
than 18 years.

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