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NATURE REVIEWS | NEPHROLOGY VOLUME 8 | MARCH 2012 | 163
Division of Nephrology, Department of Internal Medicine, Yonsei
University College of Medicine, 50 Yonsei-ro Seodaemun-gu, Seoul
120-752, Korea (S.H.Han, D.S. Han).
Correspondence to: D.-S. Han [email protected]
Nutrition in patients on peritoneal dialysisSeung-Hyeok Han and
Dae-Suk Han
Abstract | Proteinenergy wasting (PEW) is prevalent among
patients on dialysis and has emerged as an important risk factor
for morbidity and mortality in these patients. Numerous factors,
including inflammation, inadequate dialysis, insufficient nutrient
intake, loss of protein during dialysis, chronic acidosis,
hypercatabolic illness and comorbid conditions, are involved in the
development of PEW. The causes and clinical features of PEW in
patients on peritoneal dialysis and hemodialysis are comparable;
assessment of the factors that lead to PEW in patients receiving
peritoneal dialysis is important to ensure that PEW is managed
correctly in these patients. For the past 20years, much progress
has been made in the prevention and treatment of PEW. However, the
results of most nutritional intervention studies are inconclusive.
In addition, the multifactorial and complicated pathogenesis of PEW
makes it difficult to assess and treat. This Review summarizes the
nutritional issues regarding the causes, assessment and treatment
of PEW, with a focus on patients receiving peritoneal dialysis. In
addition, an in-depth overview of the results of nutritional
intervention studies is provided.
Han, S.-H. & Han, D.-S. Nat. Rev. Nephrol. 8, 163175 (2012);
published online 7 February 2012; doi:10.1038/nrneph.2012.12
Introduction Dialysis is now established as a successful therapy
for the management of patients with end-stage renal disease (ESRD).
To further improve patient outcomes, much emphasis has focused on
optimizing the adequacy of dialysis, managing blood pressure and
anemia and maintaining biochemical parameters within the target
range. When compared with these issues, however, the importance of
proteinenergy wasting (PEW) seems to be underestimated. Although
much progress has been made in improving the nutritional status of
patients, the prevalence of PEW in patients on dialysis remains
high, ranging from 18% to 56%, depending on the assessment methods
used.15 Accumulating evidence indicates that PEW is an important
predictor of morbidity and mortal-ity in patients on dialysis and
impairs quality of life.69 Constant monitoring of nutritional
status and early detection, as well as therapeutic strategies for
the preven-tion and treatment of PEW, are therefore crucial in the
management of patients on dialysis. A number of tools are widely
used in clinical practice for the assessment of PEW, yet no single
method comprehensively reflects nutritional status, which should be
cautiously assessed in combination with other clinical and
biochemical para-meters. Of note, however, no data have
convincingly demonstrated that improving PEW has a marked effect on
morbidity or mortality of patients.
The causes and features of PEW in patients on dialysis are
similar between those on hemodialysis and perito-neal dialysis10
and include inflammation, inadequate protein and calorie intake,
loss of appetite, loss of resid-ual renal function (RRF), loss of
protein during dialysis, psychosocial factors, physical inactivity
and comorbid
conditions.1114 Another important factor to note is that
peritoneal dialysis itself could suppress appetite.13,15 With these
factors in mind, pertinent issues such as the causes, pathogenesis,
assessment and treatment of PEW in patients on peritoneal dialysis
are reviewed here.
Nomenclature Malnutrition literally means bad nutrition and is
usually considered to entail undernutrition, which is
character-ized by low food intake and a modest decrease in serum
albumin levels; undernutrition can be corrected by increasing
nutrient intake. In patients with ESRD, this form of malnutrition
is sometimes termed type1 mal-nutrition.16 Another type of
malnutrition also exists in which an inflammation-associated
wasting process is involved. However, differentiating between these
two types of malnutrition is difficult and the majority of patients
on dialysis have both. To date, multiple terms have been used
(often interchangeably and confusingly) to describe malnutrition in
patients with ESRD, includ-ing uremic malnutrition, uremic
cachexia, proteinenergy malnutrition, malnutrition inflammation
athero sclerosis (MIA) syndrome and malnutritioninflammation
complex. Moreover, multiple conditions in patients with chronic
kidney disease (CKD), such as inflammation, nutrient loss during
dialysis, chronic acidosis, hypercatabolic illness, and endocrine
dis-orders including resistance to insulin, growth hormone, and
insulin-like growth factor (IGF)-I can cause loss of muscle mass
despite adequate nutrient intake.5,13 As the altered nutritional
status associated with these condi-tions is not solely attributed
to reduced nutrient intake, it cannot be corrected merely by
increasing intake.
To avoid confusion, the term PEW was proposed by a panel of
experts from the International Society of Renal
Competing interestsThe authors declare no competing
interests.
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Nutrition and Metabolism (ISRNM),4 and is steadily gaining
acceptance. According to the ISRNM, PEW is the state of decreased
body stores of protein and energy fuels (that is, body protein and
fat masses). PEW is character ized by markedly decreased serum
albumin levels, the presence of inflammation and oxidative stress
and greater levels of protein breakdown than synthesis. A reduced
muscle mass seems to be the most valid cri-terion for the presence
of PEW. In addition, the ISRNM panel recommends that cachexia is
differentiated from PEW and used to denote a severe form of PEW,
often associated with profound physiological, metabolic, psycho
logical and immunological disorders.4 Based on the suggestion by
the ISRNM panel, in this Review we use the term PEW instead of
malnutrition to avoid prob-lems in interpretation when nutritional
problems occur in patients with CKD.
Causes and pathogenesis of PEW Inflammation In patients with
ESRD, inflammation is common and leads to atherosclerosis and
arteriosclerosis, which eventually results in increased
cardiovascular morbid ity and mortality. Moreover, elevated levels
of C-reactive protein (a serum inflammatory marker) predicts mortal
ity independently of other comorbidi-ties in patients on peritoneal
dialysis.17 Inflammation, alone or in combination with other
factors, also has a key role in the pathogenesis of PEW. Indeed,
malnutri-tion (that is, PEW), inflammation and atherosclerosis
coordinate together in a vicious cycle of so called MIA syndrome16
and have been associated with high rates of morbidity and
mortality. In particular, the 2-year mortal ity rate increased up
to 70% in patients who had all three components of MIA syndrome
compared with approximately 10% or less in patients who had none of
these components.18,19
Several mechanisms have been proposed to explain how
inflammation is involved in PEW. First, pro-inflammatory cytokines
could cause muscle wasting by
Key points
Proteinenergy wasting (PEW) is common and is an important risk
factor for morbidity and mortality in patients on dialysis
Inflammation, inadequate dialysis, insufficient nutrient intake,
loss of protein during dialysis, chronic acidosis, hypercatabolic
illness, comorbid conditions, psychosocial factors and physical
inactivity are involved in the development of PEW
Peritoneal dialysis itself might lead to PEW as continuous
glucose absorption from peritoneal dialysis solutions, abdominal
fullness induced by the dialysate and peritonitis can suppress
appetite
No single test is precisely indicative of PEW; comprehensive
diagnostic criteria for PEW proposed by the International Society
of Renal Nutrition and Metabolism could be useful
A number of treatment options for PEW are available but
improving nutritional status is difficult and no data have
convincingly shown that nutritional intervention improves patient
survival
A multidisciplinary approach to PEW management should be
provided by providing nutritional assessment and support, dietary
counseling, management of comorbid conditions, and by maintaining
an adequate dialysis dose and preserving residual renal
function
increasing protein hydrolysis and muscle-protein break-down
through activation of the ubiquitinproteasome proteolytic pathway
or nuclear factor B signaling.20 In addition, inflammation can
suppress appetite and induce anorexia. In fact, elevated plasma
levels of tumor necrosis factor were found in patients with
anorexia on peritoneal dialysis compared with levels in patients
without anorexia.21 Inflammation-associated anorexia was reported
to be mediated by leptina hormone that suppresses appetite. Indeed,
blocking leptin signal-ing through the hypothalamic melanocortin 4
recep-tor improved uremic cachexia in a mouse model.22 Furthermore,
visfatin, a newly identified adipocyte-derived factor that is
sensitive to inflammation, might also contribute to uremic
anorexia.23
A second mechanism involves insulin resistance. Insulin is an
anabolic hormone that exerts anticatabolic effects on skeletal
muscle.24 Inflammatory cytokines disturb insulin signaling
pathways, which results in decreased insulin sensitivity.25 This
effect, in turn, might dampen the anabolic effect of insulin on
skeletal muscle and cause loss of muscle mass. Indeed, insulin
resistance correlated with muscle wasting in 21 patients on
perito-neal dialysis,26 which suggests that insulin resistance is
closely linked with PEW.
Other peritoneal dialysis-related factors that might cause
inflammation include poor oral health, volume overload,
peritonitis, and bioincompatible solutions;2729 of note, these
factors (unlike those discussed above) are potentially reversible.
In fact, when the uid status of 25 patients on peritoneal dialysis
was well-controlled, nutri-tional status and inflammation were
improved, whereas fluid overload resulted in worse nutritional
status and promoted inflammation.28
Inadequate nutritional intake The Kidney Dialysis Outcomes
Quality Initiative (KDOQI) guidelines recommend a daily energy
intake of 35 kcal/kg for patients on peritoneal dialysis 60years
and daily protein intake of 1.21.3 g/kg.30 However, a large
proportion of patients on peritoneal dialysis ingest a considerably
lower amount of calories and protein than the recommended
amounts.31,32 Moreover, inadequate dietary protein intake (DPI) is
associated with increased all-cause and cardiovascular mortality in
these patients.9 Despite inadequate protein or energy intake, one
study showed that glucose absorption from the dialysate can provide
some energy33 and another study demonstrated that the nitrogen
balance in the majority of patients on peritoneal dialysis is
positive.34
Nutrient intake by patients on dialysis can be influ-enced by
many factors: inflammation, taste abnormali-ties, gastrointestinal
problems, medications, physical inactivity, dietary restrictions,
emotional and psycho-logical disorders and social constraints such
as poverty (Figure1).3537 Factors that are specific to peritoneal
dialysis might also be associated with poor oral intake as
continuous absorption of glucose from peritoneal dialy-sis
solutions15,38 and abdominal fullness induced by the
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NATURE REVIEWS | NEPHROLOGY VOLUME 8 | MARCH 2012 | 165
dialysate13 can cause loss of appetite. Interestingly, gastric
emptying was delayed in patients receiving peritoneal dialysis.39
However, whether this delay is attributed to dialysate dwell perse
or to the absorption of substrate substances with caloric and
metabolic activity such as glucose is uncertain.40
Ghrelin, a gut peptide that regulates hunger by stimu-lating
neuropeptide Y and agouti-related peptide in the hypothalamus, has
been identified as an appetite enhancer.41 Paradoxically,
circulating ghrelin levels were increased in patients on dialysis
when compared with levels in healthy controls,42 which suggests
that these patients are resistant to ghrelin. Nevertheless, plasma
ghrelin levels were markedly lower in anorexic patients on
peritoneal dialysis than in those with normal appe-tite.43
Interestingly, as exchange with peritoneal dialysis solution lowers
ghrelin levels,44 a reduced level of ghrelin might mediate this
anorexic effect.
Bioincompatibility of peritoneal dialysis solu-tion might also
influence appetite: in a rat model, a bicarbonate lactate solution
suppressed appetite to a lesser extent than a lactate solution.45
No clinical evidence, however, exists to support this finding.
Loss of nutrients into dialysate Although waste products are
cleared during dialy-sis treatment, nutrients are also lost into
the dialysate. Patients on peritoneal dialysis lose approximately
912 g of total protein and 68 g of albumin daily.5,46 Loss of
protein is much greater during an episode of perito-nitis.46 In
particular, the type of peritoneal membrane transport might
influence the amount of protein loss. In patients with a fast
peritoneal solute transport rate (that is, high transporters),
protein losses are consider-ably greater than in patients with a
low solute transport rate.47 Relevant to this finding is our
observation that a fast peritoneal solute transport rate is
independently associated with poor nutritional status in patients
on peritoneal dialysis.48 Fast peritoneal solute transport rates
have also been associated with inflammation49 and mortality in some
studies;50,51 however, other studies have found no association
between peritoneal transport rate and nutritional status.52,53 Of
note, high risk of adverse outcomes in high transporters was only
observed in those on continuous ambulatory peritoneal dialysis; no
relationship between peritoneal transport rate and either mortality
or transfer to hemodialysis has been reported for patients
receiving automated peritoneal dialysis.54,55 In addition, inherent
fast transport (that is, when the patient has a fast solute
transport rate from the start of peritoneal dialysis) and acquired
fast transport (that is, when the transport rate increases with
time on peritoneal dialysis) might have different clinical
implications; inher-ent fast transport is associated with increased
mortality because it is linked with greater levels of comorbidity
and inflammation than acquired fast transport.56 Such discrepancy
between findings regarding the relationship between peritoneal
transport types and nutritional status can be explained by
differences in study design, number of enrolled patients, patient
characteristics, the
timing of evaluation of peritoneal transport type and
nutritional assessments. Further investigations using more detailed
methods such as the diagnostic criteria proposed by the ISRNM panel
are required to delineate the association between peritoneal
transport types and nutritional status.
Loss of residual renal function Over the past 20years, the
importance of preserving RRF has been highlighted in many aspects
of the management of patients on dialysis and low RRF is an
independent risk factor for adverse outcomes in these
patients.12,57 From a nutritional viewpoint, numerous reports have
indicated that RRF is also important in determining nutritional
status. In one study, preserved RRF was independently associated
with a greater intake of dietary protein, calories and other
nutrients, whereas peritoneal dialysis solute clearance was not.11
In addition, resting energy expenditure was found to be inversely
correlated with RRF, which suggests that patients with decreased
RRF have an altered protein metabolism.58 Furthermore, a number of
studies have shown that patients with pre-served RRF have a better
nutritional status, as deter-mined using different assessment
methods such as lean body mass (LBM), normalized protein catabolic
rate (nPCR), subjective global assessment (SGA) score, DPI, serum
albumin level, and handgrip strength than patients who have low or
no RRF.11,5961 Moreover, loss of RRF is associated with increased
systemic inflam-mation.62 Given the importance of inflammation as a
key mediator of muscle wasting and anorexia, loss of RRF can be
presumed to contribute to PEW through exacerbated inflammation.
A decrease in middle molecule clearance is also clearly evident
as RRF declines63 and this effect might adversely affect
nutritional status. Whether increasing the removal of middle
molecules improves nutritional status, however, remains to be
further explored as their increased removal by high-flux dialysis
failed to improve nPCR in patients on hemodialysis.64
Factors related to uremia Factors related to peritoneal
dialysis
Inammation
Anorexia
Hypercatabolism
Chronic acidosis
Comorbid conditions:diabetes mellitus,
cardiovascular disease,infection
Inadequatenutrient intake
Inadequate dialysis
Loss of nutrientsinto dialysate
Appetite loss due toglucose absorption
from dialysate
Peritonitis
Bioincompatiblesolution?
Abdominal discomfortinduced by dialysate
Loss of residualrenal function
Proteinenergywasting
Figure 1 | The causes of proteinenergy wasting in patients on
peritoneal dialysis.
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Hypercatabolic statePatients with PEW on dialysis are
characterized by a hypercatabolic state that is promoted by
numerous factors including inflammation, negative protein and
energy balance during dialysis, diabetic complications, concurrent
infection or sepsis, comorbid conditions such as cardiovascular
disease, acidosis and resistance to IGF-I and growth hormone.37
Possible mechanisms of acidosis-induced PEW are protein
degradation, protein breakdown from skel-etal muscle and oxidation
of branched-chain amino acids,65 a decrease in albumin synthesis,66
and reduced expression of IGF-I and growth hormone.67 Many
cross-sectional studies have shown a direct relationship between
the severity of metabolic acidosis and nutri-tional status in
patients with CKD.68 We observed that patients on peritoneal
dialysis with serum bicarbonate levels of 1820 mmol/l (associated
with mild to mod-erate acidosis) had a favorable nutritional
status.69,70 However, detailed analysis revealed that patients with
severe metabolic acidosis (that is, serum bicarbonate levels
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NATURE REVIEWS | NEPHROLOGY VOLUME 8 | MARCH 2012 | 167
sensitive marker of nutritional status than albumin. However,
prealbumin can also be lost into dialysates and its levels in serum
are higher in patients on peritoneal dialysis than in those on
hemodialysispossibly owing to the increased hepatic synthesis in
response to its peritoneal loss.76
Body mass Epidemiological studies indicate the presence of an
obesity paradox (that is, a high BMI is associated with survival)
in patients on maintenance dialysis.77 Indeed, in patients on
hemodialysis and peritoneal dialysis, a low BMI is associated with
an increased risk of mor-tality.78,79 However, BMI can be affected
by fat mass or hydration status. In particular, peritoneal dialysis
often leads to greater volume expansion than hemodialysis,80 which
suggests that BMI might not be a useful parameter of nutritional
status in patients on peritoneal dialysis. Interestingly, the
survival advantage associated with a higher BMI is less apparent in
patients on peritoneal dialysis than in those on hemodialysis.79,81
Furthermore, the majority of studies that show this obesity paradox
in patients on dialysis were conducted in the USA. In fact, obesity
was associated with worse outcomes in a study of patients on
peritoneal dialysis in Australia and New Zealand;82 an analysis
that pools patients on hemo dialysis and peritoneal dialysis might
not, therefore, be appro-priate. Defining BMI as indicative of PEW
in patients on peritoneal dialysis might need to be individualized
depending on the patient population.
Muscle mass Muscle wasting is a key feature of PEW. In fact, a
reduced muscle mass with high BMI (so-called sarcopenic obesity)
was associated with inflammation and increased mortality in
patients with ESRD, although the patients with these
characteristics were indeed obese as assessed by BMI.83,84
Anthropometric assessment of mid-arm muscle circumference is
commonly used to measure muscle mass. However, this method can be
insensitive as it is associated with a substantial interobserver
error and is affected by hydration status.13 As for BMI,
interpreta-tion of parameters of muscle mass in patients on
perito-neal dialysis should be made after a careful considera tion
of fluid status.
Dietary intake Dietary intake as assessed by dietary diaries and
inter-views, even when a dietitian is involved, can be subjec-tive
and inaccurate. The accuracy of determining dietary intake depends
on the reliability of patients to properly quantify the amount of
food eaten.85 In fact, in a study of 40 patients on peritoneal
dialysis, a significant number of patients (particularly those who
were overweight) were found to under-report energy intake as
evaluated by 3-day food diaries.86 In addition, estimation of DPI
using a urea kinetic model can be unreliable in patients who are in
anabolic or catabolic states and can be confounded by the
concomitant loss of protein into, or energy intake from, the
dialysate.85
The ISRNM panel recommended other potential tools for assessment
of PEW that include scoring systems such as the SGA score and
malnutritioninflammation scoreboth of which are widely used in
clinical practice. However, the accuracy of these scoring systems
depends on the examiner and considerable training is required to
ensure consistent and steady results. In addition, no consensus has
been reached on the relationship of these subjective assessments in
the diagnosis of PEW.4
Prevention and treatment of PEW As PEW is multifactorial in
origin, a single therapeutic strategy is unlikely to be successful.
Although a number of treatment options are available, restoring
normal nutritional status in patients with PEW on dialysis is
difficult and no data exist that convincingly show that nutritional
intervention improves patient survival. Here, we provide an
overview of the management of PEW in patients on peritoneal
dialysis.
Dialysis dose Accumulation of uremic toxin with CKD progression
is associated with anorexia.87 In clinical practice, patients with
anorexia commonly regain appetite after dialysis is initiated;
however, whether increasing dialysis dose leads to better clinical
outcomes is still debated. Observational studies have suggested a
link between dialysis adequacy and nutritional status;8,11,88
however, although several prospective longitudinal studies have
investigated whether increasing dialysis dose improves nutritional
status in patients on peritoneal dialysis,8993 the results of these
have been inconclusive and limited by short follow- up duration and
small sample size. In one of these studies, an increase in
dialysis-derived calories and cre-atinine appearance, as well as
stabilization of weight and mid-arm circumference, was observed in
malnourished patients after dialysis dose was increased.93
Objective measures of improvement, such as increased serum albumin
level, were marked in patients without comorbid disease. By
contrast, other studies found no improvement in either serum
albumin level or normalized protein nitrogen appearance (nPNA)
despite an increase in Kt/V.89,92 Moreover, secondary analyses of
the Adequacy of Peritoneal Dialysis in Mexico (ADEMEX) trial94 and
of an interventional study conducted in six centers in Hong Kong95
found no association between higher dialy-sis dose and improved
nutritional status. To date, only one prospective, randomized study
has investigated the link between dialysis dose and nutritional
status; increas-ing Kt/V from 1.82 to 2.02 over 12months resulted
in an increase in nPNA from 1.10 g/kg to 1.24 g/kg, whereas no
improvement was observed in serum albumin level, SGA score, LBM or
DPI.96 Interestingly, reports have suggested that the relationship
between Kt/V and nPNA is not linear but reaches a plateau at a
weekly Kt/V of approximately 1.8.9799 This finding is in line with
the secondary analyses of the ADEMEX trial and Hong Kong study.
Depending on the baseline dialy-sis dose, therefore, increasing the
dialysis dose could improve nutritional status in some patients.
However,
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the effects of increments beyond a certain point seem to be
attenuated.
If underdialysis is suspected in patients with anorexia and
declining nutritional status on peritoneal dialysis, the dialysis
dose should be increased to optimize dialy-sis adequacy.
Alternatively, combined peritoneal dialysis and hemodialysis
therapy might be helpful in improv-ing nutritional status. Indeed,
nPNA, creatinine genera-tion rate and LBM significantly increased
after adding a once weekly hemodialysis session to 56days per week
of peritoneal dialysis regimen in patients affected by
underdialysis or fluid overload.100
Preservation of RRFAs loss of RRF is associated with
deterioration in nutri-tional status, preservation of RRF could be
assumed to maintain nutritional status. Prospective, random-ized
intervention studies are not feasible, however, as RRF declines
over time. Moreover, RRF is influenced by many factors and cannot
be easily manipulated. One study showed a marked decline in the
nutritional status of patients on peritoneal dialysis who lost
RRF.93 Furthermore, RRF had a considerable effect on nutri-tional
status as nutritional intake was affected to a greater extent by
RRF than by peritoneal dialysis solute clear-ance,11 which supports
the findings from a previous study.101 Given the large contribution
of RRF to nutri-tional status and patient outcome, various efforts
to pre-serve RRF in patients on dialysis should be an essential
part of PEW prevention strategies.
Dietary counselingIn patients on peritoneal dialysis, regular
and compre-hensive assessments to identify factors that cause PEW
are mandatory. Of note, only 39% of 266 patients on peri-toneal
dialysis complied with a DPI of 1.2 g/kg per day as recommended by
the KDOQI guidelines.102 Therefore, dietary counseling might be
useful if inadequate nutri-tional intake is a problem. Indeed, a
marked improve-ment in nutrient intake and in grades of
malnutrition was observed in 283 patients on peritoneal dialysis
after repeated dietary counseling.103 However, the results of two
prospective studies were inconsistent with each other.104,105 In
particular, a randomized, controlled trial that included 54
patients on peritoneal dialysis demon-strated that a substantial
proportion of these patients were unable to increase protein and
energy intake over 4 months, even though dietary advice was
provided.105
Although DPI 1.21.3 g/kg per day is generally recom-mended for
patients on peritoneal dialysis, the optimal target has not yet
been determined. In fact, the European guidelines suggest a protein
intake 1.0 g/kg per day106 and a study of Chinese patients on
peritoneal dialysis showed that DPI >0.94 g/kg per day was
associated with favorable nutritional status and long-term
outcomes.9 Interestingly, both this study and the European
guide-lines warned against lower DPIs of
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proteins into the dialysate.5,46 One exchange with a 1.1% amino
acid solution can compensate for these losses and meet the
nutritional requirements in patients on peri-toneal dialysis. A 6 h
dwell time with a 1.1% amino acid solution enables approximately 16
g (7278%) of amino acids to be absorbed, which is greater than the
peri-toneal loss of amino acids using conventional glucose
solutions.123 Anabolic effects are also induced as muscle protein
synthesis and IGF-I levels are increased, which reduces muscle
protein breakdown.124 The results from some studies support the use
of an amino acid-based dialysis solution in patients with PEW, as
they have demonstrated improvement in several biochemical and
anthropometric nutritional parameters and a positive nitrogen
balance (Table2).125134 However, these find-ings are not consistent
with those from other studies (Table3).135139 Our long-term
observations, however, support the use of amino acid-based dialysis
solutions, as daily use of an amino-acid based solution for 12
months resulted in significant increases in nutritional
para-meters, including LBM, hand grip strength and nPNA in patients
with PEW on peritoneal dialysis.134
Metabolic acidosis is a potential adverse effect of amino
acid-based dialysis solutions.127 However, in agreement with
previous studies,140 we observed that although bicarbonate levels
decreased, levels of bicar-bonate remained within the normal
range.134 To date, only two randomized clinical trials examined the
effects of amino acid-based solutions on clinical outcomes or
nutritional status in patients on peritoneal dialysis.130,133
Of these two studies, only one examined the mortality rate and
showed that patient survival and incidence of peritonitis did not
differ between patients receiv-ing amino acid-based solutions and
those receiv-ing glucose-based solutions over a 3-year follow-up,
although some nutritional parameters such as nPNA and DPI improved
in the former group. The second study only examined changes in
nutritional status.133 Interpretation of published data on the
effects of amino acid-based solutions should therefore be made with
caution because most studies that have demon-strated positive
effects of amino acid-based solutions on outcomes have been small
and observational, and it is therefore uncertain whether an amino
acid-based solution confers a clinical benefit.
Hormonal treatmentsAs patients on dialysis are frequently
hypercatabolic, stimulation of muscle protein anabolism is
therefore an attractive therapeutic option to avoid muscle wasting.
Anabolic hormones that have been tested include growth hormone,
IGF-I and androgenic anabolic ste-roids (Table4). As mentioned
earlier, altered growth hormoneIGF-I axis and growth hormone
resistance are potential mechanisms for PEW in patients on
dialysis; nearly all of the studies that have evaluated the
nutri-tional effects of recombinant human growth hormone (rhGH)
have demonstrated the anabolic effects of decreases in blood urea
nitrogen levels and nPNA.141 These effects have been consistently
observed in patients
Table 1 | Effects of oral supplements on nutritional status in
patients on peritoneal dialysis
Study Study type Population Interventions Followup Results
Shimomura etal. (1993)109
Nonrandomized controlled
36 Supplement of 0.10.3 g protein per kg per day (n = 18);
controls had no supplement (n = 18)
6months serum albumin, prealbumin, transferrin, plasma total
amino acids, and the ratio of essential amino acids to nonessential
amino acids
Heaf etal. (1999)110
No control group 14 Commercial supplement with 40 g protein per
day
10weeks No change in serum albumin, DPI, calorie intake and
nPNA
Eustace etal. (2000)111
Randomized double blind placebo-controlled
47 (18 on PD and 29 on HD)
Oral essential amino acid tablets vs placebo
3months No change in serum albumin level or grip strength;
skinfold thickness
Aguirre Galindo etal. (2003)112
Randomized 100 High protein diet (1.4 g/kg per day) (n = 50) vs
calcium caseinate diet (n = 50)
4months serum albumin level and total protein in both groups
Boudville etal. (2003)113
Single blind crossover 13 on PD Commercial supplement with 475
kcal and 16.6 g protein
ND serum albumin level, total calorie and protein intake
Teixid-Planas etal. (2005)114
Randomized controlled 75 Commercial supplement with 20 g of
protein per day
12months No change in serum albumin level; high rate of
noncompliance and intolerance to commercial protein supplement
Gonzlez-Espinoza etal. (2005)115
Randomized controlled 30 Egg albumin supplement with 30 g
protein per day (n = 13); control (n = 15)
6months serum albumin, total calorie and protein intake, and
nPNA
Poole and Hamad (2008)116
No control group 190 (157 on HD and 33 on PD)
2030 g protein and 500 kcal per day for nondiabetics; 13.8 g
protein and 250 kcal per day for diabetics
3months serum albumin (HD only); no significant improvement in
PD
Moretti etal. (2009)117
Randomized crossover 49 (6 on PD and 43 on HD)
PD: 105 g protein per week; HD: 45 g protein per week
12months No change nPCR and serum albumin level in protein
supplemented group; nPCR and serum albumin level in controls
Abbreviations: DPI, dietary protein intake; HD, hemodialysis;
ND, not determined; nPNA, normalized protein nitrogen appearance;
nPCR, normalized protein catabolic rate; PD, peritoneal
dialysis.
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on peritoneal dialysis.142145 Our work has also shown that rhGH
treatment improves nitrogen balance and increases LBM in
malnourished patients on peritoneal dialysis.143 Another possible
anabolic treatment is IGF-I, which differs from growth hormone in
that it is antilipo-lytic and reduces serum glucose levels.
However, clinical trials using recombinant IGF-I (rIGF-I) are
scarce. Only one pilot study in six patients with PEW on peritoneal
dialysis has shown that rIGF-I treatment resulted in a positive
nitrogen balance.146
Similar to growth hormone and IGF-1, androgenic anabolic
steroids also induce net muscle protein synthe-sis and inhibit
protein catabolic processes.141 Although most studies on androgen
treatment for PEW have been conducted in patients on hemodialysis,
positive effects on nutritional parameters have been reported in
those on peritoneal dialysis.147149 In a double-blind, random-ized
controlled trial, treatment of patients on perito-neal dialysis
with oxymetholone for 6months resulted in a significant increase in
serum albumin levels and
Table 3 | Studies showing neutral effects of 1.1% amino
acid-based solution in patients on peritoneal dialysis
Study Study type Population Interventions Followup (months)
Results
Young etal. (1989)135
Case series 8 One exchange of 1.1% amino acid-based solution
3 No change in serum albumin or prealbumin; no change in serum
bicarbonate; transferrin
Dombros etal. (1990)136
Case series 5 One exchange of 1.1% amino acid-based solution
6 No change in serum albumin, transferrin, DPI, DEI and skinfold
thickness; no change in serum bicarbonate
Dibble etal. (1990)137
Case series 8 One exchange of 1.1% amino acid-based solution
3 No change in total energy intake, MAMC and skinfold
thickness
Maurer et al. (1996)138
Randomized controlled
18 One or two exchanges of a 1.1% amino acid-based solution (n =
9); control (n = 9)
6 No change in serum albumin, transferrin, and LBM; no change in
serum bicarbonate
Grzegorzewska etal. (1999)139
Case series 16 One exchange of 1.1% amino acid-based solution
with antacid (n = 8); control (n = 8)
6 No change in serum albumin, LBM, skinfold thickness, DPI and
DEI; no change in serum bicarbonate
Abbreviations: DEI, dietary energy intake; DPI, dietary protein
intake; LBM, lean body mass; MAMC, mid-arm muscle
circumference.
Table 2 | Studies showing positive effects of 1.1% amino
acid-based solution in patients on peritoneal dialysis
Study Study type Population Interventions Followup Result
Bruno etal. (1989)125
Crossover 6 One exchange of a 1.1% amino acid-based solution
6months nitrogen balance and MAMC; serum bicarbonate
Arfeen etal. (1990)126
Case series 7 Two exchanges of a 1.1% amino acid-based
solution
2months serum albumin; serum bicarbonate
Kopple etal. (1995)127
Case series 19 12 exchanges of a 1.1% amino acid-based
solution
20days nitrogen balance, BUN and transferrin; serum
bicarbonate
Faller etal. (1995)128
Case series 15 One exchange of a 1.1% amino acid-based
solution
3months serum albumin, BUN and transferrin; no change in serum
bicarbonate
Chertow etal. (1995)129
Observational 183 One exchange of a 1.1% amino acid-based
solution
Mean 6.6months serum albumin; no change in serum bicarbonate
Misra etal. (1996)130
Randomized crossover
18 One exchange of a 1.1% amino acid-based solution
6months Improved nutrition score; no change in serum albumin and
transferrin; serum albumin in patients with baseline albumin
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NATURE REVIEWS | NEPHROLOGY VOLUME 8 | MARCH 2012 | 171
LBM.150 However, the long-term efficacy and risk of adverse
effects have not yet been determined in patients with ESRD.
The role of ghrelin as an appetite enhancer is currently being
investigated.151 To date, only two studiesboth of randomized,
double-blind, crossover design and per-formed by the same grouphave
explored the effects of ghrelin in patients on dialysis. A single
subcutane-ous injection of ghrelin resulted in a substantial
increase in energy intake when compared with a placebo in nine
patients with PEW on peritoneal dialysis.152 These find-ings were
subsequently confirmed using daily ghrelin administration for an
extended period of 7days in 12 patients on dialysis.153 Ghrelin
therefore seems to directly target appetite regulation, and is a
potential treatment for patients with PEW on peritoneal
dialysis.
Correction of acidosisA small study of seven patients on
peritoneal dialysis showed a decrease in protein degradation with
correc-tion of acidosis.154 In a randomized, single-blind study,
correction of metabolic acidosis led to increases in body weight
and mid-arm circumference in the first year of
continuous ambulatory peritoneal dialysis.155 Using a similar
protocol, another study also showed that the bene ficial effects of
acidosis correction on nutri-tional status were mediated by the
downregulation of branched-chain amino acid degradation and muscle
proteo lysis via the ubiquitinproteasome system.156 In addition,
another randomized controlled trial showed that treatment with oral
sodium bicarbonate for 12months resulted in increases in SGA score
and nPNA in patients on peritoneal dialysis with acidosis and
Kt/V
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172 | MARCH 2012 | VOLUME 8 www.nature.com/nrneph
ConclusionsImproving the poor nutritional status of patients
with PEW on peritoneal dialysis is difficult owing to the multi
factorial and complicated pathogenesis of this disease. Early
identification is key to rehabilitating these malnourished patients
and avoiding poor outcomes. Thus, a multidisciplinary approach
should be provided through careful nutritional assessment, dietary
counsel-ing and proper nutritional support (Box2). In addition,
management of psychological illnesses and comorbid conditions
should not be ignored. Accurate monitoring and evaluation of
inflammation is of paramount impor-tance given the fact that
inflammation is a key mediator of PEW. However, a paucity of data
are available con-cerning the effect of anti-inflammatory therapies
on nutritional status.
In patients on peritoneal dialysis, factors specific to
peritoneal dialysis should also be considered. In particular,
preservation of RRF should be empha-sized because reduced RRF
adversely affects not only morbidity and mortality but also
nutritional status. Prevention of peritonitis is also important as
recur-rent peritonitis impairs appetite and nutritional status.
Adequate nutritional support should be provided that considers the
inadequate calorie and protein intake in patients on peritoneal
dialysis as well as the substan-tial protein loss into the
dialysate. In this regard, it is tempting to use amino acid-based
dialysis solutions to compensate for protein loss although no data
has con-vincingly shown that these solutions improve patient
survival. Unfortunately, most nutritional intervention trials that
have evaluated the efficacy of oral supple-ments or hormonal
treatments are inconclusive. These studies have not been well
controlled and are limited by short follow-up duration and small
sample sizes. In addition, some crucial safety issues have not been
resolved. Given the paucity of data demonstrating that nutritional
intervention improves clinical outcomes, long-term prospective,
randomized, controlled trials are required to clarify the
beneficial effects of nutri-tional therapies in patients with PEW.
In the meantime, maintenance of good nutritional status and
treatment of PEW with currently available therapies should be an
essential strategy in the management of patients on peritoneal
dialysis.
Box 2 | Management of PEW in peritoneal dialysis
General management Maintain adequate dialysis dose Correct
acidosis Manage comorbid or catabolic conditions Dietary counseling
Encourage adequate food intake:
Daily energy intake 35 kcal/kg of body weight for patients
60yearsProtein intake 1.21.3 g/kg body weight per day* Oral
nutritional supplements
Peritoneal dialysisrelated therapies Preserve residual renal
function Prevent and treat peritonitis Maintain optimal fluid
balance Utilize amino acid-based solutions Use biocompatible
solutions
Potential therapies Appetite stimulants Hormonal treatments
(growth hormone; insulin-like
growth factor I; anabolic steroids; ghrelin) Anti-inflammatory
treatment
*1.0 g/kg body weight per day can be acceptable unless there is
evidence of declining nutritional status. Abbreviation: PEW,
proteinenergy wasting.
Review criteria
The PubMed database was searched for English-language articles
published up to 31st August 2011, with no set earliest date of
publication. The majority were full-text papers. The search terms
used were malnutrition, proteinenergy wasting, peritoneal dialysis,
inflammation, residual renal function, appetite, peritoneal
membrane transport, dialysis dose, inadequate dialysis dietary
intake, dietary counseling, oral supplement, acidosis, amino acid
peritoneal dialysis solution, growth hormone, androgen and
megesterol acetate.
1. Kang, D.H., Kang, E.W., Choi, S.R., Yoon, S.Y. & Han,
D.S. Nutritional problems of Asian peritoneal dialysis patients.
Perit. Dial. Int. 23(Suppl. 2), S58S64 (2003).
2. Cianciaruso, B. etal. Cross-sectional comparison of
malnutrition in continuous ambulatory peritoneal dialysis and
hemodialysis patients. Am. J. Kidney Dis. 26, 475486 (1995).
3. Young, G.A. etal. Nutritional assessment of continuous
ambulatory peritoneal dialysis patients: an international study.
Am. J. Kidney Dis. 17, 462471 (1991).
4. Fouque, D. etal. A proposed nomenclature and diagnostic
criteria for protein-energy wasting in acute and chronic kidney
disease. Kidney Int. 73, 391398 (2008).
5. Dukkipati, R. & Kopple, J.D. Causes and prevention of
protein-energy wasting in chronic kidney failure. Semin. Nephrol.
29, 3949 (2009).
6. Kopple, J.D. Effect of nutrition on morbidity and mortality
in maintenance dialysis patients. Am. J. Kidney Dis. 24, 10021009
(1994).
7. Bergstrom, J. Nutrition and mortality in hemodialysis. J. Am.
Soc. Nephrol. 6, 13291341 (1995).
8. Adequacy of dialysis and nutrition in continuous peritoneal
dialysis: association with clinical outcomes. Canada-USA (CANUSA)
Peritoneal Dialysis Study Group. J. Am. Soc. Nephrol. 7, 198207
(1996).
9. Dong, J., Li, Y., Xu, Y. & Xu, R. Daily protein intake
and survival in patients on peritoneal dialysis. Nephrol. Dial.
Transplant. 26, 37153721 (2011).
10. Bergstrom, J. Why are dialysis patients malnourished? Am. J.
Kidney Dis. 26, 229241 (1995).
11. Wang, A.Y. etal. Independent effects of residual renal
function and dialysis adequacy on actual dietary protein, calorie,
and other nutrient intake
in patients on continuous ambulatory peritoneal dialysis. J. Am.
Soc. Nephrol. 12, 24502457 (2001).
12. Wang, A.Y. & Lai, K.N. The importance of residual renal
function in dialysis patients. Kidney Int. 69, 17261732 (2006).
13. Chung, S.H., Stenvinkel, P., Lindholm, B. & Avesani,
C.M. Identifying and managing malnutrition stemming from different
causes. Perit. Dial. Int. 27 (Suppl. 2), S239S244 (2007).
14. Bossola, M. etal. Malnutrition in hemodialysis patients:
what therapy? Am. J. Kidney Dis. 46, 371386 (2005).
15. Chung, S.H., Carrero, J.J. & Lindholm, B. Causes of poor
appetite in patients on peritoneal dialysis. J. Ren. Nutr. 21, 1215
(2011).
16. Stenvinkel, P., Heimburger, O., Lindholm, B., Kaysen, G.A.
& Bergstrom, J. Are there two types of malnutrition in chronic
renal failure?
REVIEWS
2012 Macmillan Publishers Limited. All rights reserved
-
NATURE REVIEWS | NEPHROLOGY VOLUME 8 | MARCH 2012 | 173
Evidence for relationships between malnutrition, inflammation
and atherosclerosis (MIA syndrome). Nephrol. Dial. Transplant. 15,
953960 (2000).
17. Noh, H. etal. Serum C-reactive protein: a predictor of
mortality in continuous ambulatory peritoneal dialysis patients.
Perit. Dial. Int. 18, 387394 (1998).
18. Stenvinkel, P., Chung, S.H., Heimburger, O. & Lindholm,
B. Malnutrition, inflammation, and atherosclerosis in peritoneal
dialysis patients. Perit. Dial. Int. 21 (Suppl. 3), S157S162
(2001).
19. de Mutsert, R. etal. Excess mortality due to interaction
between protein-energy wasting, inflammation and cardiovascular
disease in chronic dialysis patients. Nephrol. Dial. Transplant.
23, 29572964 (2008).
20. Mitch, W.E., Du, J., Bailey, J.L. & Price, S.R.
Mechanisms causing muscle proteolysis in uremia: the influence of
insulin and cytokines. Miner. Electrolyte Metab. 25, 216219
(1999).
21. Aguilera, A. etal. Anorexigen (TNF-alpha, cholecystokinin)
and orexigen (neuropeptide Y) plasma levels in peritoneal dialysis
(PD) patients: their relationship with nutritional parameters.
Nephrol. Dial. Transplant. 13, 14761483 (1998).
22. Mak, R.H., Cheung, W., Cone, R.D. & Marks,D.L. Leptin
and inflammation-associated cachexia in chronic kidney disease.
Kidney Int. 69, 794797 (2006).
23. Carrero, J.J. etal. Visfatin is increased in chronic kidney
disease patients with poor appetite and correlates negatively with
fasting serum amino acids and triglyceride levels. Nephrol. Dial.
Transplant. 25, 901906 (2010).
24. Price, S.R. etal. Muscle wasting in insulinopenic rats
results from activation of the ATP-dependent, ubiquitin-proteasome
proteolytic pathway by a mechanism including gene transcription. J.
Clin. Invest. 98, 17031708 (1996).
25. Wellen, K.E. & Hotamisligil, G.S. Inflammation, stress,
and diabetes. J. Clin. Invest. 115, 11111119 (2005).
26. Lee, S.W., Park, G.H., Song, J.H., Hong, K.C. & Kim,
M.J. Insulin resistance and muscle wasting in non-diabetic
end-stage renal disease patients. Nephrol. Dial. Transplant. 22,
25542562 (2007).
27. Bayraktar, G. etal. Oral health and inflammation in patients
with end-stage renal failure. Perit. Dial. Int. 29, 472479
(2009).
28. Cheng, L.T., Tang, W. & Wang, T. Strong association
between volume status and nutritional status in peritoneal dialysis
patients. Am. J. Kidney Dis. 45, 891902 (2005).
29. Lai, K.N. & Leung, J.C. Inflammation in peritoneal
dialysis. Nephron Clin. Pract. 116, c11c18 (2010).
30. Clinical practice guidelines for nutrition in chronic renal
failure. K/DOQI, National Kidney Foundation. Am. J. Kidney Dis. 35
(Suppl. 2), S1140 (2000).
31. Wang, A.Y. etal. Nutrient intake during peritoneal dialysis
at the Prince of Wales Hospital in Hong Kong. Am. J. Kidney Dis.
49, 682692 (2007).
32. Lindholm, B., Wang, T., Heimburger, O. & Bergstrom, J.
Influence of different treatments and schedules on the factors
conditioning the nutritional status in dialysis patients. Nephrol.
Dial. Transplant. 13 (Suppl. 6), 6673 (1998).
33. Bazanelli, A.P. etal. Resting energy expenditure in
peritoneal dialysis patients. Perit. Dial. Int. 26, 697704
(2006).
34. Bergstrom, J., Furst, P., Alvestrand, A. & Lindholm, B.
Protein and energy intake, nitrogen balance and nitrogen losses in
patients treated with continuous ambulatory peritoneal dialysis.
Kidney Int. 44, 10481057 (1993).
35. Carrero, J.J. etal. Appetite disorders in uremia. J. Ren.
Nutr. 18, 107113 (2008).
36. Aguilera, A. etal. Gastrointestinal and pancreatic function
in peritoneal dialysis patients: their relationship with
malnutrition and peritoneal membrane abnormalities. Am. J. Kidney
Dis. 42, 787796 (2003).
37. Kalantar-Zadeh, K., Ikizler, T.A., Block, G., Avram,M.M.
& Kopple, J.D. Malnutrition-inflammation complex syndrome in
dialysis patients: causes and consequences. Am. J. Kidney Dis. 42,
864881 (2003).
38. Zheng, Z.H. etal. Acute effects of peritoneal dialysis
solutions on appetite in non-uremic rats. Kidney Int. 60, 23922398
(2001).
39. Stompor, T. etal. Association between gastric emptying rate
and nutritional status in patients treated with continuous
ambulatory peritoneal dialysis. Perit. Dial. Int. 22, 500505
(2002).
40. Van, V. etal. Influence of dialysate on gastric emptying
time in peritoneal dialysis patients. Perit. Dial. Int. 22, 3238
(2002).
41. Cummings, D.E. etal. A preprandial rise in plasma ghrelin
levels suggests a role in meal initiation in humans. Diabetes 50,
17141719 (2001).
42. Perez-Fontan, M. etal. Plasma ghrelin levels in patients
undergoing haemodialysis and peritoneal dialysis. Nephrol. Dial.
Transplant. 19, 20952100 (2004).
43. Aguilera, A. etal. Ghrelin plasma levels and appetite in
peritoneal dialysis patients. Adv. Perit. Dial. 20, 194199
(2004).
44. Perez-Fontan, M. etal. Acute plasma ghrelin and leptin
responses to oral feeding or intraperitoneal hypertonic
glucose-based dialysate in patients with chronic renal failure.
Kidney Int. 68, 28772885 (2005).
45. Zheng, Z.H. etal. Bicarbonate-based peritoneal dialysis
solution has less effect on ingestive behavior than lactate-based
peritoneal dialysis solution. Perit. Dial. Int. 29, 656663
(2009).
46. Blumenkrantz, M.J. etal. Protein losses during peritoneal
dialysis. Kidney Int. 19, 593602 (1981).
47. Kathuria, P. etal. Effect of dialysis modality and membrane
transport characteristics on dialysate protein losses of patients
on peritoneal dialysis. Perit. Dial. Int. 17, 449454 (1997).
48. Kang, D.H. etal. Relationship of peritoneal membrane
transport characteristics to the nutritional status in CAPD
patients. Nephrol. Dial. Transplant. 14, 17151722 (1999).
49. Pecoits-Filho, R. etal. Plasma and dialysate IL-6 and VEGF
concentrations are associated with high peritoneal solute transport
rate. Nephrol. Dial. Transplant. 17, 14801486 (2002).
50. Churchill, D.N. etal. Increased peritoneal membrane
transport is associated with decreased patient and technique
survival for continuous peritoneal dialysis patients. The
Canada-USA (CANUSA) Peritoneal Dialysis Study Group. J. Am. Soc.
Nephrol. 9, 12851292 (1998).
51. Rumpsfeld, M., McDonald, S.P. & Johnson, D.W. Higher
peritoneal transport status is associated with higher mortality and
technique failure in the Australian and New Zealand peritoneal
dialysis patient populations. J. Am. Soc. Nephrol. 17, 271278
(2006).
52. Cueto-Manzano, A.M., Espinosa, A., Hernandez,A. &
Correa-Rotter, R. Peritoneal transport kinetics correlate with
serum albumin
but not with the overall nutritional status in CAPD patients.
Am. J. Kidney Dis. 30, 229236 (1997).
53. Szeto, C.C., Law, M.C., Wong, T.Y., Leung, C.B. & Li,
P.K. Peritoneal transport status correlates with morbidity but not
longitudinal change of nutritional status of continuous ambulatory
peritoneal dialysis patients: a 2-year prospective study. Am. J.
Kidney Dis. 37, 329336 (2001).
54. Brimble, K.S., Walker, M., Margetts, P.J., Kundhal, K.K.
& Rabbat, C.G. Meta-analysis: peritoneal membrane transport,
mortality, and technique failure in peritoneal dialysis. J. Am.
Soc. Nephrol. 17, 25912598 (2006).
55. Johnson, D.W. etal. Superior survival of high transporters
treated with automated versus continuous ambulatory peritoneal
dialysis. Nephrol. Dial. Transplant. 25, 19731979 (2010).
56. Chung, S.H., Heimburger, O. & Lindholm, B. Poor outcomes
for fast transporters on PD: the rise and fall of a clinical
concern. Semin. Dial. 21, 710 (2008).
57. Shemin, D., Bostom, A.G., Laliberty, P. & Dworkin, L.D.
Residual renal function and mortality risk in hemodialysis
patients. Am. J. Kidney Dis. 38, 8590 (2001).
58. Wang, A.Y. etal. Resting energy expenditure and subsequent
mortality risk in peritoneal dialysis patients. J. Am. Soc.
Nephrol. 15, 31343143 (2004).
59. Szeto, C.C. etal. Independent effects of residual renal
function and dialysis adequacy on nutritional status and patient
outcome in continuous ambulatory peritoneal dialysis. Am. J. Kidney
Dis. 34, 10561064 (1999).
60. Suda, T. etal. The contribution of residual renal function
to overall nutritional status in chronic haemodialysis patients.
Nephrol. Dial. Transplant. 15, 396401 (2000).
61. Wang, A.Y. etal. Evaluation of handgrip strength as a
nutritional marker and prognostic indicator in peritoneal dialysis
patients. Am. J. Clin. Nutr. 81, 7986 (2005).
62. Pecoits-Filho, R. etal. Associations between circulating
inflammatory markers and residual renal function in CRF patients.
Am. J. Kidney Dis. 41, 12121218 (2003).
63. Bammens, B., Evenepoel, P., Verbeke, K. & Vanrenterghem,
Y. Time profiles of peritoneal and renal clearances of different
uremic solutes in incident peritoneal dialysis patients. Am. J.
Kidney Dis. 46, 512519 (2005).
64. Marcus, R.G., Cohl, E. & Uribarri, J. Middle molecule
clearance does not influence protein intake in hemodialysis
patients. Am. J. Kidney Dis. 31, 491494 (1998).
65. Bailey, J.L. etal. The acidosis of chronic renal failure
activates muscle proteolysis in rats by augmenting transcription of
genes encoding proteins of the ATP-dependent ubiquitin-proteasome
pathway. J. Clin. Invest. 97, 14471453 (1996).
66. Ballmer, P.E. etal. Chronic metabolic acidosis decreases
albumin synthesis and induces negative nitrogen balance in humans.
J. Clin. Invest. 95, 3945 (1995).
67. Brungger, M., Hulter, H.N. & Krapf, R. Effect of chronic
metabolic acidosis on the growth hormone/IGF-1 endocrine axis: new
cause of growth hormone insensitivity in humans. Kidney Int. 51,
216221 (1997).
68. Chiu, Y.W., Kopple, J.D. & Mehrotra, R. Correction of
metabolic acidosis to ameliorate wasting in chronic kidney disease:
goals and strategies. Semin. Nephrol. 29, 6774 (2009).
69. Kang, S.W. etal. Impact of metabolic acidosis on serum
albumin and other nutritional
REVIEWS
2012 Macmillan Publishers Limited. All rights reserved
-
174 | MARCH 2012 | VOLUME 8 www.nature.com/nrneph
parameters in long-term CAPD patients. Adv. Perit. Dial. 13,
249252 (1997).
70. Kang, D.H. etal. Metabolic acidosis and composite
nutritional index (CNI) in CAPD patients. Clin. Nephrol. 53, 124131
(2000).
71. Blake, P.G. Growth hormone and malnutrition in dialysis
patients. Perit. Dial. Int. 15, 210216 (1995).
72. Fryburg, D.A., Gelfand, R.A. & Barrett, E.J. Growth
hormone acutely stimulates forearm muscle protein synthesis in
normal humans. Am. J. Physiol. 260, E499E504 (1991).
73. Spiegel, D.M. & Breyer, J.A. Serum albumin: a predictor
of long-term outcome in peritoneal dialysis patients. Am. J. Kidney
Dis. 23, 283285 (1994).
74. Han, S.H. etal. Improving outcome of CAPD: twenty-five years
experience in a single Korean center. Perit. Dial. Int. 27, 432440
(2007).
75. Han, D.S. etal. Factors affecting low values of serum
albumin in CAPD patients. Adv. Perit. Dial. 12, 288292 (1996).
76. Goldwasser, P., Feldman, J.G. & Barth, R.H. Serum
prealbumin is higher in peritoneal dialysis than in hemodialysis: a
meta-analysis. Kidney Int. 62, 276281 (2002).
77. Kalantar-Zadeh, K. & Kopple, J.D. Obesity paradox in
patients on maintenance dialysis. Contrib. Nephrol. 151, 5769
(2006).
78. Snyder, J.J., Foley, R.N., Gilbertson, D.T., Vonesh,E.F.
& Collins, A.J. Body size and outcomes on peritoneal dialysis
in the United States. Kidney Int. 64, 18381844 (2003).
79. Stack, A.G., Murthy, B.V. & Molony, D.A. Survival
differences between peritoneal dialysis and hemodialysis among
large ESRD patients in the United States. Kidney Int. 65, 23982408
(2004).
80. Enia, G. etal. Long-term CAPD patients are volume expanded
and display more severe left ventricular hypertrophy than
haemodialysis patients. Nephrol. Dial. Transplant. 16, 14591464
(2001).
81. Abbott, K.C. etal. Body mass index and peritoneal dialysis:
exceptions to the exception in reverse epidemiology? Semin. Dial.
20, 561565 (2007).
82. McDonald, S.P., Collins, J.F. & Johnson, D.W. Obesity is
associated with worse peritoneal dialysis outcomes in the Australia
and New Zealand patient populations. J. Am. Soc. Nephrol. 14,
28942901 (2003).
83. Honda, H. etal. Obese sarcopenia in patients with end-stage
renal disease is associated with inflammation and increased
mortality. Am. J. Clin. Nutr. 86, 633638 (2007).
84. Ramkumar, N., Pappas, L.M. & Beddhu, S. Effect of body
size and body composition on survival in peritoneal dialysis
patients. Perit. Dial. Int. 25, 461469 (2005).
85. Bargman, J.M. The rationale and ultimate limitations of urea
kinetic modelling in the estimation of nutritional status. Perit.
Dial. Int. 16, 347351 (1996).
86. Bazanelli, A.P., Kamimura, M.A., Vasselai, P., Draibe, S.A.
& Cuppari, L. Underreporting of energy intake in peritoneal
dialysis patients. J.Ren. Nutr. 20, 263269 (2010).
87. Bergstrom, J. Mechanisms of uremic suppression of appetite.
J. Ren. Nutr. 9, 129132 (1999).
88. Fung, L. etal. Dialysis adequacy and nutrition determine
prognosis in continuous ambulatory peritoneal dialysis patients. J.
Am. Soc. Nephrol. 7, 737744 (1996).
89. Williams, P., Jones, J. & Marriott, J. Do increases in
dialysis dose in CAPD patients lead to nutritional improvements?
Nephrol. Dial. Transplant. 9, 18411842 (1994).
90. Lynn, R.I., Fishbane, S. & Ginsberg, N.S. The effect of
KT/V(urea) on nitrogen appearance and appetite in peritoneal
dialysis. Perit. Dial. Int. 15(Suppl. 5), S50S52 (1995).
91. Malhotra, D. etal. Serum albumin in continuous peritoneal
dialysis: its predictors and relationship to urea clearance. Kidney
Int. 50, 243249 (1996).
92. Harty, J., Boulton, H., Faragher, B., Venning, M. &
Gokal, R. The influence of small solute clearance on dietary
protein intake in continuous ambulatory peritoneal dialysis
patients: a methodologic analysis based on cross-sectional and
prospective studies. Am. J. Kidney Dis. 28, 553560 (1996).
93. Davies, S.J., Phillips, L., Griffiths, A.M., Naish,P.F.
& Russell, G.I. Analysis of the effects of increasing delivered
dialysis treatment to malnourished peritoneal dialysis patients.
Kidney Int. 57, 17431754 (2000).
94. Paniagua, R. etal. Effects of increased peritoneal
clearances on mortality rates in peritoneal dialysis: ADEMEX, a
prospective, randomized, controlled trial. J. Am. Soc. Nephrol. 13,
13071320 (2002).
95. Lo, W.K. etal. Effect of Kt/V on survival and clinical
outcome in CAPD patients in a randomized prospective study. Kidney
Int. 64, 649656 (2003).
96. Mak, S.K. etal. Randomized prospective study of the effect
of increased dialytic dose on nutritional and clinical outcome in
continuous ambulatory peritoneal dialysis patients. Am. J. Kidney
Dis. 36, 105114 (2000).
97. Nolph, K.D. etal. A new approach to optimizing urea
clearances in hemodialysis and continuous ambulatory peritoneal
dialysis. ASAIO J. 41, M446M451 (1995).
98. Ronco, C. Adequacy of peritoneal dialysis is more than Kt/V.
Nephrol. Dial. Transplant. 12 (Suppl. 1), 6873 (1997).
99. Oreopoulos, D.G. The optimization of continuous ambulatory
peritoneal dialysis. Kidney Int. 55, 11311149 (1999).
100. Kawanishi, H., Moriishi, M. & Tsuchiya, S. Evaluation
of dialysis dose during combination therapy with peritoneal
dialysis and hemodialysis. Adv. Perit. Dial. 23, 135139 (2007).
101. Bargman, J.M., Thorpe, K.E. & Churchill, D.N. Relative
contribution of residual renal function and peritoneal clearance to
adequacy of dialysis: a reanalysis of the CANUSA study. J. Am. Soc.
Nephrol. 12, 21582162 (2001).
102. Wang, A.Y. etal. Important factors other than dialysis
adequacy associated with inadequate dietary protein and energy
intakes in patients receiving maintenance peritoneal dialysis. Am.
J. Clin. Nutr. 77, 834841 (2003).
103. Prasad, N. etal. Changes in nutritional status on follow-up
of an incident cohort of continuous ambulatory peritoneal dialysis
patients. J. Ren. Nutr. 18, 195201 (2008).
104. Martin-Del-Campo, F. etal. Conventional nutritional
counselling maintains nutritional status of patients on continuous
ambulatory peritoneal dialysis in spite of systemic inflammation
and decrease of residual renal function. Nephrology (Carlton) 14,
493498 (2009).
105. Sutton, D., Higgins, B. & Stevens, J.M. Continuous
ambulatory peritoneal dialysis patients are unable to increase
dietary intake to recommended levels. J. Ren. Nutr. 17, 329335
(2007).
106. Dombros, N. etal. European best practice guidelines for
peritoneal dialysis. 8 Nutrition in peritoneal dialysis. Nephrol.
Dial. Transplant. 20(Suppl. 9), ix28ix33 (2005).
107. Blumenkrantz, M.J., Kopple, J.D., Moran, J.K. & Coburn,
J.W. Metabolic balance studies and dietary protein requirements in
patients undergoing continuous ambulatory peritoneal dialysis.
Kidney Int. 21, 849861 (1982).
108. Fouque, D., Pelletier, S., Mafra, D. & Chauveau, P.
Nutrition and chronic kidney disease. Kidney Int. 80, 348357
(2011).
109. Shimomura, A., Tahara, D. & Azekura, H. Nutritional
improvement in elderly CAPD patients with additional high protein
foods. Adv. Perit. Dial. 9, 8086 (1993).
110. Heaf, J.G., Honore, K., Valeur, D. & Randlov, A. The
effect of oral protein supplements on the nutritional status of
malnourished CAPD patients. Perit. Dial. Int. 19, 7881 (1999).
111. Eustace, J.A. etal. Randomized double-blind trial of oral
essential amino acids for dialysis-associated hypoalbuminemia.
Kidney Int. 57, 25272538 (2000).
112. Aguirre Galindo, B.A. etal. Effect of polymeric diets in
patients on continuous ambulatory peritoneal dialysis. Perit. Dial.
Int. 23, 434439 (2003).
113. Boudville, N., Rangan, A. & Moody, H. Oral nutritional
supplementation increases caloric and protein intake in peritoneal
dialysis patients. Am. J. Kidney Dis. 41, 658663 (2003).
114. Teixido-Planas, J. etal. Oral protein-energy supplements in
peritoneal dialysis: a multicenter study. Perit. Dial. Int. 25,
163172 (2005).
115. Gonzalez-Espinoza, L. etal. Randomized, open label,
controlled clinical trial of oral administration of an egg
albumin-based protein supplement to patients on continuous
ambulatory peritoneal dialysis. Perit. Dial. Int. 25, 173180
(2005).
116. Poole, R. & Hamad, A. Nutrition supplements in dialysis
patients: use in peritoneal dialysis patients and diabetic
patients. Adv. Perit. Dial. 24, 118124 (2008).
117. Moretti, H.D., Johnson, A.M. & Keeling-Hathaway, T.J.
Effects of protein supplementation in chronic hemodialysis and
peritoneal dialysis patients. J. Ren. Nutr. 19, 298303 (2009).
118. Inui, A. Cancer anorexia-cachexia syndrome: current issues
in research and management. CA Cancer J. Clin. 52, 7291 (2002).
119. Lien, Y.H. & Ruffenach, S.J. Low dose megestrol
increases serum albumin in malnourished dialysis patients. Int. J.
Artif. Organs 19, 147150 (1996).
120. Costero, O. etal. Treatment of anorexia and malnutrition in
peritoneal dialysis patients with megestrol acetate. Adv. Perit.
Dial. 20, 209212 (2004).
121. Golebiewska, J. etal. Influence of megestrol acetate on
nutrition and inflammation in dialysis patients - preliminary
results. Acta Biochim. Pol. 56, 733737 (2009).
122. Boccanfuso, J.A., Hutton, M. & McAllister, B. The
effects of megestrol acetate on nutritional parameters in a
dialysis population. J. Ren. Nutr. 10, 3643 (2000).
123. Park, M.S. etal. Peritoneal transport during dialysis with
amino acid-based solutions. Perit. Dial. Int. 13, 280288
(1993).
124. Garibotto, G. etal. Acute effects of peritoneal dialysis
with dialysates containing dextrose or dextrose and amino acids on
muscle protein turnover in patients with chronic renal failure.
J.Am. Soc. Nephrol. 12, 557567 (2001).
125. Bruno, M. etal. CAPD with an amino acid dialysis solution:
a long-term, cross-over study. Kidney Int. 35, 11891194 (1989).
126. Arfeen, S., Goodship, T.H., Kirkwood, A. & Ward,M.K.
The nutritional/metabolic and
REVIEWS
2012 Macmillan Publishers Limited. All rights reserved
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NATURE REVIEWS | NEPHROLOGY VOLUME 8 | MARCH 2012 | 175
hormonal effects of 8weeks of continuous ambulatory peritoneal
dialysis with a 1% amino acid solution. Clin. Nephrol. 33, 192199
(1990).
127. Kopple, J.D. etal. Treatment of malnourished CAPD patients
with an amino acid based dialysate. Kidney Int. 47, 11481157
(1995).
128. Faller, B. etal. Clinical evaluation of an optimized 1.1%
amino-acid solution for peritoneal dialysis. Nephrol. Dial.
Transplant. 10, 14321437 (1995).
129. Chertow, G.M. etal. Laboratory surrogates of nutritional
status after administration of intraperitoneal amino acid-based
solutions in ambulatory peritoneal dialysis patients. J. Ren. Nutr.
3, 116123 (1995).
130. Misra, M., Ashworth, J., Reaveley, D.A., Muller,B. &
Brown, E.A. Nutritional effects of amino acid dialysate (Nutrineal)
in CAPD patients. Adv. Perit. Dial. 12, 311314 (1996).
131. Jones, M. etal. Treatment of malnutrition with 1.1% amino
acid peritoneal dialysis solution: results of a multicenter
outpatient study. Am. J. Kidney Dis. 32, 761769 (1998).
132. Taylor, G.S., Patel, V., Spencer, S., Fluck, R.J. &
McIntyre, C.W. Long-term use of 1.1% amino acid dialysis solution
in hypoalbuminemic continuous ambulatory peritoneal dialysis
patients. Clin. Nephrol. 58, 445450 (2002).
133. Li, F.K. etal. A 3-year, prospective, randomized,
controlled study on amino acid dialysate in patients on CAPD. Am.
J. Kidney Dis. 42, 173183 (2003).
134. Park, M.S. etal. New insight of amino acid-based dialysis
solutions. Kidney Int. Suppl. 103, S110S114 (2006).
135. Young, G.A. etal. The use of an amino-acid-based CAPD fluid
over 12weeks. Nephrol. Dial. Transplant. 4, 285292 (1989).
136. Dombros, N.V. etal. Six-month overnight intraperitoneal
amino-acid infusion in continuous ambulatory peritoneal dialysis
(CAPD) patientsno effect on nutritional status. Perit. Dial. Int.
10, 7984 (1990).
137. Dibble, J.B., Young, G.A., Hobson, S.M. & Brownjohn,
A.M. Amino-acid-based continuous ambulatory peritoneal dialysis
(CAPD) fluid over twelve weeks: effects on carbohydrate and lipid
metabolism. Perit. Dial. Int. 10, 7177 (1990).
138. Maurer, O. etal. Six-month overnight administration of
intraperitoneal amino acids does not improve lean mass. Clin.
Nephrol. 45, 303309 (1996).
139. Grzegorzewska, A.E., Mariak, I., Dobrowolska-Zachwieja, A.
& Szajdak, L. Effects of amino acid dialysis solution on the
nutrition of continuous ambulatory peritoneal dialysis patients.
Perit. Dial. Int. 19, 462470 (1999).
140. Tjiong, H.L. etal. Dialysate as food: combined amino acid
and glucose dialysate improves protein anabolism in renal failure
patients on automated peritoneal dialysis. J. Am. Soc. Nephrol. 16,
14861493 (2005).
141. Fouque, D., Guebre-Egziabher, F. & Laville, M. Advances
in anabolic interventions for malnourished dialysis patients. J.
Ren. Nutr. 13, 161165 (2003).
142. Ikizler, T.A. etal. Short-term effects of recombinant human
growth hormone in CAPD patients. Kidney Int. 46, 11781183
(1994).
143. Kang, D.H. etal. Recombinant human growth hormone improved
nutritional status of undernourished adult CAPD patients. J. Am.
Soc. Nephrol. 5, 494 (1994).
144. Ikizler, T.A. etal. Effects of recombinant human growth
hormone on plasma and dialysate amino acid profiles in CAPD
patients. Kidney Int. 50, 229234 (1996).
145. Iglesias, P. etal. Recombinant human growth hormone therapy
in malnourished dialysis patients: a randomized controlled study.
Am. J. Kidney Dis. 32, 454463 (1998).
146. Fouque, D., Peng, S.C., Shamir, E. & Kopple,J.D.
Recombinant human insulin-like growth factor-1 induces an anabolic
response in malnourished CAPD patients. Kidney Int. 57, 646654
(2000).
147. Dombros, N.V., Digenis, G.E., Soliman, G. & Oreopoulos,
D.G. Anabolic steroids in the treatment of malnourished CAPD
patients: a retrospective study. Perit. Dial. Int. 14, 344347
(1994).
148. Johansen, K.L., Mulligan, K. & Schambelan, M. Anabolic
effects of nandrolone decanoate in patients receiving dialysis: a
randomized controlled trial. JAMA 281, 12751281 (1999).
149. Navarro, J.F., Mora, C., Macia, M. & Garcia, J.
Randomized prospective comparison between
erythropoietin and androgens in CAPD patients. Kidney Int. 61,
15371544 (2002).
150. Aramwit, P., Palapinyo, S., Wiwatniwong, S. &
Supasyndh, O. The efficacy of oxymetholone in combination with
erythropoietin on hematologic parameters and muscle mass in CAPD
patients. Int. J. Clin. Pharmacol. Ther. 48, 803813 (2010).
151. Wren, A.M. etal. Ghrelin enhances appetite and increases
food intake in humans. J. Clin. Endocrinol. Metab. 86, 5992
(2001).
152. Wynne, K. etal. Subcutaneous ghrelin enhances acute food
intake in malnourished patients who receive maintenance peritoneal
dialysis: a randomized, placebo-controlled trial. J. Am. Soc.
Nephrol. 16, 21112118 (2005).
153. Ashby, D.R. etal. Sustained appetite improvement in
malnourished dialysis patients by daily ghrelin treatment. Kidney
Int. 76, 199206 (2009).
154. Graham, K.A. etal. Correction of acidosis in CAPD decreases
whole body protein degradation. Kidney Int. 49, 13961400
(1996).
155. Stein, A. etal. Role of an improvement in acid-base status
and nutrition in CAPD patients. Kidney Int. 52, 10891095
(1997).
156. Pickering, W.P. etal. Nutrition in CAPD: serum bicarbonate
and the ubiquitin-proteasome system in muscle. Kidney Int. 61,
12861292 (2002).
157. Szeto, C.C., Wong, T.Y., Chow, K.M., Leung,C.B. & Li,
P.K. Oral sodium bicarbonate for the treatment of metabolic
acidosis in peritoneal dialysis patients: a randomized
placebo-control trial. J. Am. Soc. Nephrol. 14, 21192126
(2003).
158. Montenegro, J. etal. Long-term clinical experience with
pure bicarbonate peritoneal dialysis solutions. Perit. Dial. Int.
26, 8994 (2006).
159. Mehrotra, R. etal. Effect of high-normal compared with
low-normal arterial pH on protein balances in automated peritoneal
dialysis patients. Am. J. Clin. Nutr. 90, 15321540 (2009).
Author contributionsAll authors contributed equally to all
aspects of the article.
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Nutrition in patients on peritoneal dialysisSeung-Hyeok Han and
Dae-Suk HanIntroduction Nomenclature Key pointsCauses and
pathogenesis of PEW Figure 1 | The causes of proteinenergy wasting
in patients on peritoneal dialysis.Box 1 | ISRNM criteria for
diagnosis of PEW in patients with ESRDAssessment of nutritional
status Prevention and treatment of PEW Box 2 | Management of PEW in
peritoneal dialysis Review criteriaConclusionsAuthor
contributions