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Nutrition in patients on peritoneal dialysis

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DOI: 10.1038/nrneph.2012.12 · Source: PubMed

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 REVIEWS
Nutrition in patients on peritoneal dialysis
Seung-Hyeok Han and Dae-Suk Han
Abstract | Protein–energy 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 20 years, 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, 163–175 (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 protein–energy 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.1–5 Accumulating evidence indicates that
PEW is an important predictor of morbidity and mortal-
ity in patients on dialysis and impairs quality of life. 6–9
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
Competing interests
The authors declare no competing interests.
conditions.11–14 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 ‘type 1 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, protein–
energy malnutrition, malnutrition–­i nflammation
athero­s clerosis (MIA) syndrome and malnutrition–
inflammation 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 Division of Nephrology,
orders including resistance to insulin, growth hormone, Department of Internal
Medicine, Yonsei
and insulin-like growth factor (IGF)‑I can cause loss of University College of
muscle mass despite adequate nutrient intake.5,13 As the Medicine, 50 Yonsei-ro
altered nutritional status associated with these condi- Seodaemun-gu, Seoul
120-752, Korea
tions is not solely attributed to reduced nutrient intake, (S.‑H. Han, D.‑S. Han).
it cannot be corrected merely by increasing intake.
Correspondence to:
To avoid confusion, the term PEW was proposed by a D.‑S. Han
panel of experts from the International Society of Renal dshan@yuhs.ac

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© 2012 Macmillan Publishers Limited. All rights reserved
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Key points
■■ Protein–energy 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
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
character­ized 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,
psycho­logical 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
morbid­ity and mortality. Moreover, elevated levels of
C‑reactive protein (a serum inflammatory marker)
predicts mortal­ity 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
mortal­ity 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
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© 2012 Macmillan Publishers Limited. All rights reserved
increasing protein hydrolysis and muscle-protein break-
down through activation of the ubiquitin–proteasome
proteolytic pathway or nuclear factor κB 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 leptin—a 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;27–29
of note, these factors (unlike those discussed above) are
potentially reversible. In fact, when the fluid 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
<60 years and 30–35 kcal/kg for patients >60 years and
daily protein intake of 1.2–1.3 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 energy 33 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
(Figure 1).35–37 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

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 per se 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 9–12 g
of total protein and 6–8 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
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© 2012 Macmillan Publishers Limited. All rights reserved
REVIEWS
Factors related to uremia Factors related to peritoneal dialysis
Inflammation Loss of nutrients
into dialysate
Inadequate dialysis
Loss of residual
renal function
Anorexia
Appetite loss due to
glucose absorption
Inadequate Protein–energy
nutrient intake wasting
from dialysate
Abdominal discomfort
Hypercatabolism induced by dialysate
Chronic acidosis Peritonitis
Comorbid conditions: Bioincompatible
diabetes mellitus, solution?
cardiovascular disease,
infection
Figure 1 | The causes of protein–energy wasting in patients on peritoneal dialysis.
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 20 years, 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.11,59–61 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
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Box 1 | ISRNM criteria for diagnosis of PEW in patients with ESRD
A diagnosis of PEW requires that at least three out of the four listed categories
should be met and at least one test in each of the selected category should be
included.
Serum chemistry
■■ Serum albumin level (measured using the bromocresol green method) <38 g/l
■■ Serum prealbumin level (transthyretin) <30 mg/dl
■■ Serum cholesterol level <2.59 mmol/l (not valid if low concentrations are
caused by abnormally high urinary or gastrointestinal protein losses, liver
disease or cholesterol-lowering medicines)
Body mass
■■ BMI <22 kg/m2 ≤65 years, <23 kg/m2 >65 years (a lower BMI might be
desirable for certain Asian populations; weight must be edema-free mass)
■■ Unintentional weight loss over time: ≥5% over 3 months or ≥10% over 6 months
■■ Total body fat percentage <10%
Muscle mass
■■ Muscle wasting: reduced muscle mass ≥5% over 3 months or ≥10% over
6 months
■■ Reduced MAMC area as measured by a trained anthropometrist (reduction
>10% in relation to the 50th percentile of the reference population)
■■ Creatinine appearance (of note, appearance is influenced by muscle mass and
meat intake)
Dietary intake
■■ Unintentionally low DPI <0.80 g/kg per day for at least 2 months (which
can be assessed by dietary diaries and interviews, or for protein intake by
calculation of the normalized protein equivalent of total nitrogen appearance
[normalized protein nitrogen appearance or normalized protein catabolic rate]
as determined by urea kinetic measurements
■■ Unintentional low DEI <25 kcal/kg per day for at least 2 months
Abbreviations: DEI, dietary energy intake; DPI, dietary protein intake; ESRD, end-stage renal
disease; ISRNM, International Society of Renal Nutrition and Metabolism; MAMC, mid-arm
muscle circumference; PEW, protein–energy wasting.
Hypercatabolic state
Patients 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 18–20 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 <18 mmol/l) had low serum albumin levels and
high composite nutritional index scores. These findings
suggest that acidosis has a protein catabolic effect, which
leads to poor nutrition in severely acidotic patients.70
Why mild to moderate metabolic acidosis was associ-
ated with favorable nutritional status is unclear, but high
protein intake in well-dialyzed patients can partly explain
this finding. Of note, however, this cross-sectional study
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© 2012 Macmillan Publishers Limited. All rights reserved
does not prove causality. The therapeutic target of bicar-
bonate levels ≥22 mmol/l as suggested by the K‑DOQI
guideline seems to be reasonable, given the considerable
concern about protein degradation and muscle wasting
in patients with persistent acidosis.30
PEW resulting from resistance to growth hormone and
IGF‑I occurs in patients who have an abnormal growth
hormone–IGF axis despite normal or high levels of
endogenous growth hormone and IGF‑I.71 Furthermore,
high levels of IGF-binding proteins in these patients
reduces the amount of free IGF‑I.71 As growth hormone
exerts an anabolic effect and thereby induces protein
preservation and de novo protein synthesis,72 the abnor-
mal growth hormone–IGF axis in uremia shifts the meta-
bolic balance from anabolism to catabolism. By contrast,
increased serum levels of catabolic hormones (such as
glucagon and parathyroid hormone) and deficiency in
1,25-dihydroxycholecalciferol might also promote the
development of PEW.5
Assessment of nutritional status
A wide variety of clinical and biochemical methods are
available to detect PEW in patients with ESRD. BMI,
SGA score, anthropometric measurements, biochemi-
cal parameters (such as serum albumin level) and DPI
have traditionally been used in clinical practice; however,
no single method is precisely indicative of PEW. Many
investigators therefore cautiously interpret data combined
from several parameters rather than from a single test.
The ISRNM panel have proposed comprehensive diag-
nostic criteria for PEW in patients with CKD (Box 1).4
The criteria consist of four main categories (serum chem-
istry, body mass, muscle mass and dietary intake) that
encompass both clinical and biochemical features of PEW.
A clinical diagnosis of PEW according to the ISRNM
guidelines requires that at least three out of the four listed
categories (and at least one test in each of the selected
categories) are satisfied. The panel also recommended
helpful additional measures of nutrition and inflamma-
tion, which include assessment of appetite, food intake
and energy expenditure; body mass and composition;
laboratory markers; and nutritional scoring systems.
Although each test in the four main categories can
be readily used to test for PEW in patients on dialy-
sis, several considerations should be made when these
criteria are applied to those on peritoneal dialysis.
Serum chemistry
Among various biochemical parameters, low serum
albumin concentration is a strong predictor of mortal­
ity in patients on peritoneal dialysis. 73 Indeed, our
25 years’ experience with peritoneal dialysis has shown
that decreased serum albumin levels are independently
associated with mortality.74 However, as serum albumin
has a long half-life of approximately 20 days and can
be affected by inflammation, losses into dialysate and
fluid status, levels of serum albumin should be inter-
preted with caution when diagnosing PEW. 13,28,75 By
contrast, prealbumin has a relatively short half-life (of
approximately 2 days), and so is considered to be a more

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 hemodialysis—possibly 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 hemo­dialysis
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 considera­tion
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
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REVIEWS
The ISRNM panel recommended other potential tools
for assessment of PEW that include scoring systems
such as the SGA score and malnutrition–inflammation
score—both 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,89–93 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 Kong 95 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 12 months 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 1.8.97–99 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,
REVIEWS
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 5–6 days per week
of peritoneal dialysis regimen in patients affected by
underdialysis or fluid overload.100
Preservation of RRF
As 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 counseling
In 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 1.2–1.3 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 day 106
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 <0.8 and 0.73 g/kg per
day, respectively.9,106 Furthermore, an intake of ≥1.0 g/kg
per day seems to be sufficient in nitrogen balance studies
of patients on peritoneal dialysis.34,107 These findings
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© 2012 Macmillan Publishers Limited. All rights reserved
therefore support the rationale for reducing the target
DPI to a minimum of 1.0 g/kg per day.106,108
Oral supplements
Various oral nutritional supplements that provide energy
or protein sources or a combination of both are avail-
able for patients on dialysis. Table 1 presents a summary
of studies that have examined the effects of oral supple-
ments on the nutritional status of patients on peritoneal
dialysis. 109–117 A nonrandomized study showed that
serum albumin levels and protein catabolic rate (PCR)
increased significantly after adding 0.1–0.3 g/kg per day
of high biological value protein to the diet of elderly
patients on peritoneal dialysis.109 Subsequently, random-
ized controlled trials showed that an increase in protein
intake using polymeric diets112 or an egg albumin supple-
ment 115 considerably increased serum albumin levels,
whereas other types of supplement, such as amino acid
tablets or protein drinks, did not.111,114 Nutritional sup-
plements also led to a significant improvement in serum
albumin levels in patients on dialysis, but only in those
on hemo­dialysis.116 Moreover, in a randomized crossover
study in patients on hemodialysis and peritoneal dialysis,
nPCR was stably maintained and serum albumin levels
were slightly increased in patients who received a protein
supplement, whereas both parameters were decreased in
patients who did not receive the protein supplement.117
Despite inconsistent results, oral nutritional supplements
are encouraged in clinical practice for patients with PEW
on peritoneal dialysis.
Oral appetite stimulants
Megestrol acetate is recommended for the treatment of
patients with anorexia and cancer or AIDS. This appe-
tite stimulant is an orally active, synthetic derivative of
naturally occurring progesterone that increases appetite
by stimulating neuropeptide Y in the hypothalamus and
exerts anti-inflammatory effects by downregulating
proinflammatory cytokines.118 Clinical experience with
megestrol acetate in patients on dialysis is limited. To our
knowledge, only three studies have examined the effects
of megestrol acetate in patients on peritoneal dialysis.
One of these studies showed that low-dose megestrol
(40 mg per day) administered for 4 months increased
appetite and serum albumin levels in 12 patients on
peritoneal dialysis and in four on hemodialysis.119 Two
subsequent studies using 160 mg �����������������
per day ���������
of meges-
trol for 1–23 months obtained similar findings. 120,121
Unfortunately, as all of these studies were uncontrolled,
the reported positive results need, in our opinion, further
confirmation through well-designed, controlled studies.
Furthermore, the long-term use of megestrol has raised
safety concerns as adverse effects, including thrombo­
embolic phenomena, uterine bleeding, peripheral edema,
hyperglycemia, hypertension and adrenal insufficiency,
have been widely reported.122
Amino acid solutions
A unique feature of peritoneal dialysis is the large loss
of 3–4 g per day of amino acids and 9–12 g per day of
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Table 1 | Effects of oral supplements on nutritional status in patients on peritoneal dialysis

Study Study type Population Interventions Follow-up Results
Shimomura Nonrandomized 36 Supplement of 0.1–0.3 g protein per kg 6 months serum albumin, prealbumin,
et al. (1993)109 controlled per day (n = 18); controls had no transferrin, plasma total amino acids,
supplement (n = 18) and the ratio of essential amino
acids to nonessential amino acids
Heaf et al. No control group 14 Commercial supplement with 40 g 10 weeks No change in serum albumin, DPI,
(1999)110 protein per day calorie intake and nPNA
Eustace et al. Randomized double 47 (18 on PD Oral essential amino acid tablets vs 3 months No change in serum albumin level or
(2000)111 blind placebo-controlled and 29 on HD) placebo grip strength; skinfold thickness
Aguirre Galindo Randomized 100 High protein diet (1.4 g/kg per day) 4 months serum albumin level and total
et al. (2003)112 (n = 50) vs calcium caseinate diet protein in both groups
(n = 50)
Boudville et al. Single blind crossover 13 on PD Commercial supplement with 475 kcal ND serum albumin level, total calorie
(2003)113 and 16.6 g protein and protein intake
Teixidó-Planas Randomized controlled 75 Commercial supplement with 20 g of 12 months No change in serum albumin level;
et al. (2005)114 protein per day high rate of noncompliance and
intolerance to commercial protein
supplement
González- Randomized controlled 30 Egg albumin supplement with 30 g 6 months serum albumin, total calorie and
Espinoza et al. protein per day (n = 13); control (n = 15) protein intake, and nPNA
(2005)115
Poole and No control group 190 (157 on 20–30 g protein and 500 kcal per day for 3 months serum albumin (HD only); no
Hamad HD and 33 on nondiabetics; 13.8 g protein and significant improvement in PD
(2008)116 PD) 250 kcal per day for diabetics
Moretti et al. Randomized crossover 49 (6 on PD PD: 105 g protein per week; HD: 45 g 12 months No change nPCR and serum
(2009)117 and 43 on HD) protein per week 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.

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 (72–78%) 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 (Table 2).125–134 However, these find-
ings are not consistent with those from other studies
(Table 3).135–139 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 treatments
As 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 (Table 4). As mentioned earlier, altered growth
hormone–IGF‑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

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Table 2 | Studies showing positive effects of 1.1% amino acid-based solution in patients on peritoneal dialysis
Study Study type Population Interventions Follow-up Result
Bruno et al. Crossover 6 One exchange of a 1.1% amino 6 months nitrogen balance and MAMC; serum
(1989)125 acid-based solution bicarbonate
Arfeen et al. Case series 7 Two exchanges of a 1.1% amino 2 months serum albumin; serum bicarbonate
(1990)126 acid-based solution
Kopple et al. Case series 19 1–2 exchanges of a 1.1% amino 20 days nitrogen balance, BUN and transferrin;
(1995)127 acid-based solution serum bicarbonate
Faller et al. Case series 15 One exchange of a 1.1% amino 3 months serum albumin, BUN and transferrin;
(1995)128 acid-based solution no change in serum bicarbonate
Chertow et al. Observational 183 One exchange of a 1.1% amino Mean 6.6 months serum albumin; no change in serum
(1995)129 acid-based solution bicarbonate
Misra et al. Randomized 18 One exchange of a 1.1% amino 6 months Improved nutrition score; no change in serum
(1996)130 crossover acid-based solution albumin and transferrin; serum albumin in
patients with baseline albumin <30.0 g/l
Jones et al. Randomized 134 One or two exchanges of a 1.1% 3 months IGF-I, serum albumin, prealbumin, and
(1998)131 controlled amino acid-based solution (n = 71); transferrin; serum bicarbonate
control (n = 63)
Taylor et al. Observational 22 One exchange of a 1.1% amino Mean 13.6 months serum albumin and nPCR; one episode
(2002)132 acid-based solution of peritonitis per 23 treatment months;
4% annual mortality rate
Li et al. Randomized 60 One exchange of a 1.1% amino 36 months nPNA and DPI; no change in mortality rate
(2003)133 controlled acid-based solution (n = 30); and incidence of peritonitis
control (n = 30)
Park et al. Observational 43 One exchange of a 1.1% amino 12 months LBM, hand grip strength, nPNA and IGF‑I;
(2006)134 acid-based solution no change in serum albumin, prealbumin and
DPI; serum bicarbonate
Abbreviations: BUN, blood urea nitrogen; DPI, dietary protein intake; IGF‑I, insulin-like growth factor I; LBM, lean body mass; MAMC, mid-arm muscle circumference; nPNA, normalized protein
nitrogen appearance; nPCR, normalized protein catabolic rate.

Table 3 | Studies showing neutral effects of 1.1% amino acid-based solution in patients on peritoneal dialysis
Study Study type Population Interventions Follow-up Results
(months)
Young et al. Case series 8 One exchange of 1.1% amino 3 No change in serum albumin or
(1989)135 acid-based solution prealbumin; no change in serum
bicarbonate; transferrin
Dombros et al. Case series 5 One exchange of 1.1% amino 6 No change in serum albumin,
(1990)136 acid-based solution transferrin, DPI, DEI and skinfold
thickness; no change in serum
bicarbonate
Dibble et al. Case series 8 One exchange of 1.1% amino 3 No change in total energy intake,
(1990)137 acid-based solution MAMC and skinfold thickness
Maurer et al. Randomized 18 One or two exchanges of a 6 No change in serum albumin,
(1996)138 controlled 1.1% amino acid-based transferrin, and LBM; no change
solution (n = 9); control (n = 9) in serum bicarbonate
Grzegorzewska Case series 16 One exchange of 1.1% amino 6 No change in serum albumin, LBM,
et al. (1999)139 acid-based solution with skinfold thickness, DPI and DEI;
antacid (n = 8); control (n = 8) no change in serum bicarbonate
Abbreviations: DEI, dietary energy intake; DPI, dietary protein intake; LBM, lean body mass; MAMC, mid-arm muscle circumference.

on peritoneal dialysis.142–145 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.147–149 In a double-blind, random-
ized controlled trial, treatment of patients on perito-
neal dialysis with oxymetholone for 6 months resulted
in a significant increase in serum albumin levels and

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Table 4 | Effects of hormonal treatments on nutritional status in patients on peritoneal dialysis

Study Study type Population Interventions Follow-up Results
Growth hormone
Ikizler et al. Crossover 10 rhGH 5 mg per day 7 days BUN and total UNA; no change in DPI, transferrin
(1994)142 and prealbumin
Kang et al. Case series 10 rhGH 10 IU/m2 weekly 12 weeks nitrogen balance and maximum oxygen
(1994)143 consumption capacity; BUN and total UNA
Ikizler et al. Crossover 10 rhGH 5 mg per day 7 days Essential amino acids in plasma and dialysate
(1996)144
Iglesias et al. Randomized rhGH group (n = 8); rhGH 0.2 IU/kg per day 4 weeks body weight, IGF‑I, and transferrin; BUN;
(1998)145 controlled control (n = 9) no change in DPI and serum albumin
IGF-I
Fouque et al. Case series 6 rhIGF‑I 100 μg/kg per 35 days nitrogen balance; BUN and urine nitrogen;
(2000)146 12 h no change in serum albumin, MAMC and skinfold
thickness
Androgen
Dombros Observational 13 Nandrolone decanoate 3 months serum albumin; no change in BUN
et al. 100–200 mg monthly
(1994)147
Johansen Randomized double- 29 (9 PD and 20 HD); Nandrolone decanoate 6 months LBM, serum creatinine, and functional
et al. blind placebo- androgen group (n = 14); 100 mg weekly improvement
(1999)148 controlled placebo (n = 15)
Navarro et al. Randomized Androgen group (n = 13); Nandrolone decanoate 6 months serum albumin, prealbumin, transferrin, body
(2002)149 controlled EPO group (n = 14) 200 mg weekly weight, MAMC and skinfold thickness; BUN and
total UNA
Aramwit et al. Randomized double- Oxymetholone (n = 11); Oxymetholone 50 mg 6 months serum albumin and LBM
(2010)150 blind placebo- placebo (n = 13) twice daily
controlled
Ghrelin
Wynne et al. Randomized double- 9 A single injection of – Energy intake; appetite, but no difference
(2005)152 blind crossover ghrelin (3.6 nmol/kg) between ghrelin and saline group
Ashby et al. Randomized double- 12 (3 on PD and 9 on Ghrelin (3.6 nmol/kg) 7 days Energy intake; appetite
(2009)153 blind crossover HD) daily
Abbreviations: BUN, blood urea nitrogen; DPI, dietary protein intake; EPO, erythropoietin; HD, hemodialysis; LBM, lean body mass; MAMC, mid-arm muscle circumference; PD, peritoneal
dialysis; rHGH; recombinant human growth hormone; rhIGF‑I, recombinant human insulin-like growth factor I; UNA, urea nitrogen appearance.

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 studies—both of
randomized, double-blind, crossover design and per-
formed by the same group—have 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 7 days 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 acidosis
A 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 bene­f icial effects of acidosis correction on nutri-
tional status were mediated by the downregulation of
branched-chain amino acid degradation and muscle
proteo­lysis via the ubiquitin–proteasome system. 156
In addition, another randomized controlled trial
showed that treatment with oral sodium bicarbonate
for 12 months resulted in increases in SGA score and
nPNA in patients on peritoneal dialysis with acidosis
and Kt/V <2.1.157 Furthermore, patients treated with
pure bicarbonate-­buffered peritoneal dialysis solution
exhibited an improved nPCR compared with those
treated with lactate-buffered solution. Presumably, the
bicarbonate-buffered solution was better able to correct
acidosis than the lactate solution.158 Interestingly, even
within normal pH range, a greater positive nitrogen
balance was achieved in patients with a high-normal
(7.44) arterial pH than in those with a low-normal (7.37)
arterial pH.159 In line with these studies, the KDOQI
guidelines recommend a therapeutic target of bicarbon-
ate levels of ≥22 mmol/l in patients with ESRD who are
maintained on dialysis.30

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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
<60 years and 30–35 kcal/kg body weight for patients
>60 years
Protein intake 1.2–1.3 g/kg body weight per day*
■■ Oral nutritional supplements
Peritoneal dialysis-related 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,
protein–energy wasting.
Conclusions
Improving the poor nutritional status of patients with
PEW on peritoneal dialysis is difficult owing to the
multi­f actorial 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 (Box 2). 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.
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”, “protein–energy 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”.

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Author contributions
All authors contributed equally to all aspects of the
article.