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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 mortality 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 prevention 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 peritoneal dialysis10 and include inflammation, inadequate
protein and calorie intake, loss of appetite, loss of residual renal function (RRF), loss of protein during dialysis,
psychosocial factors, physical inactivity and comorbid
Competing interests
The authors declare no competing interests.
Nomenclature
Malnutrition literally means bad nutrition and is usually
considered to entail undernutrition, which is characterized 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 malnutrition.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, including uremic malnutrition, uremic cachexia, protein
energy malnutrition, malnutritioni 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
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 conditions 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
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
dshan@yuhs.ac
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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 breakdown 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 signaling through the hypothalamic melanocortin 4 receptor improved uremic cachexia in a mouse model. 22
Furthermore, visfatin, a newly identified adipocytederived 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 peritoneal 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, nutritional status and inflammation were improved, whereas
fluid overload resulted in worse nutritional status and
promoted inflammation.28
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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 stimulating 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 appetite.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 solution might also influence appetite: in a rat model, a
bicarbonatelactate solution suppressed appetite to
a lesser extent than a lactate solution. 45 No clinical
evidence, however, exists to support this finding.
Inflammation
Loss of nutrients
into dialysate
Inadequate dialysis
Loss of residual
renal function
Anorexia
Inadequate
nutrient intake
Proteinenergy
wasting
Abdominal discomfort
induced by dialysate
Hypercatabolism
Chronic acidosis
Comorbid conditions:
diabetes mellitus,
cardiovascular disease,
infection
Peritonitis
Bioincompatible
solution?
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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) <38g/l
Serum prealbumin level (transthyretin) <30mg/dl
Serum cholesterol level <2.59mmol/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 <22kg/m2 65years, <23kg/m2 >65years (a lower BMI might be
desirable for certain Asian populations; weight must be edema-free mass)
Unintentional weight loss over time: 5% over 3months or 10% over 6months
Total body fat percentage <10%
Muscle mass
Muscle wasting: reduced muscle mass 5% over 3months or 10% over
6months
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 <0.80g/kg per day for at least 2months (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 <25kcal/kg per day for at least 2months
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, proteinenergy 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 IGFI
and growth hormone.37
Possible mechanisms of acidosis-induced PEW are
protein degradation, protein breakdown from skeletal muscle and oxidation of branched-chain amino
acids,65 a decrease in albumin synthesis,66 and reduced
expression of IGFI and growth hormone. 67 Many
cross-sectional studies have shown a direct relationship
between the severity of metabolic acidosis and nutritional status in patients with CKD.68 We observed that
patients on peritoneal dialysis with serum bicarbonate
levels of 1820mmol/l (associated with mild to moderate acidosis) had a favorable nutritional status.69,70
However, detailed analysis revealed that patients with
severe metabolic acidosis (that is, serum bicarbonate
levels <18mmol/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 associated 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
166 | MARCH 2012 | VOLUME 8
does not prove causality. The therapeutic target of bicarbonate levels 22mmol/l as suggested by the KDOQI
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
IGFI occurs in patients who have an abnormal growth
hormoneIGF axis despite normal or high levels of
endogenous growth hormone and IGFI.71 Furthermore,
high levels of IGF-binding proteins in these patients
reduces the amount of free IGFI.71 As growth hormone
exerts an anabolic effect and thereby induces protein
preservation and denovo protein synthesis,72 the abnormal growth hormoneIGF axis in uremia shifts the metabolic 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
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
25years 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 20days and can
be affected by inflammation, losses into dialysate and
fluid status, levels of serum albumin should be interpreted with caution when diagnosing PEW. 13,28,75 By
contrast, prealbumin has a relatively short half-life (of
approximately 2days), and so is considered to be a more
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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 mortality.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 appropriate. 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, interpretation of parameters of muscle mass in patients on peritoneal dialysis should be made after a careful consideration
of fluid status.
Dietary intake
Dietary intake as assessed by dietary diaries and interviews, even when a dietitian is involved, can be subjective 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
3day 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
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 creatinine 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 dialysis dose and improved nutritional status. To date, only
one prospective, randomized study has investigated the
link between dialysis dose and nutritional status; increasing Kt/V from 1.82 to 2.02 over 12months resulted
in an increase in nPNA from 1.10g/kg to 1.24g/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 dialysis 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 dialysis adequacy. Alternatively, combined peritoneal dialysis
and hemodialysis therapy might be helpful in improving nutritional status. Indeed, nPNA, creatinine generation 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 RRF
As loss of RRF is associated with deterioration in nutritional status, preservation of RRF could be assumed
to maintain nutritional status. Prospective, randomized 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 nutritional status as nutritional intake was affected to a greater
extent by RRF than by peritoneal dialysis solute clearance,11 which supports the findings from a previous
study.101 Given the large contribution of RRF to nutritional status and patient outcome, various efforts to preserve RRF in patients on dialysis should be an essential
part of PEW prevention strategies.
Dietary counseling
In patients on peritoneal dialysis, regular and comprehensive assessments to identify factors that cause PEW
are mandatory. Of note, only 39% of 266 patients on peritoneal dialysis complied with a DPI of 1.2g/kg per day as
recommended by the KDOQI guidelines.102 Therefore,
dietary counseling might be useful if inadequate nutritional intake is a problem. Indeed, a marked improvement 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 demonstrated 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 1.21.3g/kg per day is generally recommended for patients on peritoneal dialysis, the optimal
target has not yet been determined. In fact, the European
guidelines suggest a protein intake 1.0g/kg per day 106
and a study of Chinese patients on peritoneal dialysis
showed that DPI >0.94g/kg per day was associated with
favorable nutritional status and long-term outcomes.9
Interestingly, both this study and the European guidelines warned against lower DPIs of <0.8 and 0.73g/kg per
day, respectively.9,106 Furthermore, an intake of 1.0g/kg
per day seems to be sufficient in nitrogen balance studies
of patients on peritoneal dialysis.34,107 These findings
168 | MARCH 2012 | VOLUME 8
Oral supplements
Various oral nutritional supplements that provide energy
or protein sources or a combination of both are available for patients on dialysis. Table1 presents a summary
of studies that have examined the effects of oral supplements on the nutritional status of patients on peritoneal
dialysis. 109117 A nonrandomized study showed that
serum albumin levels and protein catabolic rate (PCR)
increased significantly after adding 0.10.3g/kg per day
of high biological value protein to the diet of elderly
patients on peritoneal dialysis.109 Subsequently, randomized controlled trials showed that an increase in protein
intake using polymeric diets112 or an egg albumin supplement 115 considerably increased serum albumin levels,
whereas other types of supplement, such as amino acid
tablets or protein drinks, did not.111,114 Nutritional supplements 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 appetite 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
(40mg per day) administered for 4months increased
appetite and serum albumin levels in 12 patients on
peritoneal dialysis and in four on hemodialysis.119 Two
subsequent studies using 160mg
per day
of megestrol for 123months 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 34g per day of amino acids and 912g 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
etal. (1993)109
Nonrandomized
controlled
36
6months
Heaf etal.
(1999)110
No control group
14
10weeks
Eustace etal.
(2000)111
Randomized double
blind placebo-controlled
47 (18 on PD
and 29 on HD)
3months
Aguirre Galindo
etal. (2003)112
Randomized
100
4months
Boudville etal.
(2003)113
13 on PD
ND
Teixid-Planas
etal. (2005)114
Randomized controlled
75
12months
GonzlezEspinoza etal.
(2005)115
Randomized controlled
30
6months
Poole and
Hamad
(2008)116
No control group
190 (157 on
HD and 33 on
PD)
3months
Moretti etal.
(2009)117
Randomized crossover
49 (6 on PD
and 43 on HD)
12months
Abbreviations: DPI, dietary protein intake; HD, hemodialysis; ND, not determined; nPNA, normalized protein nitrogen appearance; nPCR, normalized protein catabolic rate; PD, peritoneal dialysis.
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, IGFI and androgenic anabolic steroids (Table4). As mentioned earlier, altered growth
hormoneIGFI axis and growth hormone resistance are
potential mechanisms for PEW in patients on dialysis;
nearly all of the studies that have evaluated the nutritional 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 etal.
(1989)125
Crossover
6months
Arfeen etal.
(1990)126
Case series
2months
Kopple etal.
(1995)127
Case series
19
20days
Faller etal.
(1995)128
Case series
15
3months
Chertow etal.
(1995)129
Observational
183
Mean 6.6months
Misra etal.
(1996)130
Randomized
crossover
18
6months
Jones et al.
(1998)131
Randomized
controlled
134
3 months
Taylor etal.
(2002)132
Observational
22
Mean 13.6months
Li etal.
(2003)133
Randomized
controlled
60
36months
Park etal.
(2006)134
Observational
43
12months
Abbreviations: BUN, blood urea nitrogen; DPI, dietary protein intake; IGFI, 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
(months)
Results
Young etal.
(1989)135
Case series
Dombros etal.
(1990)136
Case series
Dibble etal.
(1990)137
Case series
Maurer et al.
(1996)138
Randomized
controlled
18
Grzegorzewska
etal. (1999)139
Case series
16
Abbreviations: DEI, dietary energy intake; DPI, dietary protein intake; LBM, lean body mass; MAMC, mid-arm muscle circumference.
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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
Ikizler etal.
(1994)142
Crossover
10
7days
Kang etal.
(1994)143
Case series
10
12weeks
Ikizler etal.
(1996)144
Crossover
10
7days
Iglesias etal.
(1998)145
Randomized
controlled
4weeks
Case series
35days
Dombros
etal.
(1994)147
Observational
13
Nandrolone decanoate
100200mg monthly
3months
Johansen
etal.
(1999)148
29 (9 PD and 20 HD);
androgen group (n=14);
placebo (n=15)
Nandrolone decanoate
100mg weekly
6months
Navarro etal.
(2002)149
Randomized
controlled
Nandrolone decanoate
200mg weekly
6months
Aramwit etal.
(2010)150
Oxymetholone (n=11);
placebo (n=13)
Oxymetholone 50mg
twice daily
6months
Wynne etal.
(2005)152
A single injection of
ghrelin (3.6nmol/kg)
Ashby etal.
(2009)153
12 (3 on PD and 9 on
HD)
Ghrelin (3.6nmol/kg)
daily
7days
Growth hormone
IGF-I
Fouque etal.
(2000)146
Androgen
serum albumin; no change in BUN
Ghrelin
Energy intake; appetite, but no difference
between ghrelin and saline group
Energy intake; appetite
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; rhIGFI, recombinant human insulin-like growth factor I; UNA, urea nitrogen appearance.
Correction of acidosis
A small study of seven patients on peritoneal dialysis
showed a decrease in protein degradation with correction 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
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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 35kcal/kg of body weight for patients
<60years and 3035kcal/kg body weight for patients
>60years
Protein intake 1.21.3g/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
*1.0g/kg body weight per day can be acceptable unless there is
evidence of declining nutritional status. Abbreviation: PEW,
proteinenergy 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 counseling 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 importance given the fact that inflammation is a key mediator
of PEW. However, a paucity of data are available concerning the effect of anti-inflammatory therapies on
nutritional status.
1.
2.
3.
4.
5.
6.
12.
13.
14.
15.
16.
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2012 Macmillan Publishers Limited. All rights reserved
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17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69.
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70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
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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 3year, 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 acidbased dialysis solutions. Kidney Int. Suppl. 103,
S110S114 (2006).
135. Young, G.A. etal. The use of an
aminoacidbased 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) patients
no effect on nutritional status. Perit. Dial. Int. 10,
7984 (1990).
137. Dibble, J.B., Young, G.A., Hobson, S.M. &
Brownjohn, A.M. Aminoacidbased continuous
ambulatory peritoneal dialysis (CAPD) fluid over
twelve weeks: effects on carbohydrate and lipid
metabolism. Perit. Dial. Int. 10, 7177 (1990).