REVIEW

Systematic Review of Evidence for the Use

of Intradialytic Parenteral Nutrition in
Malnourished Hemodialysis Patients
Mhairi K. Sigrist, BSc, PhD,* Adeera Levin, MD, FRCP,*
and Aaron M. Tejani, BSc(pharm), PharmD, ACPR†

Objective: Intradialytic parenteral nutrition (IDPN) is widely used to treat malnourished hemodialysis (HD) patients.
However, the benefits of this treatment are unknown. Moderate protein-energy malnutrition (PEM) is thought to affect
15% to 43% of maintenance HD patients, and is independently associated with mortality in this population. This
study systematically reviews the current literature, to assess whether IDPN improves survival, quality of life, or
nutritional status in those receiving maintenance HD.
Methods: Two investigators undertook a formal systematic review of the literature, using the following key search
words: intradialytic parenteral nutrition or intradialytic total parenteral nutrition plus any combination of renal dialysis
or kidney-failure or chronic kidney disease and parenteral nutrition or intravenous nutrition or intravenous feeding.
Results: The search identified three suitable randomized, controlled trials, only one of which investigated hard
clinical endpoints. There were insufficient data to undertake a meta-analysis.
Conclusions: The evidence from clinical studies is insufficient to demonstrate either a net benefit or a net harm
associated with the providing IDPN to malnourished HD patients. We recommend that any patient in whom IDPN
was deemed necessary be entered into a clinical trial or registry, to record hard clinical outcomes associated with
the use of this treatment.
Ó 2010 by the National Kidney Foundation, Inc. All rights reserved.

M AINTENANCE HEMODIALYSIS (HD)

is associated with a 20% annual mortality
rate. Moderate protein-energy malnutrition
(PEM) is thought to affect 15% to 43% of mainte-
nance HD patients and is independently associated
with mortality in this population.1–5 Malnutrition
in HD patients has a multitude of often interrelated
causes. Chronic systemic inflammation, comorbid
*Department of Nephrology, University of British Columbia,
St. Paul’s Hospital, Vancouver, British Columbia, Canada.
†Clinical Research and Drug Information, Fraser Health Phar-
macy Services, Fraser Valley, British Columbia, Canada.
Address reprint requests to Mhairi K. Sigrist, Department of Ne-
phrology, St. Paul’s Hospital, University of British Columbia, Prov-
idence Health, 1081 Burrard St., Rm. 6010A, Vancouver, British
Columbia, Canada. V6K 1C6. E-mail: msigrist@
providencehealth.bc.ca
Ó 2010 by the National Kidney Foundation, Inc. All rights
reserved.
1051-2276/10/2001-0001$36.00/0
doi:10.1053/j.jrn.2009.08.003
conditions, and metabolic acidosis result in in-
creased catabolism and suppression of appetite.6,7
The oral intake of many dialysis patients is insuffi-
cient to meet the increased nutritional needs asso-
ciated with dialysis, because of poor appetite and
missed meals due to dialysis and dialysis transit
times coinciding with mealtimes. In addition, de-
layed dialysis starts and overzealous attempts to
control protein intake predialysis can compromise
an individual’s nutritional status before dialysis is
initiated.8
The first-line treatment for PEM is to encour-
age increased nutrition through the enteral route,
using advice tailored to an individual’s require-
ments and dietary habits. Intradialytic parenteral
nutrition (IDPN) has been used as a last resort
for severe PEM in patients on dialysis since the
mid-1970s, and is widely believed to promote im-
proved nutritional status. Intradialytic parenteral
nutrition has the advantages of delivering required
nutrients intravenously in a low-volume solution.

Journal of Renal Nutrition, Vol 20, No 1 (January), 2010: pp 1–7 1

2 SIGRIST ET AL
However, it is expensive (costing $312 [Canada]
month per patient in British Columbia). Because
it is intravenously administered, IDPN is not with-
out risk, and can be time-consuming for dialysis
nurses. Further, if the root cause of malnutrition
is chronic inflammation and cachexia, it is unclear
whether increased nutrient delivery in any form
will alter the outcomes of these individuals. At
present, there appears to be a lack of evidence
from randomized, controlled trials (RCTs) dem-
onstrating the effectiveness of IDPN in altering
the clinical outcomes of its recipients.
Several reviews in the renal literature concerned
the use of IDPN. These reviews were limited by
a lack of systematic approaches to the literature,
and the inclusion of nonrandomized and noncon-
trolled trials. In addition, these reviews tended to
rely on surrogate markers of nutrition, e.g.,
amino-acid loss, rather than clinically important
outcomes, e.g., an increased ability to perform ac-
tivities of daily living. Foulks published the last
good-quality, systematic review in 1999, when
few RCTs of IDPN had been published.9 In our
current era of accountability and evidence-
informed care, a full systematic review of the litera-
ture is important, to guide the appropriate use of this
expensive treatment. This study was to undertake
a formal, systematic review of the literature, to assess
whether IDPN improves survival, quality of life, or
nutritional status in recipients of maintenance HD.
Methods
Only full trial reports of RCTs or systematic re-
views of RCTs were included for critical appraisal
and analysis. Abstracts were not included, because
they did not provide enough information for ade-
quate assessment of the validity or reliability of
study findings. We included RCTs if they specif-
ically enrolled malnourished patients on HD
who were randomized to either IDPN (including
full IDPN or amino acids plus carbohydrates only)
or any form of enteral or oral nutrition. A hierar-
chy of clinically important outcomes (in descend-
ing order of importance) was chosen a priori to
guide the analysis: total mortality, nonfatal serious
adverse events, quality of life, a validated measure
to assess activities of daily living/muscle weakness,
and improved nutritional status (as measured
by body weight, arm-muscle circumference,
triceps-skinfold thickness, or serum albumin).
Search Strategy
The search included the following electronic
databases: Pub Med (1950 to July 2009), EMBASE
(1988 to July 2009), CINAHL (1982 to July 2009),
and the Cochrane Central Register of Controlled
Trials (up to July 2009). Key search words in-
cluded: intradialytic parenteral nutrition or intra-
dialytic total parenteral nutrition. In addition, we
used any combination of renal dialysis or kidney-
failure or chronic kidney disease and parenteral
nutrition or intravenous nutrition or intravenous
feeding. No language restrictions were applied to
the search. For systematic reviews, a search was
conducted in the following databases: Centre for
Reviews and Dissemination (up to July 2009),
Pub Med (systematic review filter up to July
2009), and the Cochrane Database of Systematic
Reviews (up to July 2009).
Data Extraction
Two reviewers independently extracted the data
from included trials, using a standardized data-
extraction form. In situations where a discrepancy
arose, a third reviewer was consulted.
Statistical Analyses
Insufficient data were available to warrant
a meta-analysis. Instead, a compilation of results
extracted from the RCTs is given in Table 1.
Results
Search Findings
After duplicates were removed, the initial key-
word search of each database identified 112
abstracts. Both reviewers screened all abstracts of
identified citations. Six potentially suitable
RCTs10–15 and five potential systematic re-
views9,16–19 were then retrieved in full, based on
this first screening. Reference lists of these papers
were hand-searched to identify relevant trials for
the present review. Four trials that met inclusion
criteria were identified in the reviews.20–23 Both
reviewers independently perused each of these
original articles, to determine which trials met
all the inclusion criteria.
Only three of the identified studies met the
inclusion criteria as RCTs. The results of these
studies are summarized in Table 1. Of these studies,
only that of Cano et al. in 2007 included mortality
as a primary outcome.10 That study reported
Table 1. Summary of Results From RCTs
Outcome
Design
n (subjects)/duration
Intervention
Comparator
Primary outcome
All-cause mortality
Serious adverse events
Quality of life/ADLs
Body-weight change (% 6 SD)
Arm-muscle circumference change
(% of normal values)
Triceps skinfold-thickness change
Serum albumin change
ADA, activities of daily living.
Wolfson et al., 198215 Cano et al., 199020 Cano et al., 200710
Open-label, randomized, crossover Open-label, parallel group, Open-label, parallel group,
IDPN IN MALNOURISHED HEMODIALYSIS PATIENTS
randomized controlled trial (no randomized controlled trial
multiplicity adjustment)
8 men/23300-minute HD sessions 26/84 days after HD 186/2 years
Essential/nonessential amino acids Predialytic parenteral nutrition plus Intradialytic parenteral nutrition plus
plus glucose solution usual diet oral supplements
Normal saline Usual diet only Oral supplements only
Plasma amino-acid levels No primary outcome was identified All-cause mortality
NR NR IDPN, 40/93; control subjects, 36/93
NR NR NR
NR NR Karnofsky Score; nochange in score
for either group, butno details were
provided
NR PDPNchange, 2.00% 6 Details not reported, but IDPN was
1.65%Control change, 21.50% 6 claimed beneficial
3.50%Difference (P , .01), 3.50%
NR PDPNchange, 3.676 4.60Control NR
change, 20.3663.41Difference (P
, .025), 4.03
NR PDPN, 2.006 7.08Control subjects, NR
23.14610.54Difference (P5NS),
5.14
NR PDPN, 0.956 2.19Control subjects, Details not reported, but IDPN was
20.4362.36Difference (P , .05), claimed beneficial
1.38
3
 4
Table 2. Studies Excluded Because Study Design Did Not Meet Inclusion Criteria
Citation Population Design Interventions Follow-Up Conclusion Reason for Exclusion

Capelli et al.,11 Malnourished Nonrandomized IDPN(n550).Control 12 months Using IDPN to treat low Subjects were not
AmJ Kidney Dis chronic HD. cohort study. group (n531) did albumin led to better randomized, and
23:808-818, 1994 not receive IDPN. survival rates than in study was not
untreated control controlled.
subjects.
Chertow et al.,12 All HD patients Retrospective, IDPN(n51679).Control 12 months In HD patients with Retrospective study.
Am J Kidney Dis receiving dialysis nonrandomized group (n522,517) serum albumin Subjects were not
24:912-920, 1994 through national cohort study. did not receive IDPN. ,3.3 g/dL or lower, randomized, and
medical care. odds ratio of death study was not
was significantly controlled.
reduced in individuals
receiving IDPN.
Dezfuli et al.,24 HD patients with Nonrandomized IDPN(n5196).Nocontrol 3-12 months 72% of subjects Subjects were not
JRen Nutr hypoalbuminemia cohort study. group was used. responded to IDPN randomized, and
19:291-297, 2009 (,3.5 g/dL). with an increase in study was not
serum albumin. Mean controlled.

SIGRIST ET AL
increase in albumin
was 0.4 g/dL.
Guarnieri et al.,21 Patients receiving Randomized, Intravenous essential 3 times/week Limited benefits Subjects were treated
Am J Clin Nutr regular HD for controlled trial. amino acids 6 for 2 months with short-term with amino acids
33:1598-1607, 1980 306 23 SD months. histidine or supplementation of only, and not
intravenous amino-acid solutions. complete IDPN.
solution of essential
and nonessential
amino acids.Control
group given
intravenous solution
of 5%
glucose.Totaln518,
number in each
group not stated.
Hecking et al.,22 Stable chronic Randomized Essential amino-acid or 6 months Essential amino acids Subjects were treated
Proc Clin Dial home HD patients. crossover trial. placebo solution for 3 may improve physical with amino acids
Transplant Forum months (n513), after state and protein only, and not
157-161, 1977 which they were levels in catabolic complete IDPN.
crossed over. HD patients only.
Hiroshige et al.,23 Elderly, chronic, Nonrandomized, IDPN(n510).Control 12 months IDPN prevents muscle Subjects were not
Nephrol Dial stable HD patients. controlled trial. group had refused catabolism, and randomized.
Transplant IDPN (n5 18). promotes protein and
13:2081-2087, 1998 fat accumulation.
(Continued )
 IDPN IN MALNOURISHED HEMODIALYSIS PATIENTS 5

marginally higher 2-year mortality in the IDPN

group, compared with subjects who received
Reason for Exclusion

Subjects were treated

oral supplementation alone. The authors reported

with amino acids

Subjects were not

complete IDPN.
that those who received IDPN had a higher body
malnourished.

only, and not

weight and higher level of albumin, compared
with the group that received oral supplementa-
tion alone. However, the actual numbers were
not reported in the paper. Therefore, it is not pos-
sible to perform a meta-analysis of these results.
higher serum albumin

amino-acid solutions.
supplementation had
receiving amino-acid

and transferrin levels

Nor is it possible to determine the magnitude of

in nutritional status.
No significant change

effective than oral

comfortable and benefit. Interpretations of the results from this pa-
Intravenous amino
However, those
Conclusion

acids are more

per are limited by the absence of a control group

at 3 months.

receiving no nutritional support.

In 1990, Cano et al. studied the effects of IDPN
versus no IDPN in addition to usual diet over
a 12-week period.20 Here, the authors found a sig-
nificant improvement in body weight (a greater
Follow-Up

increase in mean percent change from a baseline

3 months

4 months

of 3.5% in body weight, P ,.01), serum albumin

(a greater increase in mean change from a baseline
of 1.38, P ,.05), and midarm muscle circumfer-
Table 2. Studies Excluded Because Study Design Did Not Meet Inclusion Criteria (Continued )

subjects (n57) did not

ence (a greater increase in mean change from

acids (n510).Control

essential amino-acid
receive amino acids.

amino-acid solution

a baseline of 4.03%, P ,.025) in those individuals

(n56).Intravenous
Intravenous amino
Interventions

solution (n514).

receiving IDPN. Although they were statistically

significant, it is unclear whether these improve-
Oralessential

ments in outcome measures with IDPN were

clinically relevant or perceptible. The only other
identified RCT was published by Wolfson
et al.15 Those authors did not report any clinically
relevant outcomes, but only changes in serum
amino-acid concentrations.15 The information
controlled trial.

if randomized.
Design

Controlled trial,

from these studies was insufficient to conduct

Randomized,

a meta-analysis of the data.

unclear

Table 2 shows the results of studies initially

identified as RCTs, but excluded upon full read-
ing from the systematic review because of ele-
ments in their study design. In the absence of
Nondiabetic stable HD

RCTs, these studies provide limited evidence

patients for $12
Population

for the use of IDPN. Perhaps the most important

Malnourished,

of these studies was a nonrandomized, retrospec-

chronic HD
patients.
months.

tive analysis of 1679 subjects who received IDPN,

as registered in the Medicare database.12 The au-
thors reported that, compared with the other
22,517 patients receiving HD, those individuals
Oguz et al.,14 Nephron

with serum albumin levels #3.3 g/dL and receiv-

71:765-775, 2000

89:224-227, 2001

ing IDPN had a significantly reduced odds ratio of

AmJ Clin Nutr
13

death. Using a similar study design, Capelli et al.

Navarro et al.,

found that using IDPN to treat low albumin levels

led to better survival rates than in untreated con-
Citation

trols.11 However, the difference was significant

only in nondiabetic subjects.11 Dezfuli et al. pub-
lished a large-scale study of IDPN in 196 HD
6 SIGRIST ET AL
patients, but this study was disappointing in both
study design and outcomes reported.24 The au-
thors demonstrated that the majority of subjects
with hypoalbuminemia respond to IDPN with
an increase in serum albumin, and the lower the al-
bumin to start with, the greater the response. Sub-
jects were recruited based on serum albumin level,
a surrogate for malnutrition, with no other assess-
ment of nutritional status reported. Despite large
numbers of recruited subjects, there was no report-
age of tolerance or adverse events associated with
IDPN in this population. Finally, this study did
not describe any hard clinical outcomes. We would
encourage this group to publish the effects of the
observed changes in serum albumin on mortality
in the coming years. Hiroshige et al. demonstrated
that 12 months of IDPN prevented muscle catab-
olism and promoted protein and fat accumula-
tion.23 The study by Navarro et al. was excluded
from the systematic review because their subjects
were not malnourished.13 The remaining three
studies shown in Table 1 were excluded at they
did not use full IDPN solutions, but only intrave-
nous infusions of amino acids.14,21,22
Discussion
Despite the availability of IDPN for over 30
years, there remains a lack of well-conducted
RCTs to guide the use of this treatment in the
clinical setting. At present, the evidence from clin-
ical studies is insufficient to demonstrate either
a net benefit or a net harm associated with provid-
ing IDPN to malnourished HD patients. In part,
this is attributable to difficulties in designing suit-
able studies, because it is unethical to withhold
nutrition for any period of time. A single well-
designed study was published on this topic to
date.10 The design by Cano et al.20 was clearly
well thought through and executed, and the fol-
low-up was of reasonable length. Unfortunately,
they demonstrated no survival advantage of treat-
ing malnutrition with IDPN. Either the interven-
tion itself is not of value, the interventions studied
are of equal value (i.e., oral nutrition supplemen-
tation is of equal value to IDPN), or else malnutri-
tion is a marker for other comorbidities that affect
the outcome of interest (survival), and fixing the
malnutrition per se does not alter outcomes.
That study did highlight the ability to provide ad-
equate oral supplementation in malnourished HD
patients, and the importance of that as a marker,
given that the group of subjects receiving oral
nutritional supplementation had a nonsignificant
survival advantage over those receiving IDPN.
A number of studies regarding IDPN were ex-
cluded from our search on first screening because
of their study design. However, many of these
studies are widely quoted in the literature, and
therefore we include these in this discussion. Pu-
pim et al. published a series of studies investigating
the acute intradialytic effects of IDPN on the
protein metabolism of HD patients.25–27 Of par-
ticular interest, the most recent of these demon-
strated that oral supplementation confers
anabolic benefits superior to those of IDPN after
dialysis.27 However, these studies were excluded
from the analysis because of their inherent risk of
bias (and subsequent poor validity and reliability)
due to their nonrandomized study design.28 Over-
all, the data may well support oral supplementation
over intravenous supplementation, although cau-
tion in drawing this conclusion remains.
When prescribing this treatment in the clinical
setting, clinicians and dietitians should bear in
mind that no conclusive evidence indicates that
IDPN will benefit the patient. Nor is there evi-
dence that it will or will not cause the patient
harm. Given that IDPN has both cost and resource
implications, and given the lack of evidence for its
present use, we recommend that every patient in
whom there is thought to be a clinical need for
this treatment be entered into a clinical study, or
at least registered in a formal longitudinal cohort.
Only through a careful enunciation of criteria for
the commencement of IDPN, regular articulation
of expected goals of therapy, and measurement of
the attainment of those goals, can we begin collect-
ing data to guide practice more accurately. Ideally,
we recommend designing an adequately powered
multicenter RCT, where any HD patient deemed
to be malnourished according to predetermined
overt and reproducible criteria is randomly as-
signed to receive either oral supplementation or
IDPN for a period of 3 months to 1 year. This study
would involve the collection of hard clinical end-
points, including mortality, serious adverse events,
quality of life, activities of daily living, and anthro-
pometric measurements of nutritional status,
which would be collected every 3 months. Should
a RCT not be deemed feasible, then a formal reg-
istration should be undertaken of all patients com-
mencing nutritional supplementation, with
routine and common assessment protocols.
 IDPN IN MALNOURISHED HEMODIALYSIS PATIENTS
In conclusion, mortality is associated with mal-
nutrition in the HD population. Thus, an aggres-
sive approach to combating malnutrition appears
to be an important goal. Nonetheless, current
evidence does not support the use of IDPN in
chronic dialysis patients with normal gastrointesti-
nal function. Clear parameters and goals should be
established for the use of IDPN, or ideally, a large
multicenter, randomized trial should be under-
taken. We recommend that any patient in whom
IDPN is deemed necessary be entered into a clini-
cal trial or registry, to record hard clinical out-
comes associated with the use of this treatment.
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