Invited Review

Challenges of Providing Nutrition Support in the Outpatient

Dialysis Setting
Eileen Moore, CNSD, RD, LD*; and Joe Celano, MBA
*Parma DaVita Dialysis, Parma, Ohio; and INTRX HealthCare, New Orleans, Louisiana

malnourished.1 Although there is no single measure

to identify malnutrition in this population and multiple parameters have been used to assess for malnutrition, studies have elucidated nutrition markers
associated with morbidity and mortality.
Serum albumin levels 4 mg/dL have been shown
to be the strongest parameter associated with
increased death risk in a retrospective analysis of
over 12,000 patients.2 Serum transthyretin (TTR)
has recently been acknowledged as the single best
predictor of survival. A study of approximately 190
MHD and peritoneal dialysis (PD) patients followed
for 5 years found serum TTR levels of 30 mg/dL to
be the strongest variable that predicted mortality in
MHD patients.3 Another study of over 1600 MHD
patients determined by proportional hazards regression analysis that TTR provides prognostic value
independent of the serum albumin level and other
predictors of mortality in MHD.4 Despite the apparent strong association of malnutrition with morbidity and mortality, financial obstacles exist with
certain nutrition-support modes for the malnourished MHD patient, and optimal repletion mode(s)
have not been defined.

ABSTRACT: Malnutrition is prevalent in maintenance

hemodialysis (MHD) patients and has been strongly associated with increased morbidity and mortality. There are
numerous contributors to the development, occurrence,
and persistence of malnutrition in the MHD patient.
Intensive diet counseling and use of enteral supplements
may not be effective interventions for patients exhibiting
high nutrition risk. More aggressive nutrition options
such as enteral and parenteral support are less often used
and have associated risks. Intradialytic parenteral nutrition (IDPN) as a form of PN delivered during the dialysis
procedure is a convenient and attractive convention that
is underused because of its history and controversy.
There is a lack of randomized controlled trials demonstrating improved morbidity and mortality with all nutrition support interventions in MHD patients. This research
is particularly crucial for IDPN in order to render change
in Medicare reimbursement. Qualification of patients for
this therapy is difficult because of the very strict coverage
criteria. For those patients who do qualify for IDPN,
clinician nutrition support knowledge is essential for safe
administration of solutions and effective physical, metabolic, and nutrition management of the patient. Attention
to other factors that contribute to malnutrition in MHD
such as treatment adequacy and comorbid conditions is
important; however, the early detection of malnutrition in
the MHD patient with appropriate level of nutrition
intervention is critical. Future improved understanding of
the malnutrition of uremia will allow for development and
investigation of other strategies that are anti-catabolic or
anabolic.

Contributors to Malnutrition in MHD

There are numerous factors contributing to the
development, occurrence, or persistence of malnutrition in the MHD patient, including comorbidities,
intercurrent illness, hospitalization, infection, multiple medications, socioeconomic issues, isolation,
and depression. Factors related to the dialysis procedure itself contribute by rendering amino acid
losses of 5 8 g per dialysis session, with even
greater losses with use of high-efficiency dialyzers.
Reprocessing of the dialyzer is another source of
amino acid loss. A recent analysis determined that
10 g of amino acids may be lost after the 15th reuse
of the dialyzer.5 Finally, inadequate dialysis prescription noted by clearance parameters of Kt/V
1.2 or urine urea reduction (URR) 65% for thriceper-week MHD may influence progression of malnutrition. In a study of 55 MHD patients, a linear
relationship was demonstrated between Kt/V and
protein catabolic rate (nPCR), which reflects dietary
protein intake in steady state.6 Increasing dietary

It is estimated that approximately 40% of maintenance hemodialysis (MHD) patients exhibit some
degree of malnutrition, 10% of whom are severely

Correspondence: Eileen Moore, CNSD, RD, LD, Parma DaVita

Dialysis, 6735 Ames Drive, Parma, OH 44129. Electronic mail
may be sent to emmoore@davita.com.
0884-5336/05/2002-0202$03.00/0
Nutrition in Clinical Practice 20:202212, April 2005
Copyright 2005 American Society for Parenteral and Enteral Nutrition

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PROVIDING NUTRITION SUPPORT IN OUTPATIENT DIALYSIS

protein as counseled was ineffective until the dose of

dialysis increased first.
Perhaps the most prevalent factor in malnutrition in MHD is the uremic state. Contributors associated with uremia include inflammation and endocrine and metabolic alterations that induce catabolic
processes, inhibit anabolic processes, and influence
regulatory processes on appetite.
Inflammatory Process
A chronic inflammatory state with elevated levels
of tumor necrosis factor, interleukin-1, and interleukin-6 (IL-6) is associated with MHD patients; however, the cause of the inflammatory response is not
well elucidated.2 In cross-sectional studies, an elevated C-reactive protein (CRP) is present in 22% to
53% of MHD patients.1 A recent study investigated
association between serum albumin decline, acute
phase proteins, and nPCR.7 Of those patients who
showed significant decline in serum albumin levels
(21 of 59) over a 2-year period, there was also a
significant decrease in albumin synthesis, accompanied by significant increase in IL-6, CRP, 1AG, and
ceruloplasmin, which was not seen in the stable
group. Albumin synthesis and nPCR were unchanged in the stable group. A decrease of 0.3 g/dL
in serum albumin concentrations that persisted for 6
weeks was associated with a decrease in albumin
synthesis, with evidence of inflammatory response;
however, nPCR remained unchanged. The authors
concluded that inflammation is the primary cause of
a decrease in serum albumin concentration and
protein intake is insignificant.
Endocrine
Endocrine factors also negatively affect nutrition
status in MHD. There is a known increased resistance to anabolic hormones such as insulin, growth
hormone (GH), and insulin-like growth factor-1
(IGF-1). IGF-1 has been used to monitor nutritional
status as it is known to be sensitive to protein
intake. In addition to its use as a nutrition marker,
IGF-1 is believed to mediate the anabolic effects of
administered GH. Increased circulating levels of
IFG-1 seem to correlate with improved nitrogen
balance and reduction in blood urea nitrogen
response associated with short-term GH administration.8
Hyperparathyroidism or elevated parathyroid
hormone levels occur in 5%25% of MHD patients
and serve as a catabolic factor that enhances amino
acid release from muscles.9 Hyperparathyroidism is
also thought to affect appetite. A study of 15 MHD
patients status postparathyroidectomy resulted in
an observed progressive weight gain over the course
of 1 year.10
Hormone leptin levels are elevated in MHD
patients. This hormone is speculated to contribute to
decreased protein intake, loss of lean tissue and

203

body weight, and an increase in energy expenditure.9,1113

Chronic acidosis also contributes to malnutrition
by increasing protein degradation and inducing a
decrease in albumin synthesis.14,15 This is, in part,
associated with the suppressive effects of acidosis on
GH and IGF-1. A recent longitudinal observational
study was conducted with 248 MHD patients.16
Increasing delivered MHD bicarbonate dose was
associated with a significant inverse relationship
between nPCR and serum bicarbonate levels, leading the authors to conclude that increasing delivered
bicarbonate dose may decrease catabolism.
Altered amino acid profile in MHD patients is
similar to amino acid profiles of malnourished
patients where lower serum levels of branched chain
amino acids are thought to play a role in diminished
appetite.17 A recent hypothesis, called the tryptophan-serotonin hypothesis, has been postulated.
The altered amino acid profile in MHD, which
includes low concentrations of large neutral and
branched-chain amino acids with high tryptophan
levels, allows for a high rate of tryptophan transport
across the blood-brain barrier. High levels of tryptophan increase serotonin synthesis, which is a major
appetite inhibitor.18
Existence of poor appetite and low energy and
dietary protein intake has been reported in chronic
renal failure and in MHD patients. One of the
largest studies to date on dietary intake of MHD
patients included 1000 patients.19 The results of this
study found that the mean dietary energy intake of
MHD patients was 28 kcal/kg, and 60% of patients
had protein intakes of 1.0 g/kg. The majority had
protein and energy intake levels and nPCR levels
below National Kidney Foundation Kidney Disease
Outcome Quality Initiative (K/DOQI) guidelines. A
recent study involving 331 MHD patients found that
subjectively reported appetite of poor to fair
occurred in 38% of patients. Among other adverse
findings, a significant association between poor
appetite and increased rate of hospitalization and
mortality was determined.20

Calorie and Protein Needs of the

Hemodialysis Patient
K/DOQI published nutrition guidelines for clinicians to use as starting points for clinical decision
making. The guidelines are based on a structured
review of medical literature and the respected opinion of experts of a work group is included.14 There
are 26 guidelines addressing issues relevant to
nutrition care of the MHD and PD patient.
Per K/DOQI, protein needs for both stable and
acutely ill MHD patient are 1.2 g/kg/day, with 50%
recommended as high-biologic value.14 Caloric
needs for stable and acutely ill MHD patients are 35
kcal/kg/day for those under 65 years of age and 30 to
35 kcal/kg/day for those older than 65 years of age.14
According to K/DOQI, there are no published data

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available on energy requirements and limited data

on protein requirements of acutely ill MHD patients.
The guidelines acknowledge that although some
references show modest increase in resting energy
expenditure, MHD patients have decreased physical
activity, which will diminish energy needs. As for
protein requirements in acutely ill MDH patients,
protein intakes as high as 1.52.5 g/kg may be
required; however, no data prove that repletion of
protein stores is more effective by higher protein
provision than standard amounts.
Impact of the dialysis procedure itself on caloric
expenditure has been investigated and yields conflicting results. The more recent study included
MHD patients, PD patients, and chronic renal insufficiency patients (CRI).12 Energy expenditure was
determined by analysis of data from a whole-room
metabolic chamber. The authors found that the total
resting energy expenditure for patients requiring
HD or PD or with CRI was 41 kcal/kg, 42 kcal/kg,
and 33 kcal/kg, respectively. It is speculated that
perhaps the 20% increase in energy expenditure
may be reflecting the specific dynamic action of
food.12

Evaluation of Malnutrition in MHD

There is no single measurement to identify malnutrition in the MHD patient; therefore, it is suggested to use multiple parameters to evaluate for
malnutrition in MHD. As recognized by K/DOQI,
within the parameters there are complementary
and independent associations with morbidity and
mortality. However, a universal definition of mild,
moderate, or severe malnutrition has not resulted.
This poses difficulty in comparative interpretation of
clinical trials and studies and in defining optimal
intervention (nutrition support). The need for the
early identification of malnutrition and appropriate
intervention strategies is well appreciated by renal
clinicians. The parameters that have been used to
indicate malnutrition are reviewed elsewhere in this
publication and can be found in the K/DOQI guidelines as well.
In addition to well-recognized anthropometric
and laboratory parameters indicative of malnutrition, there are some parameters unique to the MHD
patient that increase suspicion of malnutrition. A
recent study of 68 MHD patients investigated the
relationship between interdialytic weight gain
(IDWG), malnutrition, and mortality risk.21
Patients were followed 24 months, having been
divided into 2 groups: group 1 (low IDWG) of 3%
dry weight/day, and group 2 with IDWG 3% dry
weight/day. Initial assessment of group 1 showed
that these patients had significantly lower predialysis levels of creatinine, prealbumin, and potassium
than patients in group 2. At the 24th month, the
same profile was evidenced, with the addition of
lower serum phosphorus concentrations, nPCR,
body weight, body mass index (BMI), and triceps

Vol. 20, No. 2

skinfold (TSF) in group 1. Further, over the course of

the study, 48% of patients in group 1 exhibited loss
of dry weight compared with 22% in group 2.
Patients in group 1 with low albumin levels had the
worst overall survival rate of 57.1%.

Intensive Diet Counseling Intervention for

Malnutrition in MHD
In the outpatient setting, maximizing nutrition
repletion efforts through intensive nutrition counseling and use of supplements are the most common
practical interventions. More aggressive modes of
nutrition intervention are more challenging and
difficult to initiate and manage in the outpatient
setting.
Maximizing nutrition repletion efforts through
intensive nutrition counseling is well illustrated in a
randomized, controlled study of 52 patients investigated for the impact of tailored intervention for
recognized barriers to adequate protein nutrition on
albumin levels.22 Barriers included poor knowledge
of protein-containing foods, poor appetite, needing
help with shopping or cooking, low fluid intake, and
inadequate dialysis. In this study, the dietitian
tailored the intervention to the determined barrier.
Patients who had a mean serum albumin level of
3.7 mg/dL bromcresol green or 3.4 mg/dL bromcresol purple for the previous 3 months were
included. Authors concluded that among intervention patients, 29% had a minimal change in albumin
(0.25 g/dL), 44% had moderate improvement
(0.25 0.49 g/dL), and 27% had a large improvement
(0.5 g/dL or greater). This contrasted with the control group receiving usual care, with results of 74%
with minimal change in albumin, 19% with moderate improvement, and 6% with large improvement.
Thirty-seven percent had multiple barriers, and
each barrier overcome was associated with improved
albumin levels. Of interest was that 56% and 68% of
patients at baseline were found to have clinically
significant elevations of CRP levels. Despite this,
among all patients with elevated CRP levels, 51%
showed minimal change in serum albumin concentrations, 32% had moderate improvement, and 17%
had large improvements at study end.

Nutrition Support Intervention

Large-scale randomized clinical trials of nutrition-support-mode interventions on morbidity and
mortality are lacking for all modes of nutrition
support interventions. Numerous problems include
study design, assessment parameters for malnutrition, length of study, number of patients treated,
and a variety of regimens and products used. These
problems are consistent among all nutrition-support
intervention modes studied and should be kept in
mind in the proceeding nutrition-support review
sections.

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PROVIDING NUTRITION SUPPORT IN OUTPATIENT DIALYSIS

Oral Supplements
The data on intervention in MHD patients using
oral supplements are surprisingly small. Most studies available evaluate the use of either standard or
renal supplements. Within these studies, sample
size is typically small, and average length of study is
312 months. Despite the limitations, the majority
of studies with use of supplement intervention in
malnourished MHD patients resulted in improved
indices of protein intake, biochemical, or anthropometric data.2325 Of interest are studies using specific types of amino acids or singular caloric modular. A randomized, double-blind study of 3 months
duration involved 29 MHD and 18 MPD patients.26
The treated groups received essential amino acid
(EAA) supplement of 720 mg daily. Patients were
stratified by serum albumin level: low albumin
level of 3.53.8 g/dL and very low albumin level of
3.5 g/dL. Compliance declined successively to 50%
compliance by study month 3 in both treated and
placebo groups. Results with respect to MHD group
treated with EAA showed a mean improvement of
0.2 g/dL in the very-low-albumin group vs 0.05 mean
serum albumin improvement in the low-albumin
group. There was a significant correlation between
baseline CRP levels and improvement in albumin.
There was no significant improvement in serum
transferrin, TTR, or anthropometrics in either
MHD-treated or placebo group.
A double-blind, crossover study involved 28
elderly malnourished MHD patients treated with
branched-chain amino acid (BCAA) supplements of
12 g/day for 6 months.27 Patients included in the
study were 70 years of age, with evidence of
malnutrition by a serum albumin concentration of
3.5 g/dL accompanied with anorexia. After 6
months supplementation with BCAA, anorexia and
poor intake improved, and albumin levels and
anthropometrics, which was not seen in the placebotreated group.
A prospective evaluation of glucose polymer supplement involved 22 MHD patients.28 Malnutrition
was assessed as moderately or severely malnourished by a score that included iron-binding capacity, serum albumin and cholesterol levels, BMI,
midbrachial circumference, arm muscle area, TSF,
and clinical impression. Patients received glucose
polymer in the amount of 100 g per day for 6 months.
Results were an increase in mean body weight of 2.4
kg, BMI, TSF, and brachial circumference; however,
nutritional status improved in only 4 of the 18 who
completed the study. Similar results of weight gain
were noted in another study using glucose polymer
supplement in 9 MHD patients, with follow-up
results of maintained weight.29
A recent intervention study evaluated the risk of
hospitalization and impact of varied oral supplements in patients at high risk of hospitalization.30
Patients were screened using the hemodialysis prognostic nutrition index (HD-PNI) to determine risk

205

for hospitalization. High-risk patients (HD-PNI

score of 0.8) received intervention with supplements daily for 3 months. The supplements varied
and were based on patient need determined by RD,
researcher, and physician and patient preference.
Before and after PNI, 24-hour recall and subjective
global assessment were assessed for risk of hospitalization, dietary intake, and nutritional status.
Authors concluded that 26 (22%) of the malnourished MHD patients were at increased risk of hospitalization, and those who received supplement
intervention decreased PNI scores; this equates to
decreased risk of hospitalization.
Of interest to usual practice is a study evaluating
the efficacy and cost-effectiveness of early standard
oral supplement intervention, which included 46
malnourished patients.31 Seventy percent of these
had evidence of mild malnutrition (serum albumin
levels of 3.53.7 mg/dL), and 30% evidenced moderate to severe range malnutrition (serum albumin
levels of 2.53.4 mg/dL). The mildly malnourished
group was separated into 2 groups: 1 group received
counsel only (A). The second group received counsel
and was provided with nutrition supplements (B).
The third group was the moderately to severely
malnourished patients (C). These patients received
counseling and either had supplements provided by
their insurance plans or had to purchase supplements. Supplements were prescribed in the amount
needed for patients to meet daily nutritional needs
according to an average of 2 24-hour recalls.
During the study period of 6 months, 57% of
patients in group A and 50% of patients in group B
achieved repletion of visceral protein stores, compared with only 7% achieving repletion in group C.
Group C required greater amounts of supplements
and also required more hospital days (208 days)
compared with group B (71 days) and group A (107
days). After a 3-month follow-up period, 14% of
patients in group A and 21% patients in group C
were able to maintain repletion (serum albumin
levels of 3.8 mg/dL for 2 consecutive months). In
group B, 61% had maintained repletion.
Patients are frequently financially responsible for
the purchase of supplements in the outpatient
hemodialysis setting. Given the small degree of
success in repleting and maintaining repletion in
moderately to severely malnourished MHD patients
with supplements as noted above, this route may be
suboptimal in repleting this subset of patients. In
addition to out-of-pocket expense for recommended
supplements, other contributing factors may include
noncompliance to dietary recommendations, palatability, and intolerance.32
Is the parenteral route more effective than the
oral route of supplementation in malnourished
MHD patients? Earlier studies with oral vs parenteral supplementation in MHD patients found significant advantage only with the parenteral route. A
more recent study in malnourished MHD patients
evaluated the use of oral EAA vs parenteral EAA in

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a group of 20 malnourished patients.33 Malnutrition

was defined by criteria of serum levels of albumin
4 g/dL, cholesterol 150 mg/dL, transferrin 200
mg/dL, and lymphocyte count 2000/mm3. In addition to a 60-g protein diet, half of the patients were
to be treated with 0.9 g/kg of oral EAA and the other
half were to receive 0.9 g/kg parenteral EAA.
Because of noncompliance stemming from unpalatable taste, nausea, and vomiting with oral preparations, 4 of 10 patients had to be transferred from the
oral to the parenteral group. At the completion of the
4-month study, statistical significance was found
with improved levels of serum albumin, creatinine,
and lymphocyte counts in the group receiving parenteral EAA. No improvement was seen in the group
receiving enteral EAA supplementation. Anthropometric measurements showed no change in either
group (BMI, percent body fat, triceps skinfolds,
midarm circumference, midarm muscle circumference). Authors concluded that the parenteral EAAs
were more effective and comfortable in the treatment of malnourished MHD patients.

Partial/Total Enteral Nutrition (TEN)

Data on TEN are very limited. The few available
references obtained show evidence of tolerance and
efficacy of TEN in MHD patients and improved
biochemical data but no change in weight.34,35
One recent study evaluating malnourished MHD
patients requiring partial or TEN support is a retrospective analysis performed on 10 patients.
Patients required partial or TEN to meet their
nutritional requirements. Six patients had percutaneous endoscopic gastrostomy (PEG) tubes, 3 had
nasogastric (NG) tubes, and 1 was switched from
PEG to NG because of exit-site infection. Four of the
patients required tube feeding 4 months, and 7
patients required tube feeding because of swallowing difficulties status post cerebral vascular accident. Results included significant improvement in
serum albumin from initial to final median albumin
levels: 2.8 mg/dL vs 3.4 mg/dL. Hypophosphatemia
was common, occurring in 8 of 10 patients. Authors
concluded that phosphorus levels should be monitored, and in specific cases, a nonrenal enteral
formula may be useful.

PN Intervention
Data on PN in the MHD patient is as limited as
with TEN. The few available references obtained
evidence tolerance and efficacy of these routes,
achievement of nitrogen balance, and improved biochemical data.36,37
The more recent study evaluated the relationship
between nitrogen intake and urea appearance in 5
acutely ill MHD patients. By results of 108 measurements in treatment courses, the average caloric
intake of (1984 55 kcal /d) and nitrogen intake
(11.0 0.8 g/d) resulted in positive nitrogen balance

Vol. 20, No. 2

(0.8 0.4 g/d) and a urea appearance rate of 9.4

0.8 g/d. To achieve nitrogen equilibrium required
28.3 kcal/kg ideal body weight (IBW) and 0.8 g
protein per kg IBW.
The use of PN as a route of alimentation in MHD
may limit or compromise future options for vascular
access sites, and the possibility of infection is of
concern because of the immunosuppressed state in
chronic renal failure.38

Intradialytic Parenteral Nutrition (IDPN)

Intervention
IDPN is a form of nutrition infused during the
hemodialysis procedure through the tubing of the
venous drip chamber. IDPN has been used empirically for over 2 decades. Initially it was believed that
an amino acid infusion given IV during HD would be
wasted into the dialysate bath. This was proven not
to be the case by work of Wolfson et al39 who showed
that two-thirds of amino acids infused were
retained. Some of the early investigation in use of
IDPN was directed toward observation of the impact
of correcting an abnormal amino acid profile associated with MHD patients.40 Sixteen patients with
10% body weight loss received infusion of 500 mL
8.5% general amino acid solution (GAA) with 500
mL 50% dextrose for 60 MHD sessions.41 Weight
gain at the rate of 0.18 pounds per treatment course
was observed with 8 of the 16 patients. Of interest is
that 8 of the 16 who did not respond with weight
gain displayed advanced metabolic bone disease.
Another group of 5 patients with 15% body weight
loss over the previous 6 months received EAA as 500
mL Nephramine (B. Braun Medical, Bethlehem, PA)
with 500 mL 50% dextrose. This group experienced
weight gain; however, their plasma aminograms
indicated a deficit of non-EAA. Further work by this
research group involved 18 patients infused with
IDPN consisting of 6.5% Renamin (Clintec, Deerfield, IL) with 250 mL 50% dextrose for 110 sessions.
Rate of weight gain was similar to solutions using
GAA.42
More recently, Foulks43 performed a medical evidence based review on IDPN. Numerous flaws in
studies included study design, limited follow-up,
lack of study details, nonuniform outcome criteria to
define malnutrition, and lack of reports on adequacy
of dialysis treatment. These flaws limit the usefulness of studies. Only 24 articles met criteria for
inclusion in the medical evidence based review, 3 of
which were randomized. Foulks43 indicated that
although the data supporting use of IDPN are weak,
the use of IDPN seems to be associated with
decreased mortality.
Two studies observed outcome criteria of
decreased morbidity and mortality. The first was a
study of 72 malnourished MHD patients receiving
IDPN over 2 years. Patients who responded to IDPN
(defined as those with a 0.5 g/dL increase in serum
albumin or total protein levels, or a 10% increase in

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PROVIDING NUTRITION SUPPORT IN OUTPATIENT DIALYSIS

weight) had lower mortality and decreased hospitalization compared with the nonresponders. The second study involved 81 malnourished MHD patients
treated over a 9-month period. Fifty-one were
treated with IDPN and 30 were treated with oral
supplements. Within the survivor group, IDPNtreated patients had significant weight gain,
whereas the nonIDPN-treated patients did not. (It
must be mentioned that survivors had a significantly higher weight at the start of the study than
the nonsurvivors.) In the nonsurvivor group, IDPNtreated patients lived longer than nonIDPNtreated (16.9 7.9 months), and treatment with
IDPN was related to survival.
Other compelling data are gleaned from a
12-month unblinded analysis of 1679 IDPN patients
and 22,517 non-IDPN controls. Results proved a
lower risk of death at 1 year in patients treated with
IDPN with serum albumin levels 3.5 mg/dL and
serum creatinine levels of 8.0 mg/dL. Over time,
these patients showed significant increases in levels
of albumin and creatinine not seen in nontreated
patients. An unusual finding was that those patients
treated with IDPN with normal albumin levels had
increased mortality.
Investigation as to the impact of IDPN with the
addition of recombinant human GH (rHuGH) is of
interest because this hormone promotes protein synthesis, decreases protein degradation, and enhances
lipolysis. The mediation of sequelae is thought in
part to occur via the hormone IGF-1. A small uncontrolled study of 7 malnourished MHD patients
addressed the use of IDPN with rHuGH. In this
study, malnutrition was defined as decline over the
previous 6 months to baseline serum albumin concentration of 3.2 mg/dL, transferrin 215 mg/dL,
and body weight 12.3% below IBW. The study consisted of a lead-in phase of a 1- to 2- week provision
of initiation and progression of IDPN to full
strength. Full-strength IDPN was then administered for 6 weeks, followed by IDPN with rHuGH for
6 weeks. The IDPN with rHuGH resulted in significant improvement in serum levels of albumin,
IGF-1, and transferrin. Because the IDPN phase
(without rHuGH) showed some improvement in
nutrition parameters, it is possible that continued
IDPN therapy might have resulted in further
improvement. Therefore, it remains inconclusive if
IDPN with rHUGH is superior to IDPN alone.
More recently, studies by Pupim et al44 have
provided evidence of significant positive effects of
IDPN on protein and energy metabolism by use of
isotopes. Seven patients were studied before, during,
and after IDPN during dialysis sessions with primed
infusion of leucine and phenylalanine. The patients
were well nourished, had no evidence of inflammatory process, had adequate dialysis, and acidosis had
been corrected. Results clearly showed that provision of calories and amino acids during hemodialysis
with IDPN reversed a net negative whole-body and
forearm muscle protein balance. Essentially, IDPN

207

changed a catabolic state to one of highly positive

protein balance. Whole-body protein synthesis
increased 2-fold during IDPN, and proteolysis was
50% lower. None of these beneficial effects carried
over to the postdialysis period. In a consequent
randomized crossover study of 6 well MHD patients,
this group found that exercise (15-minute period of
recumbent stationary bicycling, with workload set
at 40% maximal heart rate) combined with IDPN
promoted additive 2-fold increases in forearm muscle EAA uptake and net muscle protein accretion.45
Another randomized crossover study using isotopes
was performed on 7 well MHD by this group of
researchers, which proved that the administration
of IPDN improves the fractional synthetic rate of
albumin during MHD parallel with improvements
in whole-body protein synthesis.46 This research
group is currently investigating IDPN with isotopes
in malnourished hemodialysis patients.

Current Clinical Practice of IDPN

Patient Selection: Initiation and Termination of IDPN
A questionnaire completed by 143 renal clinicians
regarding use and practice of IDPN indicated a
significant need for better-defined IDPN guidelines
inclusive of current recommended practices in
patient selection, administration, monitoring, and
termination of IDPN. 47
Optimal patient selection criteria based on outcome are not yet clearly determined; however,
recent guidance for selection of patients and initiation and discontinuing criteria is available.14,38,48
First, K/DOQI guideline 19 (Table 1) illustrates
indications for nutrition support. Included in the
guidelines are 3 criteria posed to be met to determine the malnourished MHD patient who may benefit from IDPN. The criteria are (1) evidence of
protein or energy malnutrition and inadequate
dietary protein or energy intake; (2) evidence of the
inability to administer or tolerate adequate oral
nutrition inclusive of supplements and tube feeding;
and (3) those who by combination of oral or enteral
intake when combined with IDPN will meet the
individuals nutritional needs. The second source is
the NKF guidelines position paper entitled Proposed
Health Care Financing Administration Guidelines
for Reimbursement of Enteral and Parenteral Nutrition (Table 2). This article contains reference to
patient selection and nutrition intervention, with
progression to parenteral alimentation routes. The
third source provides recommendations in terms of
criteria for patient initiation and termination of
IDPN (Tables 3 and 4).
Substrate Considerations With IDPN
Optimal IDPN solution composition has not been
defined. Currently, published generally accepted
solutions are available.49,50 It is unknown if use of
these accepted formulas or tailored, individualized

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Table 1
K/DOQI Guidelines for Nutrition Support14
Indications for nutritional support
Individuals undergoing maintenance dialysis who are unable
to meet their protein and energy requirements with food
intake for an extended period of time should receive
nutritional support. (Evidence and Opinion)
The period of inadequate intake after which nutritional
support should be instituted ranges from days to 2
weeks, depending on the severity of the patients
clinical condition, degree of malnutrition (if any), and
the degree of inadequacy of their nutritional intake.
Before considering nutrition support, the patient should
receive a complete nutritional assessment.
Any potentially reversible or treatable condition or
medication that might interfere with appetite or cause
malnutrition should be eliminated or treated.
For nutrition support, the oral diet may be fortified with
energy and protein supplements.
If oral nutrition (including nutritional supplements) is
inadequate, tube feeding should be offered if medically
appropriate.
If tube feedings are not used, intradialytic parenteral
nutrition (IDPN; for hemodialysis) or intraperitoneal
amino acids (IPAA; for peritoneal dialysis) should be
considered if either approach in conjunction with
existing oral intake meets the protein and energy
requirements.
If the combination of oral intake and IDPN or IPAA
does not meet protein and energy requirements, daily
total or partial parenteral nutrition should be
considered.
The dialysis regimen should be regularly monitored and
modified to treat any intensification of the patients
uremic state that is caused by superimposed illness or
increased protein intake.
K/DOQI, Kidney Disease Outcome Quality Initiative.
Reprinted from National Kidney Foundation. K/DOQI Clinical
Practice Guidelines for Nutrition in Chronic Renal Failure. Am J
Kidney Dis. 2000;35(suppl 2):81140, with permission from the
National Kidney Foundation.

solutions according to maximal substrate use rates

is more efficacious in the repletion of the malnourished MHD patient. Clinician understanding of substrate utilization and efficient utilization rates is
imperative for safe and effective IDPN provision.
Glucose clearance and oxidation vary, with maximal clearance ranging from 39 mg/kg/min having
been reported.51 The potential for insulin resistance,
hyperglycemia, or hypoglycemia exists.
Impact of amino acid provision in IDPN results in
an increased urea volume and decrease in Kt/V, the
latter of which is a measure of dialysis adequacy.
Kt/V and URR should be monitored and dialysis
prescription change addressed as indicated.52 Protein provision also necessitates attention to and
correction of low serum bicarbonate levels as low
serum bicarbonate levels have deleterious effects
on amino acids and albumin synthesis as described
earlier.
Abnormal lipid profile is associated with chronic
renal disease. In a study of 240 MHD patients, blood

Vol. 20, No. 2

analysis of lipid parameters (after 14-hour overnight

fast) revealed that MHD patients had significantly
higher triglyceride (TG) and lower high density
lipoproteins and Apo-1 levels compared with controls.53 Serum carnitine deficiency is found in MHD
patients, and elevated TG levels may warrant investigation of serum carnitine level. The use of IV
carnitine currently is controversial.54 Knowledge of
these abnormalities may warrant concern in use of
IV fat emulsion in IDPN regimens. In an early study
of 26 malnourished MHD patients, use of IV fat
emulsions at 1.6 g/kg (equivalent to 6.7 mg/kg/min),
along with amino acids, was deemed to be safe and
effective with respect to TG, cholesterol, apolipoprotein-B, and phospholipid levels.55
In contrast, concern has been raised as to safety
in the use of IV fat emulsion in MHD patients.
Halberg56 assessed maximal clearance rate of IV fat
emulsion to be 2.67 mg/min for a normal adult.
Infusion of IV fat emulsion at 5.2 mg/kg/min
resulted in decrease in cardiac output and increase
in capillary wedge pressure in postoperative coronary bypass patients. These effects were not seen

Table 2
NKF Proposed Guidelines for Nutrition Support38
1. The criteria used to diagnose malnutrition in the nonrenal
patient are inappropriate for the MHD patient. It is
hazardous to the dialysis patient to allow the serum
albumin concentration or body weight to decrease to the
proposed values before instituting nutritional therapy. The
following changes in nutritional criteria are proposed for
instituting nutritional therapy in the maintenance dialysis
patient who has documented low nutrient intake:
Serum albumin level 3.4 g/dL
Actual body weight 90% of ideal body weight
Documented protein intake 0.8 g/kg/d
2. There must be documentation of efforts to correct
underlying medical, psychiatric, psychosocial, and
surgical disorders that may impair food intake to increase
voluntary oral intake of nutrients in malnourished dialysis
patients.
3. For the small subset of dialysis patients who do not
respond to medical, surgical, or psychiatric therapy,
nutritional counseling, and the prescription of food
supplements, a trial of tube feeding may be indicated.
4. For maintenance dialysis patients who have
contraindications to or side effects from tube feeding,
daily IV nutrition and IDPN are considered therapeutic
options.
5. Tube feedings, daily IV nutrition, and IDPN should be
reimbursed at rates appropriate to the costs of the
specific treatment administered to the patient.
6. The use of IDPN should be monitored carefully, and
acceptance for reimbursement should be made on a
case-by-case basis.
NKF, National Kidney Foundation.
Reprinted from Kopple J, Foulks C, Piraino B, Beto J, Goldstein J.
National Kidney Foundation position paper proposed Health Care
Financing Administration guidelines for reimbursement of enteral
and parenteral nutrition. Am J Kidney Dis. 1995;26:995997, with
permission from the National Kidney Foundation.

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PROVIDING NUTRITION SUPPORT IN OUTPATIENT DIALYSIS

Table 3
Criteria for initiating IDPN48
1. 3-Month rolling average predialysis serum albumin level
3.4 g/dL
2. 3-Month rolling average predialysis serum creatinine level
8.0 mg/dL
3. Weight loss 10% of ideal body weight or 20% of usual
body weight (no time constraint)
4. Clinical examination compatible with moderate to severe
malnutrition
5. Dietary history of decreased intake
Protein 0.8 g/kg
Calories 25 kcal/kg
6. Subjective global assessment: C rating (severe
malnutrition)
Any 3 of the above with
Failed attempts at increased dietary and oral supplemental
therapy
Refusal to undergo enteral tube feeding
Reprinted from Lazarus J. Recommended criteria for initiating and
discontinuing intradialytic parenteral nutrition therapy. Am J Kidney
Dis. 1999;33:211216, with permission from the National Kidney
Foundation.

when IV fat emulsion was infused at 2.67 mg/kg in a

similar group of patients. Fat emulsion administration 4.0 mg/kg/min exceeds ability for clearance.57
The administration of an IV fat tolerance test inclusive of 17 controls, 25 patients with CRI, and 32
patients receiving MHD showed decreased fractional removal rate of IV lipid in the CRI and MHD
patients that was inversely related to serum TG
and fasting blood glucose levels compared with
controls.58
Another concern with IV fat emulsion provision is
the potential for toxicity of free fatty acids (FFA).
Because FFA are bound to albumin, patients with
low albumin levels may have elevated levels of FFA.
Toxicity of FFA includes cardiac dysfunction,
arrythmias, and pulmonary injury.59
Rapid infusion or infusion in seriously ill patients
results in particles taken up by the reticuloendothelial system, and continued fat loading has potential
for impact on immune function. There is also evidence that rapid infusion can provoke prostaglandin-mediated pulmonary vasoconstriction and
hypoxemia.60 Consideration of clearance capacity of
IV fat emulsion in provision of IDPN to malnourished patients is prudent in patients of low body
weight and those with pulmonary compromise.
Administration and Monitoring of IDPN
Infusion providers for IDPN may provide administration and monitoring guidelines. A comprehensive set of IDPN guidelines inclusive of tailored
solutions, administration, biochemical and physical
monitoring, and solution composition was presented
at the Renal Section meeting of the American Society of Parenteral and Enteral Nutrition (A.S.P.E.N.)
in 2002. The guidelines are available through the

209

chairman of the A.S.P.E.N. Renal Section (contact

aspen@nutr.org).
Effective administration and monitoring of IDPN
in the dialysis unit setting requires additional time,
work, and effort of the part of the physician, nurse,
pharmacist, and dietitian, who may not be well
versed in nutrition support. There is a necessary
investment of time in education and training of unit
clinicians, inclusive of training on proper handling
and storage procedures, IDPN bag and solution
inspection for evidence of particulate matter or separation, use of the infusion pump, and administrative procedures with vitamins and medications.
Further, unit clinicians must be familiar with
signs and symptoms of physical intolerance to IDPN
in order to implement appropriate corrective measures. Physical signs and symptoms of intolerance
may be related to temperature of administered solution, volume or substrate intolerance, electrolyte
imbalance, or nutrient deficiencies. Clinicians need
education on the necessity for glucose monitoring
and insulin-regimen management. Fluid management is based on sound nursing assessment for
appropriate fluid-removal determination. The nutrition professional should be knowledgeable in substrate provision considerations and clinical manifestations of vitamin, mineral, and nutrient deficiency
states and should individualize provision.
An understanding and anticipation of metabolic
consequences of the refeeding syndrome is necessary, with monitoring and provision of additional
electrolytes, magnesium, and phosphorus. Corrective measures of these deficits should include careful
consideration regarding changes in dialysate bath,
oral medications, or by addition of salts to IDPN.
Time investment is considerable but necessary to
provide for safe and effective management of IDPN.
The IDPN patient should be closely monitored and
receive ongoing physical and nutrition assessment
inclusive of biochemical laboratory parameters,
anthropometrics, and dialysis adequacy parameters.
Table 4
Criteria for discontinuing IDPN48
1. Attaining a 3-month rolling average predialysis serum
albumin level of 3.8 g/dL
2. Attaining a 3-month rolling average serum creatinine
level of 10 mg/dL
3. Clinical examination of improving nutrition, including
increased dry weight
4. Subjective global assessment: A or B rating
5. Increase in oral intake to
Protein intake 1 g/kg
Calorie intake 30 kcal/kg
Any 3 of the above or either
No improvement after 6 months of IDPN therapy
Complications or intolerance of IDPN therapy
Reprinted from Lazarus J. Recommended criteria for initiating and
discontinuing intradialytic parenteral nutrition therapy. Am J Kidney
Dis. 1999;33:211216, with permission from the National Kidney
Foundation.

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MOORE AND CELANO

Reimbursement Issues With IDPN: History,

Controversy, and Current Status
In 1972, Medicare created the ESRD Program.
Suddenly, Medicare provided unfortunate individuals with kidney failure the ability to continue living
with access to dialysis as a covered benefit. Before
the ESRD program, a local community board determined which ESRD patients would have access to
dialysis therapy. Dialysis therapy was limited in
availability, and the difficult decisions on which
patients would be provided dialysis were often
focused on an individuals redeeming value to society. When Medicare established the ESRD program,
it projected providing dialysis to approximately
25,000 patients throughout the United States. That
projection was shattered, and today there are over
350,000 ESRD patients receiving dialysis, with the
alarming growth rate of approximately 8% per year.
In the 1980s, IDPN emerged as a controversial
nutrition therapy; however, it ultimately gained
status as a Medicare-covered benefit. During this
time period, IDPN came in and out of Medicares
graces as a covered benefit. As controversy over the
effectiveness of IDPN escalated, providers and
Medicare engaged in ongoing discussions that
focused on the efficacy of IDPN, along with studies
and supporting evidence on the advantages of early
intervention with IDPN. In the end, IDPN became a
recognized covered benefit by Medicare and over
time demonstrated itself to be an efficacious intervention for the nutritionally depleted dialysis
patient with malnutrition secondary to malabsorption. Providers and their clinical staff followed the
lead and committed efforts of Dr Edward Lowrie of
National Medical Care (NMC) and continued to
compile supporting studies and documentation on
the overall benefits and effectiveness of IDPN intervention. Throughout the 1990s, IDPN grew as the
intervention of choice for the MHD patient with
malnutrition associated with malabsorption.
In 1994, HCFA implemented a change of Medicares structure and created 4 regional carriers
called Durable Medical Equipment Regional Carriers. At this time, coverage criteria for PN and IDPN
tightened and enteral feeding criteria loosened.
IDPN, however, came under considerable scrutiny
by Medicare as a covered benefit.
The HCFA/Medicare decision was to terminate
virtually all reimbursement for IDPN. This occurred
without notice to the providers and included existing
patients receiving IDPN therapy with claims
already being paid by Medicare. These actions by
HCFA/Medicare precipitated confrontation between
the IDPN providers and the government. Medicare
appeals, hearings, and legal discussions continued
throughout the following year. Evidence in support
of IDPN was presented during the hearings; however, the government did not veer from its new
position specific to IDPN. Ultimately, the providers
abandoned their efforts.

Vol. 20, No. 2

The IDPN industry alerted the government to the

consequences of eliminating IDPN as a Medicare
benefit provided during outpatient dialysis. It predicted that the new Medicare requirements for
IDPN coverage would increase the number of
patients hospitalized for severe decline in nutritional status and resulting secondary complications.
More frequent hospitalizations or longer hospitalizations may result in additional hospitalization
costs.
IDPN therapy currently is covered for a hospitalized patient under Part A Medicare (inpatient hospitalization coverage); however, IDPN therapy in
the outpatient setting must meet criteria as a covered benefit under Medicare Part B. The Medicare
Part B policy for IDPN requires the following: (1) a
true gastrointestinal (GI) diagnosis as evidenced in
the medical records, with supporting documentation; (2) test results that conclusively prove that
malabsorption exists (eg, quantitative fecal fat tests
or invasive GI testing); (3) a required enteral tube
feeding attempt and failure, unless severe clinical
contraindication exists and is well documented; (4)
physical wasting and documented weight loss below
ideal body weight; (5) abnormally low serum albumin levels and other nutritional indicators; and (6)
demonstration that all possible interventions have
been attempted, exhausted, and failed before considering IDPN as the last resort (eg, medication intervention and proof of its failure or an enteral tube
feeding attempt and failure). For an outpatient
MHD patient who exhibits considerable nutrition
risk, early intervention with IDPN is elusive
because of the strict criteria.
Although IDPN remains a covered benefit provided by Medicare, claims have been denied for
payment even when these strict medical criteria are
met. In the last year, 3 IDPN patients in different
parts of the country who met Medicares coverage
criteria were observed and tracked. IDPN was provided to these patients and Medicare denied payments for claims to the provider. After 3 levels of
appeals for payment on these denied claims, an
administrative law judge (ALJ) ruled that the
claims should be paid. The ALJ based the decision
on testimony by its own government expert witness,
a gastroenterologist. In all 3 cases, the physician
determined that the patient needed IDPN to sustain
life, that the patient met Medicares criteria for
IDPN coverage, and that the claimed amounts by
the provider were to be paid. These conclusions were
reached 1 year after the initial date of providing
IDPN therapy and the subsequent claims processing.
The evolution of dialysis and its tremendous
growth, the economic ramifications of Social Security/Medicare with the enlisting infant boomers, and
the increase in life expectancy (78 years and increasing at 3 months per year) may all have helped
precipitate Medicares scrutiny of IDPN. It is possible that on review of expenditures already being

April 2005

PROVIDING NUTRITION SUPPORT IN OUTPATIENT DIALYSIS

provided within the ESRD program, the government

recognized it would have considerable difficulty in
the ability to continue providing other life-supporting services beyond dialysis therapy.

Conclusion
There are several challenges to providing nutrition support to patients in outpatient hemodialysis
settings. There is significant economic challenge in
obtaining coverage for nutrition-support interventions. In consideration of the extent of malnutrition
in the growing MHD population, outcome research
is needed to examine economic utility (cost:benefit
ratio) for optimal intervention with various modes of
enteral and PN support. Universal definition of
mild, moderate, and severe malnutrition in MHD
would allow for comparative interpretation of the
results of such research. This research is particularly necessary with IDPN to control for its appropriate use and to help render change in Medicare
reimbursement. A subset of malnourished MHD
patients exists for whom intense dietary counseling,
oral nutrition supplements, or tube feeding are ineffective in improving nutritional status. The ability
to provide IDPN to those patients is ethical and
necessary. Investigation and clarification to this end
requires collaborative efforts of ESRD networks;
supportive members of A.S.P.E.N., Counsel on
Renal Nutrition (CRN), and American Nephrology
Nurses Association; nephrologists; researchers; and
therapy providers.
Another challenge is understanding the complexity of uremic malnutrition inclusive of inflammation
and endocrine and metabolic alterations. Research
is needed to determine effective anticatabolic and
anabolic strategies.
Specific to clinical practice is the challenge of
enhancing clinicians skill with IDPN. Bridging the
gap of nutrition-support expertise required for IDPN
provision by unit clinicians has been identified.
Education and training of unit clinicians by those
experienced with IDPN are necessary for safe and
effective therapy provision within current acceptable practice of PN support.
Early detection of malnutrition in MHD inclusive
of intensive dietary counseling, individualized nutrition care plans, and the application of knowledge of
effective nutrition support interventions constitutes
best practice.

Acknowledgments
The authors thank Kristin Roach RD, LD, of
DaVita Dialysis for assistance with this manuscript.
Zebbie Nix, RD, LD, and Teresa Edmunds, RN, of
INTRX HealthCare (New Orleans) who contributed
to the Reimbursement Issues with IDPN segment
of this article.

211

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