Nephrol Dial Transplant (2001) 16: 1856±1862
Original Article
Oral supplementation of branched-chain amino acid improves
nutritional status in elderly patients on chronic haemodialysis
Kinya Hiroshige, Toshiyo Sonta, Takeshi Suda, Kaori Kanegae and Akira Ohtani
Renal Division, Social Insurance Chikuho Hospital, Fukuoka, Japan
Abstract
Background. Anorexia may be associated with
decreased plasma levels of branched-chain amino
acids (BCAA). In malnourished elderly haemodia-
lysis (HD) patients, oral BCAA supplementation may
improve anorexia, resulting in improved nutritional
status.
Methods. Among 44 elderly (age )70 years) patients
on chronic HD, 28 patients with low plasma albumin
concentration (-3.5 gudl) were classi®ed as the mal-
nourished group; they also suffered from anorexia.
The other 16 patients did not complain of anorexia and
were classi®ed as the well-nourished group. We per-
formed a 12-month, placebo-controlled, double-blind
study on the malnourished group. Fourteen patients
each received daily oral BCAA supplementation
(12 guday) or a placebo in random order in a crossover
trial for 6 months. Body fat percentage, lean body
mass, plasma albumin concentration, dietary protein
and caloric intakes, and plasma amino acid pro®les
were monitored.
Results. Lower plasma levels of BCAA and lower
protein and caloric intakes were found in the mal-
nourished group as compared to the well-nourished
group. In BCAA-treated malnourished patients, anor-
exia and poor oral protein and caloric intakes improved
within a month concomitant with the improvement in
plasma BCAA levels over the values in well-nourished
patients. After 6 months of BCAA supplementation,
anthropometric indices showed a statistically signi®cant
increase and mean plasma albumin concentration
increased from 3.31 gudl to 3.93 gudl. After exchanging
BCAA for a placebo, spontaneous oral food intake
decreased, but the favourable nutritional status per-
sisted for the next 6 months. In 14 patients initially
treated with a placebo, no signi®cant changes in
nutritional parameters were observed during the ®rst
6 months. However, positive results were obtained
by BCAA supplementation during the subsequent
Correspondence and offprint requests to: Kinya Hiroshige MD, Renal
Division, Social Insurance Chikuho Hospital, 765-1 Yamabe,
Nougata City, 822-0034 Fukuoka, Japan.
# 2001 European Renal Association±European Dialysis and Transplant Association
6 months, and mean plasma albumin concentration
increased from 3.27 gudl to 3.81 gudl.
Conclusions. Normalization of low plasma levels of
BCAA by oral supplementation can reduce anorexia
and signi®cantly improve overall nutritional status in
elderly malnourished HD patients.
Keywords: branched-chain amino acids; dietary intake;
elderly patient; haemodialysis; nutrition
Introduction
Malnutrition, which is frequently encountered in
elderly patients on chronic haemodialysis (CHD), is
multifactorial in origin, the contributing causes includ-
ing ageing itself w1±3x. It is also generally accepted
that nutritional status depends on the dialysis dose
delivered, and low dialysis ef®cacy is associated with
higher rates of morbidity and mortality. Anorexia is
likely to be a causative factor of malnutrition, espe-
cially in elderly patients. Previous studies indicate
a possible relationship between plasma levels of
branched-chain amino acids (BCAA) and appetite
w4±6x. With or without dialysis, the plasma amino-
acid pro®le in renal failure patients exhibits abnormal
patterns, such as reduced essentialunon-essential amino
acids and lower BCAA level w7±9x. Therefore in
anorectic CHD patients who do not respond to con-
ventional therapies for malnutrition, such as nutritional
counselling and diet modi®cation, oral or parenteral
BCAA supplementation may be warranted.
In the general population receiving CHD, a few
studies have shown no signi®cant bene®t of oral essen-
tial amino acid supplementation w10,11x. However,
in many studies at least some bene®t of intradialysis
parenteral nutrition containing multiple amino acids
was documented to improve visceral protein synthesis,
anthropometric measures, and immunocompetence,
although these studies could not demonstrate the nor-
malization of impaired plasma amino-acid pro®le and
did not refer to changes in appetite w12±15x.
Branded-chain amino acids supply in elderly HD patients
In previous studies the amount of BCAA admin-
istered orally or parenterally was relatively small
(30±50 guweek) because of the use of multiple amino-
acid solutions. To clarify the relationship between
BCAA and appetite, researchers must normalize the
plasma BCAA level by administering relatively large
amounts of only BCAA. In general, BCAA granules
are used for the treatment for hepatic encephalopathy.
Also, numerous controlled trials have used BCAA as
a nutritional therapy in patients with chronic liver
disease w16x. To our knowledge, there are no other
reports concerning the exclusive use of BCAA granules
as the strategy for treating malnutrition in dialysis
patients. Little investigative effort has been given
to studying the nutritional status and treating mal-
nutrition in elderly CHD patients. In this study, we
chose the simple method of oral supplementation with
commercially available BCAA granules (84 guweek) in
elderly CHD patients with anorexia and investigated
the effect on spontaneous oral food intake and overall
nutritional status.
Subjects and methods
Patients population
Fifty-nine patients over 70 years of age undergoing CHD in
our unit were assessed for inclusion in this study. Strict
inclusion criteria were used: we excluded patients with
malnutrition factors unrelated to dialysis. Eight patients
with severe complications affecting exercise capacity, such
as old cerebral infarction or myocardial infarction, were
excluded. Five patients with evidence of underlying disease,
such as collagen disease, liver cirrhosis, malignancy, psy-
chological disorders, or endocrinological disorders, were
also excluded. Diabetic patients were included, but none
received exogenous insulin administration. Two patients
who had continuous elevation of carboxyl-terminal para-
thyroid hormone (c-PTH; )20 nguml) were also excluded.
Thus 15 patients were excluded for one or more of the
reasons mentioned above, and the remaining 44 patients
were included in the study. All subjects were outpatients and
not employees. Written informed consent from patients was
obtained, and the study was conducted in accordance with
the principles of the Declaration of Helsinki of the World
Medical Association.
All patients were maintained on thrice-weekly CHD treat-
ment using bicarbonate as the buffer solution for appro-
priately 4 h at a time. The haemodialyser used during the
experimental period was polysulphone (PS; Fresenius, Bad
Homburg, Germany), which was sterilized by autoclave.
The haemodialysers were not reused. All patients were stable,
and none had recently undergone surgery. None had signi®c-
ant daily diuresis, which was con®rmed by 48-h urine
collection of a volume less than 50 ml during the baseline
period.
Study design
This study was a 12-month randomized, placebo-controlled,
double-blind, crossover trial with a 3-month baseline period
prior to the study.
1857
Baseline period
Counselling by a certi®ed dietician was performed monthly
for all patients, and the following renal diet was pre-
scribed. The recommended energy intake was 35 kcalukg
body weightuday and that for protein was 1.2 gukg body
weightuday. Nutritional evaluation was performed at the start
and the end of the baseline period. Despite the intensive diet
counselling, 28 patients with depressed serum albumin
(-3.5 gudl) at the end of the baseline period were classi®ed
into the malnourished group; they complained of anorexia
to various degrees during the baseline period. Sixteen
patients with a normal range of serum albumin ()3.6 gudl)
were classi®ed into the well-nourished group; they did not
complain of anorexia. We also studied healthy age- and
sex-matched elderly persons for the measurement of nutri-
tional parameters. Plasma amino acid pro®les and other
biochemical measures such as lipid pro®le, magnesium, zinc,
and c-PTH in plasma were determined at the end of the
baseline period in all patients, including the healthy control
subjects. C-reactive protein in plasma and bicarbonate
concentration in arterial blood were also measured.
Study period
The 28 malnourished patients were randomly assigned to
receive either placebo (group 0) or BCAA supplementation
(group 1) for the ®rst 6 months and then the opposite
treatment for the next 6 months. Three times daily, patients
received BCAA granules orally (Livact1, Ajinomoto Co.
Ltd, Tokyo, Japan), which consisted of valine (1.1 g), leucine
(1.9 g), and isoleucine (1.0 g), at a total dose of 12 guday.
All patients received 4 g BCAA mixed with 2 g dextrose
at a time. The placebo containing 6 g dextrose was ident-
ical in appearance and taste. Compliance with treatment
was evaluated monthly. All patients consumed the BCAA
granules exceeding 90% of the prescribed dosage. Sixteen
well-nourished CHD patients (group 2) received no nutri-
tional supplementation during the study period. Group
demographic characteristics are shown in Table 1. No
signi®cant differences in age, gender, haemodialysis dura-
tion, or underlying disease were observed among the three
groups.
Nutritional surveys including plasma amino acid pro®les
were performed at 1, 3, 6, 7, 9, and 12 months after the
start of this study for groups 0 and 1. During the study
period, including the baseline period, anaemic status was
Table 1. Demographic characteristics of patients
Group 0 Group 1 Group 2 Healthy
subjects
Number 14 14 16 20
Age (years) 74"8 75"7 73"6 74"8
Sex (male : female) 7:7 6:8 8:8 8 : 12
Dialysis duration (years) 6.8"3.4 6.9"3.1 6.4"3.3 ±
Underlying disease
DN 6 5 8 ±
CGN 6 6 6 ±
BNS 2 3 2 ±
In all parameters, no signi®cant differences among groups 0, 1, and 2
were observed. Age and dialysis duration values are means"SD.
DN, diabetic nephropathy; CGN, chronic glomerulonephritis; BNS,
benign nephrosclerosis.
1858
appropriately treated with recombinant human erythro-
poietin, and the mean haematocrit level in each group
ranged from 25 to 30% during the study period. Dialysis
ef®cacy manifested by KtuV urea was determined every
2 weeks and was maintained at near 1.4, mainly by changing
the blood ¯ow rate.
Nutritional survey
Nutritional status was evaluated using plasma albumin
concentration, dietary nutrient intake, and anthropometric
measures such as body-fat percentage and lean body mass.
Dietary protein and caloric intakes were estimated from diet
records for 7 consecutive days by a certi®ed dietician. To
determine each patient's actual KtuV urea, we used the urea
kinetic modelling formula developed by Daugirdas w17x.
Plasma was obtained just before the ®rst dialysis session
in a week for the measurements of albumin, amino acid
pro®le, and other biochemical measures.
Height was measured and dry body weight was determined
monthly by clinical manifestation and chest X-ray and
ultrasonographic readings of the inferior vena cava. Total
fat percentage (%) and lean body mass (kg) were deter-
mined using bioelectrical impedance analysis in a standard
fashion using a four-electrode, single-frequency (50 kHz)
impedance plethysmograph (model TBF-410, Tanita Co.
Ltd., Tokyo, Japan). All anthropometric measurements
were taken after the last dialysis session in a week to
minimize any distortion caused by excess tissue ¯uid.
Laboratory investigation
Blood urea, plasma albumin concentration, and plasma lipid
pro®le were determined by routine methods. Plasma con-
centrations of zinc were determined by the atomic absorbing
method, magnesium by the ultraviolet absorbing method
using xylidyl blue, and c-PTH by radioimmunoassay.
Plasma was deproteinized quickly for amino acid analysis
by adding 45 mg sulphosalicylic aciduml plasma, and the
precipitate was removed by centrifugation. The supernatant
was quickly frozen at 308C until analysed. Amino acids
were measured with a Beckman 121M amino acid analyser
(Beckman Instruments, Palo Alto, CA) using a lithium
buffer system.
Statistical analysis
All data are expressed as means"standard deviation (SD),
unless otherwise indicated. A two-way analysis of variance
was used to compare means between groups. Within-group
comparisons were made with the Wilcoxon rank-sum test
or with a paired Student t-test, as appropriate. A comparison
of discrete variables in different groups was performed using
a Fisher exact test. Differences were considered signi®cant
when a two-sided P value was -0.05.
Results
Baseline nutritional status
During the baseline period, in the 28 anorectic,
malnourished patients no signi®cant alterations in
nutritional indices were observed, despite intensive
K. Hiroshige et al.
diet counselling (Figure 1). Therefore, values obtained
at the end of the 3-month baseline period (month 0)
were taken as baseline values (Table 2). As noted,
malnourished patients (groups 0 and 1) had a signi-
®cantly lower mean plasma albumin concentration
(3.27"0.22 and 3.31"0.21 gudl respectively) than well-
nourished patients (group 2; mean 3.93"0.26 gudl).
Dry body weight, body-fat ratio, and dietary protein
and caloric intakes were signi®cantly lower in groups 0
and 1 than in group 2 (P-0.01). Despite adequate
dialysis in these groups, with mean KtuV urea over
1.4, all patients in groups 0 and 1 complained of
anorexia possibly causing poor food intake, which
led to a nutritionally depleted state. There were no
signi®cant differences in arterial bicarbonate concen-
tration and plasma concentrations of total cholesterol,
triglyceride, magnesium, zinc, c-PTH, and C-reactive
protein among the 3 groups. Plasma BCAA levels were
signi®cantly lower in groups 0 and 1 than in group 2
(Table 3). Healthy subjects were better nourished
than patients in group 2 and had signi®cantly higher
plasma albumin and BCAA levels (Tables 2 and 3).
Effect of BCAA supplementation on
amino acid pro®les
The changes in plasma BCAA levels over time are
shown in Figure 2. In group 1, after the adminis-
tration of BCAA granules, rapid increases in plasma
BCAA levels were observed within a month, and
this favourable change persisted throughout the
®rst 6 months of this study. The same observation
was made on group 0 patients, who received BCAA
supplements from 6 months after the start of this
study, whereas the placebo did not have any in¯uence
on BCAA levels during the initial 6-month period.
Peak plasma BCAA levels in both groups 0 and 1
became higher than basal values in healthy subjects
(Table 3). Patients in group 1 showed a rapid decline
in plasma BCAA levels after substituting the placebo
for BCAA granules; those levels returned to near
the baseline values within 3 months. Essential and
non-essential amino acids, except BCAA, were not
signi®cantly altered by BCAA supplementation during
the study period.
Effect of BCAA supplementation on
nutritional parameters
The time course of nutritional parameters, including
oral food intake, are shown in Figure 1. All patients
in group 1 had a rapidly improved appetite, which
resulted in a rapid increase of dietary protein and
caloric intakes in parallel with the increase in plasma
BCAA levels. These favourable responses persisted
throughout the BCAA supplementation period.
The mean plasma albumin concentration of 3.31 gudl
at the start signi®cantly improved after 3 months
and increased to 3.93 gudl, which is exactly that in
well-nourished patients (group 2; mean 3.93 gudl).
Anthropometric measurements also signi®cantly
Branded-chain amino acids supply in elderly HD patients 1859

Fig. 1. Longitudinal changes in various nutritional parameters in elderly haemodialysis patients with anorexia. In groups 0 and 1, rapid
increases in oral protein and caloric intakes after the administration of branched-chain amino acid (BCAA, arrow) granules were followed by
increases in serum albumin concentration and anthropometric indices. Closed circles, group 0; open circles, group 1. *P-0.05, **P-0.01
compared to the basal values; yP-0.05, yyP-0.01 compared to the values at 6 months.

Table 2. Baseline nutritional parameters

Group 0 Group 1 Group 2 Healthy subjects

Dry body weight (kg) 40.9"6.4** 42.9"7.5* 48.6"7.2 52.1"7.3

Body mass index 17.8"1.9** 19.0"2.1* 20.3"2.4 22.6"2.3
Body fat percentage (%) 12.8"4.3** 14.1"4.5** 17.3"3.6 19.2"5.3
Lean body mass (kg) 35.6"4.3** 36.9"3.9* 40.2"6.8 42.1"6.5
DPI (gukg BWuday) 1.03"0.14** 0.98"0.10** 1.16"0.17 1.15"0.15
DCI (gukg BWuday) 25.9"3.6** 26.6"3.1** 30.2"3.9 35.2"5.1
Plasma biochemical measures
Albumin (gudl) 3.27"0.22** 3.31"0.21** 3.93"0.26 4.16"0.38
Total cholesterol (mgudl) 154"34 151"30 168"47 178"41
Triglycerides (mgudl) 68"27 76"31 88"36 104"37
Zinc (mmolul) 68"15 73"20 74"29 124"31
Magnesium (mmolul) 2.8"0.7 2.7"0.9 2.9"0.8 1.9"0.5
C-PTH (nguml) 5.2"1.8 6.0"3.4 6.4"5.4 0.6"0.3
C-reactive protein (mgudl) 0.3"0.4 0.2"0.5 0.3"0.4 0.2"0.4
Arterial bicarbonate (mEqul) 18.5"3.1 17.9"4.5 18.9"5.2 ±
KtuVurea 1.41"0.12 1.42"0.10 1.43"0.14 ±

DPI, dietary protein intake; DCI, dietary caloric intake; C-PTH, carboxyl-terminal parathyroid hormone. All values are means"SD.
*P-0.05, **P-0.01 compared to the results in group 2.

Table 3. Baseline branched-chain amino acid (BCAA) pro®le

Group 0 Group 1 Group 2 Healthy subjects

Valine (mmolul) 142.5"26.4** 148.3"36.6** 174.0"36.0 226.1"48.3

Leucine (mmolul) 68.4"15.2** 64.4"23.9** 88.2"26.1 124.3"35.9
Isoleucine (mmolul) 49.0"7.6* 47.0"11.5* 56.8"12.1 71.9"19.3
BCAAutotal amino acids 0.087"0.019* 0.088"0.022* 0.121"0.034 0.172"0.042

All values are means"SD. *P-0.05, **P-0.01 compared to the results in group 2.
1860 K. Hiroshige et al.

Fig. 2. Longitudinal changes in plasma amino-acid pro®les in elderly haemodialysis patients. Branched-chain amino acid (BCAA)
concentrations in plasma rapidly increased after oral BCAA supplementation both in groups 0 and 1. After discontinuing BCAA treatment,
a rapid reduction in these values was observed in group 1 patients. Closed circles, group 0; open circles, group 1. *P-0.05, **P-0.01
compared to the basal values; yP-0.05, yyP-0.01 compared to the values at 6 months.

improved between 3 and 6 months. After disconti-
nuing the BCAA supplementation, spontaneous oral
food intake as well as plasma albumin concentration
gradually decreased, but never to the baseline values.
However, anthropometric indices did not show an
apparent decrease. In group 0 patients, no improve-
ment in nutritional parameters was observed during
the placebo phase and serum albumin concentration
slightly decreased at 6 months. As in group 1, rapid
increases in appetite and oral protein and caloric
intakes, which were followed by increases in plasma
albumin concentration and anthropometric indices,
were observed after the BCAA therapy.
well by all patients, except one who had transient
diarrhoea for 2 days just after the administration of
BCAA granules. No other symptomatic complications
related to BCAA granule ingestion were observed in
any patients. Serum biochemical analysis revealed that
blood urea nitrogen level was insigni®cantly raised
during the amino acid therapy in groups 0 and 1.
Blood pH and bicarbonate concentrations were not
altered during amino acid therapy in either group (data
not shown).
Discussion

In this study we showed that anorectic, malnour-

Adverse effects
No patients underwent major surgery during the study
period or suffered from acute illness at the time of
the nutritional evaluation. At 9 months after the start
of this study, one patient in group 2 died suddenly
from pontine haemorrhage. At 10 months, one patient
in group 1 suffered from severe cerebral infarction
and was excluded from the rest of the study. During
the study period, two patients in group 0 and one
patient in group 1 were brie¯y (less than a week)
admitted to the hospital because of common cold and
acute bronchitis, and to undergo imaging studies such
as a barium enema. During the whole experimental
period, BCAA granule supplementation was tolerated
ished elderly patients had lower protein and caloric
intakes than did well-nourished patients or healthy
elderly subjects. It is vital to improve appetite and
increase oral food intake as a strategy for improving
malnutrition. However, elderly persons may suffer a
decline in the senses of smell and taste, dental problems
that decrease their ability to chew certain foods, and
loss of vision, all of which may make eating less
pleasant and lead to a decreasingly low appetite w3x.
Therefore, conventional therapies for poor appetite
such as dietary counselling and dietary supplementa-
tion are less likely to improve poor oral food intake in
the elderly. In fact, in this study frequent dietary
counselling during the baseline period were ineffective.
Branded-chain amino acids supply in elderly HD patients
In the general population receiving CHD, inad-
equate dialysis appears to result in impaired appetite
and decreased nutritional status w18x. However, a
weak positive correlation between dialysis ef®cacy
and spontaneous food intake in elderly CHD patients
has been reported in several studies w1,4x. We pre-
viously evaluated the effect of prospectively increasing
dialysis ef®cacy as a strategy for improving nutritional
status in elderly CHD patients, but could not show any
bene®t w2x. In fact, in this study dialysis ef®cacy
manifested by KtuV urea in malnourished patients
(groups 0 and 1) was adequate ()1.4) and was quite
similar to that in well-nourished patients (group 2).
Chronic in¯ammation is common especially in
elderly CHD patients and may cause atherosclerotic
cardiovascular disease such as chronic heart failure,
resulting in malnutrition w19x. In this study, patients
with vascular diseases such as myocardial infarction
and cerebral infarction were excluded. All patients
were outpatients and none had chronic heart fail-
ure. Also, there were no signi®cant differences in
serum C-reactive protein concentrations between the
well-nourished and malnourished groups.
Several factors such as leptin, insulin, nitric oxide
synthase inhibitors, proin¯ammatory cytokines, and
amino acid imbalances are possibly responsible for
appetite suppression in uraemia w20±22x. However, a
recent report showed a close relationship between
the augmentation of appetite and BCAA supplemen-
tation. Gill et al. w6x suggested that use of BCAA-
enriched parenteral nutrition might minimize the
reduction in food intake seen during intravenous
nutrition, possibly hastening the return to a normal
eating behaviour in healthy subjects. In this study,
lower BCAA levels in plasma were documented in
elderly anorectic patients compared to well-nourished
patients without anorexia; only BCAA was adminis-
tered in a relatively large dose to normalize the plasma
BCAA levels and to exclude the effects of other
nutrients such as glucose and lipid emulsion. As a
result, plasma BCAA levels increased rapidly in
patients receiving BCAA granules and soon became
higher than those in healthy subjects. Concomitantly,
all anorectic patients showed improved appetite, which
led to increases in oral protein and caloric intakes.
Good appetite persisted during the BCAA treatment
and the plasma BCAA levels were greater than those in
healthy subjects; however, after the therapy was
stopped, oral food intake decreased, followed by a
rapid decrease in plasma BCAA levels. This observa-
tion clearly demonstrates a tight correlation of plasma
BCAA level with appetite or voluntary food intake.
The mechanisms for the favourable effect of
increasing plasma BCAA levels on appetite may be
the following: administration of BCAA accentuates
the stimulation of respiration by amino acids, possibly
by competing with tryptophan for uptake across
the blood±brain barrier w23x. This competition may
decrease brain uptake of tryptophan, an amino acid
that serves as the precursor for serotonin, and thereby
decrease the synthesis of brain serotonin, a central
1861
respiratory depressant. It may be possible to modify
appetite by administering BCAA because serotonin
has been implicated as the neurotransmitter that
controls food intake w24x. Moreover, the BCAA
itself plays a central role in metabolism as a pre-
cursor for the synthesis of proteins, fatty acids,
metabolic fuel, regulations of protein turnover, and
insulin release w25x. Among BCAA, leucine stimu-
lates protein synthesis and its keto analogue inhibits
proteolysis due to inhibition of glucocorticoid syn-
thesis. In this regard, normalization of plasma
leucine concentration may also bene®t nutritional
status w26x.
Nutritional indices, especially anthropometric mea-
surements, began to improve 3 months after the start
of therapy, which is a shorter time span than those in
other reports w12±15x. Earlier reports showed that any
changes in nutritional parameters did not arise until
after 6±9 months of intradialysis parenteral nutrition
therapy. Rapid improvement of plasma BCAA levels
and oral food intake is of potential clinical signi®c-
ance due to the positive effect on protein synthesis,
which thereby shortens the required length of time
of nutritional treatment. After the cessation of the
therapy in group 1, nutritional indices began to
decrease, but never to the baseline values. Thus, oral
administration of BCAA granules gave rapid and
prolonged bene®ts for nutritional status. Our results
of anthropometric measurements using bioelectrical
impedance analysis should be interpreted with caution,
however, because Di Iorio et al. w27x reported that
a signi®cant error might occur in the measurement
of body composition from whole-body bioelectrical
impedance analysis when performed in certain situa-
tions in haemodialysed patients. However, in stable
CHD patients, except very obese subjects, Madore
et al. w28x reported that bioelectrical impedance ana-
lysis is accurate with high sensitivity and speci®city for
identifying malnourished patients.
Although our results are preliminary, they suggest
that there is a strong association between plasma
BCAA levels and appetite. Normalization of plasma
BCAA levels by oral supplementation was easily
and safely achieved and produced prompt and per-
sistent improvement of nutritional indices as well as
spontaneous oral food intake in elderly malnour-
ished patients. Modi®cations of this therapy, such
as increasing the length of treatment or providing
intermittent treatment on an as-needed basis, may be
considered. Certainly, it is too early to recommend
this therapy as a routine approach. Additional stud-
ies with larger numbers of patients and in conditions
of the general haemodialysis population will be
required.
References
1. Cianciaruso B, Brunori G, Traverso G et al. Nutritional status
in the elderly patients with uraemia. Nephrol Dial Transplant
1995; wSuppl 6x: 65±68
1862
2. Hiroshige K, Kabashima N, Kanegae K et al. Dialysis ef®cacy
and nutritional status in elderly hemodialyzed patients. Geriatr
Nephrol Urol 1997; 6: 149±158
3. Koehler KM, Garry PJ. Nutrition and aging. Clin Lab Med
1993; 13: 433±453
4. Movilli E, Filippini M, Brunori G et al. In¯uence of protein
catabolic rate on nutritional status, morbidity and mortality
in elderly uraemic patients on chronic haemodialysis. A pros-
pective 3-year follow-up study. Nephrol Dial Transplant 1995;
10: 514±518
5. Harper AE, Benevenga NJ, Wohlhueter RM. Effects of inges-
tion of disproportionate amounts of amino acids. Physiol Rev
1970; 50: 428±558
6. Gill KM, Skeie B, Kvetan V, Friedman M, Askanazi J.
Parenteral nutrition and oral intake. Effect of branched-chain
amino acids. Nutrition 1990; 6: 291±295
7. Kopple JD. Abnormal amino acid protein metabolism in uremia.
Kidney Int 1978; 14: 340±348
8. Young GA, Swanepoel CR, Croft MR, Hobson SM,
Parsons FM. Anthropometry and plasma valin, amino acids,
and proteins in the nutritional assessment of hemodialysis
patients. Kidney Int 1982; 21: 492±499
9. Carr SJ, Layward E, Bevington A, Hatterley J, Walls J. Plasma
amino acid pro®le in the elderly with increasing uraemia.
Nephron 1994; 66: 228±230
10. Phillips ME, Havard J, Howard JP. Oral essential amino
supplementation in patients on maintenance hemodialysis. Clin
Nephrol 1978; 9: 241±248
11. Hecking E, Kohler H, Zobel R et al. Treatment with essential
amino acids in patients on chronic hemodialysis. A double-blind
crossover study. Am J Clin Nutr 1978; 31: 1821±1826
12. Cano N, Labastie-Coeyrehourq J, Lacombe P et al. Peridia-
lytic nutrition with lipids and amino acids in malnourished
hemodialysis patients. Am J Clin Nutr 1990; 52: 726±730
13. Capelli JP, Kushner H, Camiscioli TC, Chen SM, Torres MA.
Effect of intradialytic parenteral nutrition on mortality rates
in end-stage renal disease care. Am J Kidney Dis 1994; 23: 808±816
14. Smolle K-H, Kaufmann P, Holzer H, Druml W. Intra-
dialytic parenteral nutrition in malnourished patients on chronic
haemodialysis therapy. Nephrol Dial Transplant 1995; 10:
1411±1416
K. Hiroshige et al.
15. Hiroshige K, Iwamoto M, Kabashima N, Mutoh Y, Yuu K,
Ohtani A. Prolonged use of intradialysis parenteral nutrition in
elderly malnourished chronic haemodialysis patients. Nephrol
Dial Transplant 1998; 13: 2081±2087
16. Morgan MY. Branched-chain amino acids in the management
of chronic liver disease. J Hepatol 1990; 11: 133±141
17. Daugirdas JT. The pos:pre plasma urea nitrogen ratio to
estimate KtV and NPCR validation. Int J Artif Organs 1989;
12: 420±427
18. Bergstrom J, Lindholm B. Nutrition and adequacy of dialysis.
How do hemodialysis and CAPD compare? Kidney Int Suppl
1993; 43: 39±50
19. Stenvinkel P, Heimburger O, Lindholm B, Kaysen GA,
Bergstrom J. Are there two types of malnutrition in chronic
renal failure? Evidence for relationships between malnutrition,
in¯ammation, and atherosclerosis (MIA syndrome). Nephrol
Dial Transplant 2000; 15: 953±960
20. Halaas JL, Gajiwala KS, Mafei M. Weight-reducing effects of
the plasma protein encoded by the obese gene. Science 1995;
269: 543±546
21. Plata-Salaman CR. Cytokines and anorexia. A brief overview.
Semin Oncol 1998; 25 wSuppl 1x: 64±72
22. Bergstrom J. Mechanisms of uremic suppression of appetite.
J Renal Nutr 1999; 9: 129±132
23. Takala J, Askanazi J, Weissman C et al. Changes in respiratory
control induced by amino acid infusions. Crit Care Med 1988;
16: 465±469
24. Blundell JE. Is there a role for serotonin (5-hydroxytryptamine)
in feeding? Int J Obes 1977; 1: 15±42
25. Adibi SA. Metabolism of branched-chain amino acids in altered
nutrition. Metabolism 1978; 25: 1287±1302
26. Riedel E, Hampl H, Nundel M, Farshidfar G.
Essential branched-chain amino acids and a-ketoanalogues
in haemodialysis patients. Nephrol Dial Transplant 1992;
4: 117±120
27. Di Iorio BR, Terracciano V, Bellizzi V. Bioelectrical
impedance measurement: errors and artifacts. J Renal Nutr
1999; 4: 192±197
28. Madore F, Wuest M, Ethier JH. Nutritional evaluation of
hemodialysis patients using an impedance index. Clin Nephrol
1994; 41: 377±382
Received for publication: 1.12.99
Accepted in revised form: 17.4.01