Balanced Amino Acids. EAA/NEAA ratio 2.6 is required to prevent hyperammonemia Replaces amino acid loss during dialysis High BCAA to improve the amino acid profile IDPN containing protein,CHO dan Lipid should not routinely used...but the administration of Balanced AA alone is justified

1. The Rationale of
Intradialytic Amino Acid
Supplementation
dr Iyan Darmawan

2. Unavoidable nitrogen loss (FAO/WHO)
*:0.054(g) ×7.5* × 60(kg) × 1.3**=31.6(g)
*: When nitrogen is converted to the amino acid volume
(6.25 × 1.2)
**: Usually 30% increase in consideration of individual
difference
FAO: Food and Agricultural Organization
Roles of amino acids
mgN/kg/day Total
Urine 37 54 mg/kg/day
Stool 12
Skin 3
Other 2
When converted amino
acids
(Human weighing 60 kg)
31.6 g/day*
Materials for protein
synthesis
Improvement of nitrogen
accountability
Improvement of protein
metabolism
Prevention of postoperative
complications
 Improvement of treatment
performance
Significance of administering amino acids
編集／必須アミノ酸研究委員会：エネルギー・蛋白質の必要性，医歯薬出版 1989：p46‐48

3. Ruptured suture/gastrointestinal fistula
170 to 2301)
Neonate/babies 230 to 2502)
After thoracic surgery 150 to 2003)
Cardiac cachexia 120 to 1904)
Heat burn 100 to 1205)
Multiple organ failure 150 to 2006)
Concomitant renal failure 200 to 3006)
Renal failure CRF Around 3007)
ARF 500 or over8)
General non-invasive disease
150 to2009)
Mildly invasive disease
150 to 2009)
Moderately invasive disease
100 to 1509)
Mildly invasive disease
80 to 1009)
Disease-specific NPC/N ratio
1）加固紀夫,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):558-562
2) 山内 健,矢加部 茂:実践静脈栄養と経腸栄養,エルゼビア・ジャパン;2005:p123
3）幕内晴朗:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):442-445
4）福井康三,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):438-441
5）池田弘人,小林国男:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):706-709
6）貞広智仁,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):693-696
7）本渡幾久子,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):663-666
8）大貫 隆子,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):659-662
9）標葉隆三郎:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):136-140

4. Appropriate
nitrogen source
Adequate calorie
Glucose, lipid
Prevention of body protein
destruction due to
hypercatabolism
Prevention the accumulation of
nitrogenous metabolites
Prevent the accumulation of
nitrogenous metabolites and
maintain nitrogen balance!
Problems in the administration of amino acids in the patients
with renal failure
寺岡 慧,太田和夫：救急医学 1993；17：1557-1562

5. Essential and Non-essential Amino Acids
Essential
Amino acids
Non-essential
Amino acids
+ Energy
Expired Air
Break
Body proteins Energy + Urea + H2O + CO2
Down
15 – 20 g protein/day in diet
Nitrogen equilibrium or positive
nitrogen balance is achieved and
Urea levels are allowed
Urine
Synthesis
Synthesis

6. Composition of EAA sol
 Administration of a small amount of
essential amino acids in high-calorie low-
protein diet prevents catabolism and the
amino acids as well as produced non-
essential amino acids are used for
protein synthesis.
 Azotemia and uremic symptoms are
alleviated by the reuse of endogenous
urea.
 Ammonium produced from the urea in
the intestinal tract is reabsorbed and
used for the synthesis of non-essential
amino acids in the liver.
 At present, urea is reused by not more
than a few percent and it is considered
impossible to maintain the nitrogen
balance at this dose.
Essential amino acid therapy (Endogenous urea reuse hypothesis)
菅 英育,他：消化器外科 1992；15：637‐645
Na
w/v%
g/dL
mEq/L+
Composition EAA SOl
1125
720
820
820
1125
1125
515
255
-
-
-
-
-
-
-
-
-
13
7.06
0.9
11.6
37.7
560
w/w%
Aminoacids
L-Leucine
L-Isoleucine
L-Valine
L-Lysine
L-Methionine
L-Phenylalanine
L-Threonine
L-Tryptophan
L-Histidine
L-Arginine
L-Asparaginic acid
L-Glutamic acid
L-Alanine
L-Cysteine
Amino acetate
L-Proline
L-Serine
L-Tyrosine
Concentration of total free
amino acids
N level
E/N ratio
BCAA content

7. Reason to add NEAA to EAA
EAA pada dosis diatas 0.5 g/kg/hari memiliki risiko lebih tinggi untuk terjadinya
hiperamonemia dan ensefalopati metabolik, karena arginin, ornitin, dan sitrulin
tidak dipasok. Ketiga asam amino non-esensial ini dibutuhkan untuk
detoksifikasi amonia dalam sikuls Urea . Akibatnya larutan yang mengandung
campuran asam amino esensial dan non-esensial dianjurkan
Kalista-Richards Nutrition in Clinical Practice Volume 26 Number 2April 2011 143-150

8. Ammonium
ATP
Bicarbonate
ADP
Ornithine carbamyl
transferase
Urea
Arginase
Argininosuccinase
Carbamyl phosphate
Carbamyl phosphate synthetase
CitrullineOrnithine
Ornithine Citrulline
Arginine Argininosuccinic acid
Orotic acid
Carbamyl
phosphate
Carbamyl
Asparaginic acid
Fatty liver
Dysfunction of urea circuit
Accumulation of
carbamyl
phosphate
Accumulation
of ammonium
Neutral fat, VLDL
Disturbance of
transportation
Increase of
orotic acid
Consciousness
disorder
Coma
Mitochondria
Cytoplasma
Argininosuccinic acid
Synthetic enzyme
Decrease in arginine
concentration
Mechanism of action of hyperammonemia and fatty liver
菅 英育,他：消化器外科 1992；15：637‐645

9. Benefits
Removal of uremic toxin
β2-microglobulin, intermediate-molecular substances, etc.
Removal of nitrogenous metabolites
Urea, uric acid, creatinine, etc.
Increase of protein intake
Demerits o HD
Loss of amino acids
Loss of water-soluble vitamins and substances necessary for
protein/amino acid metabolism
Secretion of invasive hormones under stress
Cortisol, catecholamine, glucagon, etc.
Decrease in blood circulation in tissues
Extracorporeal circulation, blood pressure decrease
Disturbance of cellular metabolism
Rapid change of intracellular water content and osmotic pressure
Hypercatabolism caused by hemodialysis itself
Effects on protein/amino acid metabolism during
hemodialysis
申 性孝ほか：日本臨牀,50（増刊号）,536,1992
◎
◎
◎
◎
◎
◎
◎
◎
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10. 0.3
0.2
0.1
0
EAA/TAA
0.15
0.10
0.05
0
BCAA/TAA
1.5
1.0
0.5
0
Val/Gly
1.0
0.5
0
Ser/Gly
1.5
1.0
0.5
0
Tyr/Phe
*
*
*
*
*
*:p<0.05(Mean±S.D.)Healthy
people (n=20)
Patients under dialysis
(n=15)
Abnormality of plasma amino acid metabolism
in the patients under long dialysis
鈴木 正司：胃と透析，33（臨時増刊号），566，1992

11. A.S.P.E.N. Clinical Guidelines: Nutrition Support in
Adult Acute and Chronic Renal Failure
• Intradialytic parenteral nutrition should not be used as a nutritional
supplement in malnourished chronic kidney disease-V hemodialysis
patients.(Grade: C)
• The recommended protein intake for patients who receive
maintenance HD is 1.2 g/kg/d and for those who receive CAPD...
1.3 g/kg/d
• Stage III or IV CKD have partial renal function and may require
restrictions in protein intake to as low as 0.3–0.6 g/kg/d to delay the
progression of renal disease
Brown RO, Compher C. JPEN Vol 34,No.4, July 2010

12. AA Loss during Dialysis
Membrane AA Loss
Low-flux cuprophane 7,2 + 2,6 g
(Terumo T150)
Low-flux polymethyl- 6,1 + 1,5 g
methacrylate (Toray B2)
High-flux polysulfone 8,0 + 2,8 g
(Fresenius F80)
Rully Rusli. 2nd xpert Meeting on Clinical Nutrition

13. Author Membrane Length of HD
session(hr)
Amino acid loss
Navarro polyacrylonitrile 3 6 g (membrane
0.9 m2)
Tepper T, Ikizler,
GomeZ P
Cellulose 4 4 -13 g
Izikler polyacrylonitrile 4 12 g
(membrane 1.7
m2)
Ikizler polysulfone 4 8 + 2.8 g
Ikizler polymethylmethacrylate 4 6.1 + 1.5 g
AA Loss during Dialysis
Navarro ,et al. Am J Clin Nutr2000;71:765–73

14. AMINO ACID REMOVAL DURING HEMODIALYSIS OF
PATI-ENTS WHO HAD UNDERGONE INTRADIALYTIC
PARENTERAL NUTRITION
• 200 ml of 7.2% amino acid solution(KidminTM),
• 200 ml of 50 % glucose, and 20% of lipid
emulsion as IDPN fluid
Norio Hanafusa, et al. Kidney Res Clin Pract 31(2012)A16–A96
Amino acid removal 9.1 + 1.4 g

15. Decreased BCAA in patients
undergoing HD > 2 years
Fisher ratio in HD Patients in relation to duration of HD
treatment and Nutritional Status
HD
Patients
< 2
years
>2
years
Well-
nourished
Malnou
rished
Control
Subjects
BCAA 258.7 296.8 237.2 268.3 242.3 323
AAA 95.6 101.4 92.2 94.9 96.7 105.4
Fisher
ratio
2.7 2.9 2.5 2.8 2.5 3.0
Margozewicz S. Journal of Renal Nutrition,Vol 18 No.2 (March) 2008 : pp239-247

16. BCAA in CRF
• s
Cano et al. J. Nutr.136:299S-307S.2006

17. Take Home Message
• Balanced Amino Acids. EAA/NEAA ratio 2.6 is
required to prevent hyperammonemia
• Replaces amino acid loss during dialysis
• High BCAA to improve the amino acid profile
• IDPN containing protein,CHO dan Lipid should not
routinely used...but the administration of Balanced
AA alone is justified

18. Thanks