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The Rationale of Intradialytic Amino Acid
Supplementation
dr Iyan Darmawan
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 differenceFAO: Food and Agricultural Organization
Roles of amino acidsmgN/kg/day Total
Urine 37 54 mg/kg/day
Stool 12Skin 3Other 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
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):558-5622) 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:p1233)幕内晴朗:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):442-4454)福井康三,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):438-4415)池田弘人,小林国男:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):706-7096)貞広智仁,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):693-6967)本渡幾久子,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):663-6668)大貫 隆子,他:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):659-6629)標葉隆三郎:日本臨牀 静脈・経腸栄養 2001;59(Suppl.5):136-140
Appropriate nitrogen source
Adequate calorie
Glucose, lipid
Prevention of body protein destruction due to hypercatabolismPrevention 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
Essential and Non-essential Amino Acids
EssentialAmino acids
Non-essentialAmino acids
+ Energy
Expired Air
BreakBody proteins Energy + Urea + H2O + CO2
Down
15 – 20 g protein/day in diet
Nitrogen equilibrium or positivenitrogen balance is achieved andUrea levels are allowed
Urine
Synthesis
Synthesis
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
Naw/v%
g/dL
mEq/L+
Composition EAA SOl
1125720820820
11251125515255
---------13
7.060.911.637.7
560
w/w%
Am
ino
acid
s
L-LeucineL-IsoleucineL-ValineL-LysineL-MethionineL-PhenylalanineL-ThreonineL-Tryptophan L-HistidineL-ArginineL-Asparaginic acidL-Glutamic acidL-AlanineL-CysteineAmino acetateL-ProlineL-SerineL-Tyrosine
Concentration of total free amino acids N level E/N ratio BCAA content
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
AmmoniumATP
Bicarbonate
ADP
Ornithine carbamyl transferase
Urea Arginase
Argininosuccinase
Carbamyl phosphate
Carbamyl phosphate synthetase
CitrullineOrnithine
Ornithine Citrulline
Arginine Argininosuccinic acidOrotic acid
Carbamyl phosphate
Carbamyl Asparaginic acid
Fatty liver
Dysfunction of urea circuit
Accumulation of carbamyl
phosphate
Accumulation of ammonium
Neutral fat, VLDLDisturbance of transportation
Increase of orotic acid
Consciousness disorder
Coma
Mitochondria
Cytoplasma
Argininosuccinic acidSynthetic 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
Benefits
Removal of uremic toxinβ2-microglobulin, intermediate-molecular substances, etc.
Removal of nitrogenous metabolites Urea, uric acid, creatinine, etc.Increase of protein intake
Demerits o HDLoss of amino acidsLoss of water-soluble vitamins and substances necessary for protein/amino acid metabolismSecretion of invasive hormones under stress Cortisol, catecholamine, glucagon, etc.Decrease in blood circulation in tissues Extracorporeal circulation, blood pressure decreaseDisturbance of cellular metabolism Rapid change of intracellular water content and osmotic pressureHypercatabolism 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
◎
◎
◎
◎
◎
◎
◎
◎
◎
0.3
0.2
0.1
0
EAA/TAA0.15
0.10
0.05
0
BCAA/TAA1.5
1.0
0.5
0
Val/Gly1.0
0.5
0
Ser/Gly1.5
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
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
AA Loss during Dialysis
Membrane AA Loss
Low-flux cuprophane 7,2 + 2,6 g(Terumo T150)Low-flux polymethyl- 6,1 + 1,5 gmethacrylate (Toray B2)High-flux polysulfone 8,0 + 2,8 g(Fresenius F80)
Rully Rusli. 2nd xpert Meeting on Clinical Nutrition
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
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
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
Malnourished
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
BCAA in CRF
• s
Cano et al. J. Nutr.136:299S-307S.2006
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
Thanks
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