The Rationale of Intradialytic Amino Acid Supplementation

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Introduction

It has been long known that in general, patients with renal failure undergoing hemodialysis are almost  invariably  malnourished ^(1,2). It is estimated that approximately 40-50% of dialysis patients are malnourished and 10% of these patients experience severe malnutrition. Hypoalbuminemia is an independent risk factor for mortality in patients with maintenance hemodialysis.  Serum albumin  of <3.5 g / dl is followed by an increased risk of hospitalization and death than serum albumin 4 g / dl.

Patients without inflammation, malnutrition or CVD have  a mortality rate of 0% within 36 months, while the reverse has a mortality rate of 75% after 36 months ⁽¹⁾

The pathogenesis of malnutrition in patients with CKD

Various factors are involved in the occurrence of malnutrition. In addition to anorexia, HD led to an increase in the rate of whole body proteolysis (10%) and muscle protein (133%) ⁽³⁾.  Body protein synthesis   does not change, but the forearm protein synthesis increases (120%). The net result is a net loss of whole body protein increased (95%) and loss of forearm protein (164%).

Increased proteolysis is triggered by stress and inflammation. Proinflammatory cytokines such as interleukin-1, TNF and CRP have been shown elevated in HD patients ⁽³⁾ Other factors include acidosis and decreased albumin synthesis.  Ubiquitin-dependent and proteasome pathways during metabolic acidosis induce muscle proteolysis ⁽³⁾.

Obesity can aggravate the inflammatory process in patients with CKD. CRP levels> 3 mg / dl is observed 2.5 times higher in patients with HD who have a BMI> 30 kg / m² compared to a BMI <25 kg / m²

Hemodialysis procedure itself causes the loss of amino acids and proteins. The amount  of removed amino acids in hemodialysis process varies depending on the duration  of dialysis session, the membrane used and the presence or absence of amino acid supplementation. Navarro et al reported removed amino acids during a 4-hour HD session is 12 + 2 g (without  AA administration), followed by a decrease in plasma AA levels (386 + 298 mmol / L For EAA and 902 + 735 mmol / L for NEAA). After the supplementation of AA, the loss increased to 28 + 4 g. However, this procedure produced positive net AA balance (19.6 + 5.6 g AA in total), thereby preventing further decline of plasma concentrations. Moreover suiplementasi AA increased plasma levels of EAA by average of 14% and 27% BCAA ⁽⁴⁾.

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

High FLux vs Low Flux Membrane

The loss of Total AA , Essential AA and BCAA did not differ significantly on both types of membrane. The loss of alanine in the dialysate is greater at low flux membranes compared to high flux membranes ⁽²⁾.

IDPN versus Intradialytic  Amino Acid Supplementation

IDPN has been widely used in the past but limited by the need to meet the entire nutrient infusion during HD, and the potential adverse effects due to fast administration of glucose and lipid. Therefore, this modality often fails to meet the nutritional needs of patients with intestinal failure and limited oral intake and also has the risk of refeeding syndrome.Although IDPN has been associated with weight gain and increased levels of albumin, studies have not shown the benefit of IDPN in reducing mortality. IDPN with moderate amount of calories may still have a place. Hanafusa et al using 200 ml of 7.2% solution of amino acids (KidminTM), 200ml of 50% glucose and 20% lipid emulsion as a liquid IDPN. Loss of AA on the HD session was calculated 9.171.4g, ie less than the infused as IDPN. ⁽⁵⁾

The latest recommendation is Intradialytic parenteral nutrition should not be used as a regular supplement on-stage V CKD patients undergoing hemodialysis. ⁽⁶⁾

On the other hand, amino acid supplementation during dialysis is intended to replace the loss of amino acids by hemodialysis process and prevent a further decrease in plasma AA levels.

Which Amino Acids?

EAA at doses above 0.5 g / kg / day was reprted to have  a higher risk for the occurrence of metabolic hyperammonemia and hepatic encephalopathy, because arginine, ornithine, and citrulline were not supplied. These three  non-essential amino acids are needed for the detoxification of ammonia in the Krebs Urea cycle. As a result, a solution containing a mixture of essential amino acids and non-essential amino acids  is recommended ⁽⁷⁾

In renal failure, BCAA status is characterized by low levels of valine in plasma and cells, as well as low plasma levels of leucine and isoleucine. The Abnormality of BCAA plasma and intracellular levels occur secondary to abnormal muscle and hepatosplanschnic amino acid metabolism. In muscle, metabolic acidosis results in proteolysis via activation of  1) cytosolic ATP-ubiquitin–dependent pro-teolytic pathway and 2) BCKA dehydrogenase, responsible for irreversible BCAA breakdown ⁽⁸⁾. Therefore, in addition to containing a mixture of EAA and NEAA , amino acid solutions for intradialytic supplementation should contain high  BCAA.

References:

1. Fuhrman MP .Intradialytic Parenteral Nutrition and Intraperitoneal Nutrition. Nutrition in Clinical Practice / Vol. 24, No. 4, August/September 2009
2. Gil HW, et al. The Effect of Dialysis Membrane Flux on Amino Acid Loss in Hemodialysis Patients. J Korean Med Sci 2007; 22: 598-603
3. Ikizler TA, et al. Hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation. Am J Physiol Endocrinol Metab 282:E107–E116,2002
4. Navarro JF ,et al. Amino acid losses during hemodialysis with polyacrylonitrile membranes: effect of intradialytic amino acid supplementation on plasma amino acid concentrations and nutritional variables innondiabetic patients. Am J Clin Nutr2000;71:765–73
5. Hanafusa N, et al. AMINO ACID REMOVAL DURING HEMODIALYSIS OF PATIENTS WHO HAD UNDERGONE INTRADIALYTIC PARENTERAL NUTRITION. Kidney Res Clin Pract 31(2012)A16–A96
6. Brown RO , Compher C. A.S.P.E.N. Clinical Guidelines: Nutrition Support in Adult Acute and Chronic Renal Failure. Journal of Parenteral and Enteral NutritionVolume 34 Number 4July 2010 366-377© 2010 American Society for Parenteral and Enteral Nutrition
7. Kalista-Richards M.The Kidney: Medical Nutrition Therapy—Yesterday and Today Nutrition in Clinical Practice Volume 26 Number 2April 2011 143-150
8. Cano NJM, Fouque D, Leverve XM. Application of Branched-Chain Amino Acids in Human Pathological States: The Journal of Nutrition; Jan 2006; 136, 1SRenal Failure.