An increase in circulating levels of branched-chain amino acids during hemodialysis with regard to protein breakdown: three case reports

Abstract

Background Hemodialysis (HD) is a protein catabolic event. However, the amino acid (AA) kinetics during HD sessions involved in protein breakdown have not been well investigated in patients with and without diabetes mellitus (DM). Case presentation Three patients (two patients with DM and one patient without DM) underwent fasting HD. Plasma levels of branched-chain AAs (BCAA; leucine, isoleucine, and valine), major non-essential AAs (alanine and glutamine, including glutamate), insulin, and ketone bodies were measured every hour during each HD session. After the start of the HD session, the plasma levels of insulin and all BCAAs dropped simultaneously. There was a significant subsequent increase in the plasma level of leucine and isoleucine levels, while valine levels remained constant. However, the recovery in levels of BCAAs during HD indicated a profound amount of BCAAs entering the blood from body tissues such as muscles. BCAAs may have surpassed their removal by HD. Ketone body levels increased continuously from the start of the sessions and reached high values in patients with DM. Synchronous changes in insulin depletion and an increase in the levels of ketone bodies may indicate disruption of energy metabolism. Conclusions This is the first report to demonstrate the time course of the changes in circulating levels of BCAAs and related metabolites in energy homeostasis during HD. An increase in BCAA levels during HD was found to be due to their transfer from the body tissue which suggested protein breakdown.

Amino acid availability enhanced through glucose coadministration of amino acid supplementation during hemodiafiltration: two case reports

“…This significantly high level of KB might correspond to pathophysiological starvation [22,23]. As mentioned in introduction, the increase of plasma levels of KB during treatments in patients with diabetes mellitus have been reported [14,15], and underlined mechanism of them were suggested to be cell starvation. Circulating KB appears during starvation when the depletion of insulin induces free fatty acid release from adipose tissue, and β-oxidation is accelerated in the liver.…”

“…The plasma levels of the following molecules were quantified in these samples: major components of NEAAs (alanine [Ala], glutamine, and glutamate), three BCAAs (Ile, Leu, Val), glucose, and immunoreactive insulin (IRI). As glutamine is easily converted to glutamate in normal laboratory settings [13,15], the sum of the glutamine and glutamate levels was evaluated as glutamine-glutamate (Glx) levels. In the dialysate samples, three BCAAs, Ala, and Glx were measured using the same method as for blood, and ketone bodies (KB; including 3-hydroxy butyrate and acetoacetate) were measured using quantitative 1 HNMR spectroscopy of dialysate and converted to plasma levels [14][15][16].…”

“…In a previous study, we found that HD or HDF induced disruption of energy homeostasis through rapid depletion of insulin and elevation of ketone bodies in plasma, which often invoked cell starvation [14,15]. In addition, plasma levels of branched-chain AAs (BCAA) were found to increase after the first hour of the fasting HD session [15].…”

“…In a previous study, we found that HD or HDF induced disruption of energy homeostasis through rapid depletion of insulin and elevation of ketone bodies in plasma, which often invoked cell starvation [14,15]. In addition, plasma levels of branched-chain AAs (BCAA) were found to increase after the first hour of the fasting HD session [15]. BCAAs belong to the essential AA (EAA) group, and EAAs have no in vivo biosynthesis; therefore, the increase in plasma BCAA levels during dialysate was suggested to originate from the free AA pool along with body protein breakdown.…”