Effect of bicarbonate on muscle protein in patients receiving hemodialysis.
BACKGROUND
Metabolic acidosis stimulates whole-body net protein breakdown in healthy adults and patients with kidney failure, but few studies investigated how acidosis affects protein metabolism in individual tissues, such as skeletal muscle.


METHODS
We evaluated the effect of metabolic acidosis on protein turnover in skeletal muscle, assessed by means of phenylalanine kinetics and free amino acid concentrations in plasma and muscle. Long-term hemodialysis patients (n = 16) were divided into 2 groups in an open crossover study design. In group A, we administered bicarbonate supplements and increased blood standard bicarbonate levels from 17.8 +/- 0.03 to 27.1 +/- 1.2 mEq/L (17.8 +/- 0.03 to 27.1 +/- 1.2 mmol/L). In group B, we decreased bicarbonate supplements, which caused a decrease in standard bicarbonate levels from 26.6 +/- 0.7 to 18.6 +/- 0.3 mEq/L (26.6 +/- 0.7 to 18.6 +/- 0.3 mmol/L).


RESULTS
Net phenylalanine efflux from leg tissues (muscle) was significantly less when acid-base balance was corrected compared with acidosis (10.8 +/- 1.5 versus 18.6 +/- 3.8 nmol/min/100 g tissue; P = 0.014), as was the rate of phenylalanine appearance (28.3 +/- 3.0 versus 38.4 +/- 5.9 nmol/min/100 g tissue; P = 0.016); the rate of phenylalanine disposal was unchanged. Cortisol and C-reactive protein levels in blood were unchanged after correction of acidosis, as were levels of messenger RNAs encoding components of the ubiquitin-proteasome pathway in muscle biopsy specimens.


CONCLUSIONS
Our findings indicate that acidosis increases protein breakdown in skeletal muscle, but additional studies are needed to identify the pathways stimulated to degrade muscle protein in response to acidosis.
Löfberg
Erland
E
Department of Clinical Science, Intervention, and Technology, Division of Renal Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Gutierrez
Alberto
A
Anderstam
Björn
B
Wernerman
Jan
J
Bergström
Jonas
J
Price
S Russ
SR
Mitch
William E
WE
Alvestrand
Anders
A
D000138:Acidosis; D000368:Aged; D000596:Amino Acids / Q000097:blood; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D006435:Renal Dialysis
D000596:Amino Acids; D009124:Muscle Proteins; D010649:Phenylalanine