Effect of bicarbonate on muscle protein in patients receiving hemodialysis

Am J Kidney Dis. 2006 Sep;48(3):419-29. doi: 10.1053/j.ajkd.2006.05.029.


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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis
  • Aged
  • Amino Acids / blood
  • Female
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Phenylalanine / metabolism
  • Renal Dialysis*


  • Amino Acids
  • Muscle Proteins
  • Phenylalanine