Nutrition in CAPD: serum bicarbonate and the ubiquitin-proteasome system in muscle.
BACKGROUND
Metabolic acidosis in chronic renal failure (CRF) induces loss of lean body mass while elimination of acidosis during a one year trial improved anthropometric indices in continuous ambulatory peritoneal dialysis (CAPD) patients. In rats with CRF, the mechanisms causing loss of lean body mass have been linked to acidosis-induced destruction of the essential, branched-chain amino acids (BCAA) and activation of the ubiquitin-proteasome system that degrades muscle protein; the latter response includes increased transcription of the ubiquitin gene.


METHODS
Our aim was to determine if increasing the serum bicarbonate (HCO3) concentration of CAPD patients would improve their nutritional status, increase plasma BCAA levels, and reduce ubiquitin mRNA in their muscle as an index of suppressed activity of the ubiquitin-proteasome system. Eight, stable, long-term CAPD patients underwent vastus lateralis muscle biopsy before being randomized to continue 35 mmol/L lactate dialysate or convert to a 40 mmol/L lactate dialysate. After four weeks, measurements were repeated.


RESULTS
Serum HCO3 increased in all patients and final values did not differ statistically between the two groups so results for all patients were combined. Weight and body mass index increased significantly as did plasma BCAA. Muscle levels of ubiquitin mRNA decreased significantly; serum tumor necrosis factor-alpha (TNF-alpha) also decreased.


CONCLUSIONS
Our results indicate that even a small correction of serum HCO3 improves nutritional status, and provide evidence for down-regulation of BCAA degradation and muscle proteolysis via the ubiquitin-proteasome system. Whether acidosis and inflammatory cytokines (such as, TNF-alpha) interact to impair nutrition is unknown.
Pickering
Warren P
WP
Department of Nephrology, Leicester General Hospital, Leicester, England, United Kingdom.
Price
S Russ
SR
Bircher
Gemma
G
Marinovic
Anne C
AC
Mitch
William E
WE
Walls
John
J
D000136:Acid-Base Equilibrium; D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000097:blood; D001639:Bicarbonates / Q000097:blood*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009747:Nutritional Physiological Phenomena; D009752:Nutritional Status; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011446:Prospective Studies; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
D000597:Amino Acids, Branched-Chain; D001639:Bicarbonates; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex