1. Nutrition in CAPD: Serum bicarbonate and the ubiquitin-proteasome system in muscle
- Author
-
Warren Pickering, William E. Mitch, S. Russ Price, Gemma Bircher, Anne C. Marinovic, and John Walls
- Subjects
Male ,Proteasome Endopeptidase Complex ,medicine.medical_specialty ,Vastus lateralis muscle ,medicine.medical_treatment ,030232 urology & nephrology ,Down-Regulation ,Nutritional Status ,Protein degradation ,Peritoneal dialysis ,03 medical and health sciences ,0302 clinical medicine ,Peritoneal Dialysis, Continuous Ambulatory ,chronic renal failure ,Multienzyme Complexes ,Internal medicine ,diet and dialysis ,medicine ,Humans ,Nutritional Physiological Phenomena ,Prospective Studies ,RNA, Messenger ,branched-chain amino acids ,Muscle, Skeletal ,Aged ,030304 developmental biology ,Acidosis ,Acid-Base Equilibrium ,2. Zero hunger ,0303 health sciences ,Ubiquitin ,business.industry ,Continuous ambulatory peritoneal dialysis ,Metabolic acidosis ,Middle Aged ,medicine.disease ,3. Good health ,Bicarbonates ,Cysteine Endopeptidases ,Endocrinology ,Nephrology ,protein degradation ,Lean body mass ,Female ,acidosis ,medicine.symptom ,business ,Body mass index ,Amino Acids, Branched-Chain - Abstract
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. Method Our aim was to determine if increasing the serum bicarbonate (HCO 3 ) 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 HCO 3 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-α (TNF-α) also decreased. Conclusion Our results indicate that even a small correction of serum HCO 3 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-α) interact to impair nutrition is unknown.
- Published
- 2002