Effect of chronic uraemia on skeletal muscle metabolism in man

Nephrol Dial Transplant. 1993;8(3):218-22.


Fatigue and lethargy, common symptoms in uraemia, have been attributed to many factors. To assess possible bioenergetic contributions to this, we examined the forearm muscle of five patients in end-stage renal failure using 31P-magnetic resonance spectroscopy. There was a small increase in the ratio of intracellular inorganic phosphate to ATP in resting muscle, suggesting an increased cytosolic phosphate concentration. During exercise, increased phosphocreatine breakdown was accompanied by rapid intracellular acidification and an increase in calculated lactic acid accumulation in the muscle of the uraemic subjects, suggesting glycolysis dominating over oxidative phosphorylation as a source of ATP. After exercise, the half-time of phosphocreatine (PCr) recovery was longer in the uraemic subjects, suggesting diminished mitochondrial function. The initial rate of PCr resynthesis was not significantly decreased, but when account was taken of the high cytosolic ADP concentration (which drives mitochondrial oxidative ATP synthesis) the calculated maximum oxidative capacity was significantly reduced in the uraemic subjects. Thus there was evidence of mitochondrial dysfunction in uraemia due either to limitation of oxygen supply, reduced mitochondrial content, or an intrinsic mitochondrial defect. This resulted in increased phosphocreatine depletion and increased glycolytic ATP production during exercise and there was partial compensation of the mitochondrial abnormality by increased ADP concentration. In three of these patients studied after elevation of haemoglobin with erythropoeitin (from 8 to 12 g/dl), initial phosphocreatine breakdown and lactic acid accumulation during exercise were normalized, while exercise duration and calculated maximum oxidative capacity remained significantly abnormal. This suggests that anaemia contributes to these metabolic abnormalities but does not fully explain them.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analysis
  • Adenosine Triphosphate / biosynthesis
  • Aged
  • Anemia / metabolism
  • Chronic Disease
  • Energy Metabolism*
  • Exercise
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney Failure, Chronic / metabolism*
  • Lactates / metabolism
  • Lactic Acid
  • Male
  • Middle Aged
  • Muscles / blood supply
  • Muscles / metabolism*
  • Phosphocreatine / analysis
  • Uremia / metabolism*


  • Lactates
  • Phosphocreatine
  • Lactic Acid
  • Adenosine Triphosphate