NDT Advance Access originally published online on March 5, 2004
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Nephrol Dial Transplant (2004) 19: 1520-1527
Nephrol Dial Transplant Vol. 19 No. 6 © ERA-EDTA 2004; all rights reserved
Original Article
Abnormal mitochondrial function and muscle wasting, but normal contractile efficiency, in haemodialysed patients studied non-invasively in vivo
1Department of Musculoskeletal Science, 2Magnetic Resonance and Image Analysis Research Centre and 3Department of Medical Imaging, University of Liverpool, Liverpool, 4Renal Unit, Royal Liverpool University Hospital, Liverpool and 5Countess of Chester Hospital NHS Trust, Chester, UK
Correspondence and offprint requests to: G. J. Kemp, Department of Musculoskeletal Science, University of Liverpool, Liverpool L69 3GA, UK. Email: gkemp{at}liv.ac.uk.
Background. Muscle dysfunction, which contributes to morbidity in patients on haemodialysis, has several manifestations and a number of possible causes. We applied the non-invasive techniques of 31P-magnetic resonance spectroscopy (31P-MRS), magnetic resonance imaging (MRI) and near-infrared spectroscopy (NIRS) to calf muscle of dialysed patients to define the abnormalities in muscle cross-sectional area (CSA), contractile efficiency, mitochondrial function and vascular O2 supply.
Methods. We performed 31P-MRS/NIRS/MRI studies on the lateral gastrocnemius during isometric plantarflexion and recovery in 23 male patients on haemodialysis (age 24–71 years; haemoglobin 9.9–14.2 g/dl; bicarbonate 17–30 mmol/l; urea reduction ratio 53–77%; parathyroid hormone 1–95 U/l) and 15 male controls (age 29–71 years). To understand the relationships between calf CSA and body mass we also performed MRI only in a further six male patients and 18 male controls.
Results. In patients, exercise duration was 30±11% lower than in controls. Muscle CSA was lower by 26±5%, but contractile efficiency (force/CSA/ATP turnover) was normal. Slowing of post-exercise phosphocreatine (PCr) recovery implied a 22±5% defect in effective ‘mitochondrial capacity’. That PCr recovery was slow relative to NIRS recovery suggests that this is largely an intrinsic mitochondrial problem (not the result of impaired O2 supply), one which, furthermore, correlated with CSA. Urea reduction ratio showed a negative correlation with body mass and CSA, but none with PCr rate constant.
Conclusions. The relationships to urea reduction ratio reflect the effect of muscle mass on dialysis efficiency, rather than direct effects on muscle CSA or metabolism. The relationship between PCr recovery and calf CSA suggests a role for the mitochondrial defect, whatever its cause, in the development of muscle wasting, although a common cause (e.g. physical inactivity) for both abnormalities cannot be ruled out.
Keywords: haemodialysis; magnetic resonance spectroscopy; mitochondria; near-infrared spectroscopy
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