Muscle insulin-like growth factor status, body composition, and functional capacity in hemodialysis patients.
BACKGROUND
Hemodialysis (HD) patients typically have reduced muscle mass and diminished functional capacity. The role of the muscle insulin-like growth factors (IGFs), a principal anabolic system that is involved in protein synthesis and that has downregulation that is implicated in muscle loss in animal models of uremia, has previously not been assessed in vivo in HD patients.


METHODS
Seventeen HD patients were compared cross-sectionally with 17 age-, sex-, and body mass index-matched healthy controls. Body composition was assessed by dual energy x-ray absorptiometry and bioelectrical impedance spectrometry; functional capacity by hand grip strength, quadriceps strength, and 30-second sit-to-stand test; systemic inflammation by tumor necrosis factor-alpha (TNF-alpha) and TNF receptor 1 (TNFR1); serum and muscle IGF-I and IGFBP-3 by radioimmunoassay; and fragmentation of serum IGFBP-3 by Western immunoblotting.


RESULTS
Appendicular lean mass was significantly decreased in HD patients compared with controls (17.6 +/- 0.9 versus 21.5 +/- 1.5 kg, P < .05), as were all measures of functional capacity (P < .01 to .001), and highly significant positive correlations between appendicular lean mass and functional capacity were evident (appendicular lean mass and hand-grip strength, quadriceps strength, 30-second sit-to-stand test, all P < .001). TNF-alpha and TNFR1 were elevated in patients (P < .001). Although serum IGF-I and IGFBP-3 levels did not differ between the groups (P = .295 and .379 respectively), fragmented IGFBP-3 levels were increased (53.1 +/- 16.0 versus 29.81 +/- 15.3%, P < .005). In contrast, muscle IGF-I was substantially diminished in the patient group (n = 7) relative to control (n = 5) levels (0.84 +/- 0.06 versus 2.78 +/- 1.80 pg/microg, P < .05).


CONCLUSIONS
We provide evidence of reduced IGF-I in HD patients' skeletal muscle that may be a causal factor in the muscle wasting characteristic of this population. Future research should determine the exact consequences and causes of alterations to the muscle IGF system in HD patients.
Macdonald
Jamie H
JH
School of Sport, Health, and Exercise Sciences, University of Wales-Bangor, Bangor, Gwynedd, Wales. pepc0a@bangor.ac.uk
Phanish
Mysore K
MK
Marcora
Samuele M
SM
Jibani
Mahdi
M
Bloodworth
Lionel L O
LL
Holly
Jeffrey M P
JM
Lemmey
Andrew B
AB
D001706:Biopsy; D001823:Body Composition; D015992:Body Mass Index; D002149:Energy Intake; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I