Skeletal muscle mRNA for IGF-IEa, IGF-II, and IGF-I receptor is decreased in sedentary chronic hemodialysis patients.

Maintenance hemodialysis patients often display evidence for protein-energy malnutrition, inflammation, and sarcopenia. We therefore investigated whether sedentary maintenance hemodialysis patients have decreased skeletal muscle mRNA levels and muscle and serum protein concentrations of certain growth factors. Fifty-one clinically stable maintenance hemodialysis patients (32 men and 19 women), and 21 normal adults (16 men and five women) of similar age, gender mix, racial/ethnic backgrounds, serum albumin, body composition, and level of sedentary activity were studied. Individuals underwent biopsy of the right vastus lateralis muscle, and real-time polymerase chain reaction (PCR) amplification of mRNAs for insulin-like growth factor-I (IGF-I), IGF-II, IGF-I receptor (IGF-IR), IGF-IIR, and myostatin (44 patients) was performed. Serum and muscle IGF-I and IGF-II, serum proinflammatory cytokines, and leg muscle strength, power, and fatigability were measured. Maintenance hemodialysis patients displayed significantly reduced mRNA levels for IGF-IEa mRNA (P < 0.05), IGF-II (P < 0.001), and IGF-IR (P < 0.001), and no difference in mRNAs for IGF-IEc, IGF-IIR, or myostatin as compared to normal controls. Muscle mRNA levels, in general, followed the same pattern in male and female maintenance hemodialysis patients considered separately. In the maintenance hemodialysis patients, muscle IGF-I protein, serum IGF-II and tumor necrosis factor-alpha (TNF-alpha) were each increased, whereas serum C-reactive protein (CRP) and interleukin-6 (IL-6) were normal. Muscle strength and power, but not fatigability, were reduced in the maintenance hemodialysis patients. In sedentary, clinically stable maintenance hemodialysis patients as compared to sedentary normal individuals, the mRNA levels for IGF-IEa, IGF-II, and the IGF-I receptor are decreased in vastus lateralis muscle. Protein levels for muscle IGF-I and serum IGF-II are increased.