Effects of uremia and inflammation on growth hormone resistance in patients with chronic kidney diseases.
Resistance to the anabolic action of growth hormone may contribute to the loss of strength and muscle mass in adult patients with chronic kidney disease. We tested this hypothesis by infusing growth hormone in patients to levels necessary to saturate hormone receptors. This led to a significant decrease of plasma potassium and amino acid levels in control and hyperkalemic patients with chronic kidney disease. These effects were completely or partially blunted in patients with elevated C-reactive protein levels. In forearm perfusion studies, growth hormone caused a further decrease in the negative potassium and protein balance of hemodialysis patients without inflammation but no effect was seen in patients with inflammation. Only IL-6 levels and age were found to be independent correlates in these growth hormone-induced variations in plasma potassium and blood amino acids. This shows that although a resistance to pharmacologic doses of growth hormone is not a general feature of patients with chronic kidney disease, there is a subgroup characterized by blunted growth hormone action. Our results support the hypothesis that uremia with inflammation, but not uremia per se, inhibits downstream growth hormone signaling contributing to muscle atrophy.
Garibotto
Giacomo
G
Division of Nephrology, Department of Internal Medicine, Genoa, Italy. gari@unige.it
Russo
Rodolfo
R
Sofia
Antonella
A
Ferone
Diego
D
Fiorini
Fulvio
F
Cappelli
Valeria
V
Tarroni
Alice
A
Gandolfo
Maria Teresa
MT
Vigo
Emanuela
E
Valli
Alessandro
A
Arvigo
Marica
M
Verzola
Daniela
D
Ravera
Giovanbattista
G
Minuto
Francesco
F
D000367:Age Factors; D000368:Aged; D000596:Amino Acids / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D004351:Drug Resistance; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D007674:Kidney Diseases / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009133:Muscular Atrophy / Q000209:etiology; D011188:Potassium / Q000097:blood; D014511:Uremia
D000596:Amino Acids; D015850:Interleukin-6; D019382:Human Growth Hormone; D011188:Potassium