Growth hormone in renal transplantation--the mode of action, animal studies, and clinical use.
During circulation, growth hormone (GH) is bound to about 50% by the high-affinity, low-capacity GH-binding protein (BP). GHBP represents the extracellular binding domain of the GH receptor and modulates the action of GH. After binding to its receptor, GH induces the local production of insulin-like growth factor 1 (IGF-1) by autocrine and paracrine mechanisms. In uremia, the plasma GH-binding activity is low and does not get up-regulated by recombinant human GH treatment, which is in contrast to the experience in short, normal children. There is evidence that hepatic IGF-1 production is low, whereas the serum concentration of IGF-binding protein 3 (IGF-BP3) and other IGFBPs is increased because of the reduced renal clearance of the low-molecular-weight fragment of IGF-BP. This result in the reduced bioavailability of free IGF-1 and reduced IGF bioactivity. There is a strong interaction between GH and corticosteroids. Corticosteroids suppress growth by reducing the food efficiency ratio (weight gain per food intake), reduce pituitary GH secretion, and decrease the local production of and cell responsiveness for IGF-1. The growth-depressing and catabolic effects of corticosteroids can be counterbalanced dose dependently by recombinant human GH in animal experiments, and growth can be improved in corticosteroid-treated renal allograft recipients with and without normal renal function. It is not clear at this time to what extent GH may induce acute or chronic rejection crises.
Mehls
O
O
Division of Pediatric Nephrology, University Children's Hospital of Heidelberg, Germany.
Tönshoff
B
B
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000818:Animals; D002648:Child; D004351:Drug Resistance; D006084:Graft Rejection / Q000187:drug effects; D006130:Growth Disorders / Q000209:etiology / Q000517:prevention & control*; D013006:Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016030:Kidney Transplantation; D007938:Leukemia / Q000139:chemically induced; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control*; D011627:Puberty / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D014511:Uremia / Q000150:complications / Q000503:physiopathology / Q000601:surgery
D000305:Adrenal Cortex Hormones; D011994:Recombinant Proteins; D013006:Growth Hormone