Insulin-like growth factors (IGF) and IGF binding proteins in children with chronic renal failure.
The pathomechanism of growth retardation and catabolism in children with chronic renal failure (CRF) is multifactorial. Recent evidence indicates that in particular disturbances of the somatotropic hormone axis play an important pathogenic role. In preterminal CRF serum insulin-like growth factor (IGF)-I and IGF-II levels are normal, while in end-stage renal disease (ESRD), IGF-I levels are slightly decreased and IGF-II levels slightly increased. In view of the prevailing elevated growth hormone levels in ESRD, these serum IGF-I levels appear as inadequately low. Indeed, there is both clinical and experimental evidence for a decreased hepatic IGF-I production rate in CRF. This hepatic insensitivity to the action of GH is partially owing to a reduced GH receptor expression. The action and metabolism of IGFs are modulated by specific high-affinity IGF binding proteins (IGFBPs), which bind approximately 99% of circulating IGF. IGFBP-1, IGFBP-2, and low molecular weight IGFBP-3 fragments are increased in CRF serum in relation to the degree of renal dysfunction. Both decreased renal filtration, in particular of low molecular weight IGFBP-3 fragments, and increased hepatic production of IGFBP-1 and -2 contribute to high IGFBP serum levels. Experimental and clinical evidence suggests that these excessive high-affinity IGFBPs in CRF serum inhibit IGF action on target tissues by competition with the type 1 IGF receptor for IGF binding.
Tönshoff
B
B
University Children's Hospital, Heidelberg, Germany. Burkhard_Toenshoff@krzmail.krz.uni-heidelberg.de
Blum
W F
WF
Mehls
O
O
D002648:Child; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II