Serum insulin-like growth factors and their binding proteins in children with end-stage renal disease.
Serum levels of insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 were measured in 54 children with end-stage renal disease (ESRD). The results were compared with their respective age-dependent normal ranges. IGFs and IGFBPs were quantified by specific radioimmunoassay. Serum IGF-I in children with ESRD tended to cluster in the low-normal range. Mean age-related serum IGF-I levels were slightly, but significantly decreased (-1.08 +/- 0.17 SDS). In view of the prevailing elevated growth hormone levels in ESRD, these serum IGF-I levels must be interpreted as inadequately low. In contrast to IGF-I, individual serum IGF-II levels were either in the upper-normal range or clearly elevated. Mean age-related IGF-II (1.09 +/- 0.15 SDS) was slightly, but significantly elevated. Mean age-related IGFBP-1 serum levels (2.20 +/- 0.10 SDS) were moderately increased, while mean age-related serum IGFBP-2 (5.65 +/- 0.36) and IGFBP-3 levels (3.60 +/- 0.19) were markedly elevated. Affinity cross-linking of 125iodine-IGF-II to sera from patients with ESRD and immunoprecipitation with a specific antiserum showed that low molecular weight IGFBP-3 fragments in ESRD serum are capable of binding IGF. In patients with ESRD, a rapid and persistent decline of immunoreactive IGFBP-3 in response to restoration of renal function by renal transplantation was observed. This finding indicates that renal dysfunction contributes to high immunoreactive IGFBP-3 levels in ESRD. In conclusion, the imbalance between normal total IGF levels and the excess of IGFBPs in ESRD is likely to play a role in growth failure in these children.
Tönshoff
B
B
Division of Pediatric Nephrology, University Children's Hospitals, Heidelberg, Germany.
Blum
W F
WF
Mehls
O
O
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007457:Iodine Radioisotopes; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D011863:Radioimmunoassay; D012016:Reference Values; 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; D007457:Iodine Radioisotopes; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II