IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH.
OBJECTIVE
Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH.


METHODS
Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot.


RESULTS
Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment.


CONCLUSIONS
There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.
Department of Medicine, National University of Singapore, Singapore 119074.
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X
Zhou
K Y
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Loke
C C
CC
Pillai
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HK
How
H K
HK
Yap
K O
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Lee
D000293:Adolescent; D015153:Blotting, Western; D001827:Body Height / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism / Q000652:urine; D002648:Child; D002784:Cholesterol / Q000097:blood; D004392:Dwarfism / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism / Q000652:urine; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000378:metabolism / Q000652:urine; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism / Q000652:urine; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008024:Ligands; D008297:Male; D016555:Matched-Pair Analysis; D009401:Nephrosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000652:urine; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013002:Somatomedins / Q000378:metabolism*; D013577:Syndrome
D002352:Carrier Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D008024:Ligands; D013002:Somatomedins; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D002784:Cholesterol; D011239:Prednisolone