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), despi te being in remission on glucocorticoids, continue to have growth retardati on and short stature. The mechanism is uncertain as both chronic glucocorti costeroids and the nephrotic syndrome may independently affect growth. We i nvestigated 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. Design and 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 ag e = 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, o ne matched for bone age (CBA; mean bone age = 9.2 years), and another for c hronological age (CCA; mean chronological age = 13 years). Subsequently, th ree 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 bot h control groups; but serum IGFBP-3 did not differ significantly Urinary IG FBP-2, IGFBP-3 and ALS were detectable in the SDNS children only, With GH t reatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compar ed with pre-treatment values, and returned to baseline after cessation of G H treatment. Urinary IGFBPs did not change significantly with GH treatment. Conclusions: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS i n children with SDNS in remission with growth retardation. However, the sig nificant elevation in serum IGF-I suggests that glucocorticoid-induced resi stance to IGF is the main factor responsible for the persistent growth reta rdation in these children. Exogenous GH was able to overcome this resistanc e by further increasing serum IGF-I.