IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH

Abstract

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. Design and Methods: Total and`free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age 12X6 years; mean bone age 9X1 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 9X2 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.

Effects of Oral Sodium Bicarbonate in Patients with CKD

“…The reduction in serum IGF-1 could indicate amelioration of an IGF-1 signaling defect in skeletal muscle (10,26). Alternatively, the increase in IGFBP-1 could stimulate IGF-1 action at the cellular level, despite lower serum IGF-1 (27,28).…”

Long-term results of children diagnosed with idiopathic nephrotic syndrome; single center experience

“…In patients with steroid-dependent NS, growth hormone treatment has been found to increase the level of insulin like growth factor-1 (32). In the literature, it was reported that an adolescent patient with short stature who was diagnosed with steroid-dependent NS was treated successfully with recombinant human growth hormone during usage of cyclosporine (33).…”

Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study

“…However, this is in line with earlier reports describing an association between glucocorticoid use and increased serum IGF-1. (41)(42)(43)(44)(45) The IGF-1-related detrimental effects of glucocorticoid treatment on bone therefore rather may be the result of IGF-1 resistance and/or reduced local IGF-1 expression in osteoblasts. (41,42,(44)(45)(46)(47) Adjustment for glucocorticoid treatment did not alter the association between low serum IGF-1 and increased risk of fractures observed in this study.…”