Insulin-like growth factor-I (IGF-I) and IGF-binding proteins in children with nephrotic syndrome.

Abstract

Growth failure appears to be a major problem for nephrotic children who fail to respond to steroid therapy. Recently altered serum insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) profiles are reported in renal failure and glomerulonephritis. In this study, the serum IGFBP profile was evaluated by Western ligand blot and RIA in 22 patients with the nephrotic syndrome. Serum IGFBP-3 was decreased, whereas IGFBP-2 was increased in most patients with the nephrotic syndrome. The mean serum IGFBP-3 level was 2123 +/- 531 ng/mL in active states and was increased to a normal level (3593 +/- 407 ng/mL) in remission states. We also measured serum IGF-I by RIA. The serum concentration of IGF-I (mean +/- SD) was 67.4 +/- 23.2 ng/mL in active states and was increased to 127.1 +/- 21.8 ng/mL in remission states, but was still lower than that in control subjects (180.4 +/- 15.8 ng/mL). IGF-I and IGFBP-3 levels were not correlated with primary renal diseases or the amount of proteinuria. For serum IGF-IGFBP complexes, 150-kDa complexes were significantly decreased in patients with the nephrotic syndrome compared with those in control subjects. In urine from nephrotic syndrome patients, 150- and 50-kDa complexes were found, whereas these complexes did not exist in the urine of control subjects. We speculate that low serum IGF-I and IGFBP-3 levels would be partially due to the increased urinary losses of serum IGF-IGFBP complexes, especially that of 150 kDa, and these changes may contribute to growth failure in persistent nephrotic syndrome.

The Insulin-Like Growth Factor System in Kidney Diseases

“…IGFs were mainly excreted in the urine in the 45-kD molecular weight form, but IGFs in the 150-kD form also appeared in the urine of some nephrotics [38]. Similar results have been reported in nephrotic children [39]. In a recent study reported by Haffner et al [40], in nephrotic children, the serum immunoreactive IGFBP-3 levels were found to be elevated due to an increase in the low molecular weight IGFBP fragments, while there was a decrease in the 150-kD IGFBP ternary complex in the serum with an excess of low molecular weight IGFBPs.…”

Cardiac remodeling and dysfunction in nephrotic syndrome

“…Nevertheless, we cannot exclude a systemic disturbance of the growth hormone/IGF-1 axis, as increased renal excretion and reduced circulating levels of IGF-1 and IGFbinding proteins have been reported in the NS. 31,32 This disturbance might contribute to growth and development retardation described both in experimental models and in children with poorly controlled NS. 5,33 We did not observe growth retardation, as estimated by tibial length, in PANtreated rats.…”