The insulin-like growth factor axis and growth in children with chronic renal failure: A report of the southwest pediatric nephrology study group

David R. Powell, Susan K. Durham, Frances Liu, Bonita K. Baker, Phillip Lee, Sandra L. Watkins, Phil G. Campbell, Eileen D. Brewer, Raymond L. Hintz, Ronald J. Hogg

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Children with chronic renal failure (CRF) are often growth retarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35- kDa fractions of CRF serum contribute to CRF growth failure This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP- 3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150- kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.

Original languageEnglish (US)
Pages (from-to)1654-1661
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number5
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 3
Pediatrics
Nephrology
Somatomedins
Chronic Kidney Failure
Insulin-Like Growth Factor Binding Proteins
Growth
Serum
Proteolysis
Size exclusion chromatography
Chromatography
Stoichiometry
Gel Chromatography

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

The insulin-like growth factor axis and growth in children with chronic renal failure : A report of the southwest pediatric nephrology study group. / Powell, David R.; Durham, Susan K.; Liu, Frances; Baker, Bonita K.; Lee, Phillip; Watkins, Sandra L.; Campbell, Phil G.; Brewer, Eileen D.; Hintz, Raymond L.; Hogg, Ronald J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 5, 1998, p. 1654-1661.

Research output: Contribution to journalArticle

Powell, David R. ; Durham, Susan K. ; Liu, Frances ; Baker, Bonita K. ; Lee, Phillip ; Watkins, Sandra L. ; Campbell, Phil G. ; Brewer, Eileen D. ; Hintz, Raymond L. ; Hogg, Ronald J. / The insulin-like growth factor axis and growth in children with chronic renal failure : A report of the southwest pediatric nephrology study group. In: Journal of Clinical Endocrinology and Metabolism. 1998 ; Vol. 83, No. 5. pp. 1654-1661.
@article{8a6e3230be224a7d8bb5d380cd019644,
title = "The insulin-like growth factor axis and growth in children with chronic renal failure: A report of the southwest pediatric nephrology study group",
abstract = "Children with chronic renal failure (CRF) are often growth retarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35- kDa fractions of CRF serum contribute to CRF growth failure This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP- 3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150- kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.",
author = "Powell, {David R.} and Durham, {Susan K.} and Frances Liu and Baker, {Bonita K.} and Phillip Lee and Watkins, {Sandra L.} and Campbell, {Phil G.} and Brewer, {Eileen D.} and Hintz, {Raymond L.} and Hogg, {Ronald J.}",
year = "1998",
doi = "10.1210/jc.83.5.1654",
language = "English (US)",
volume = "83",
pages = "1654--1661",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "5",

}

TY - JOUR

T1 - The insulin-like growth factor axis and growth in children with chronic renal failure

T2 - A report of the southwest pediatric nephrology study group

AU - Powell, David R.

AU - Durham, Susan K.

AU - Liu, Frances

AU - Baker, Bonita K.

AU - Lee, Phillip

AU - Watkins, Sandra L.

AU - Campbell, Phil G.

AU - Brewer, Eileen D.

AU - Hintz, Raymond L.

AU - Hogg, Ronald J.

PY - 1998

Y1 - 1998

N2 - Children with chronic renal failure (CRF) are often growth retarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35- kDa fractions of CRF serum contribute to CRF growth failure This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP- 3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150- kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.

AB - Children with chronic renal failure (CRF) are often growth retarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35- kDa fractions of CRF serum contribute to CRF growth failure This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP- 3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150- kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.

UR - http://www.scopus.com/inward/record.url?scp=7844235112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7844235112&partnerID=8YFLogxK

U2 - 10.1210/jc.83.5.1654

DO - 10.1210/jc.83.5.1654

M3 - Article

C2 - 9589673

AN - SCOPUS:7844235112

VL - 83

SP - 1654

EP - 1661

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 5

ER -