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Insulin-Like Growth Factor-Binding Protein-6 Levels Are Elevated in Serum of Children with Chronic Renal Failure: A Report of the Southwest Pediatric Nephrology Study Group¹

Baylor College of Medicine (D.R.P., S.K.D., E.D.B., P.D.K.L.), Houston, Texas 77030; Stanford University Medical School (F.L., B.K.B., R.L.H.), Stanford, California 94305; Genentech (J.W.F.), South San Francisco, California 94080; University Children’s Hospital (B.T., O.M.), Heidelberg, Germany; University Children’s Hospital (A.-M.W.), Tubingen, Germany; University of Washington (S.L.W.), Seattle, Washington 98108; and Columbia Hospital at Medical City (R.J.H.), Dallas, Texas 75230

Address all correspondence and requests for reprints to: Dr. David R. Powell, Texas Children’s Hospital, Clinical Care Center, MC# 3–2482, 6621 Fannin, Houston, Texas 77030. E-mail: dpowell{at}bcm.tmc.edu

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse 24- to 28-kDa IGFBP band identified by [¹²⁵I]IGF ligand blot. The present studies characterized this diffuse 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [¹²⁵I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [¹²⁵I]IGF-II but not [¹²⁵I]IGF-I, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 ± 1.7 nmol/L in 10 normal prepubertal children, 21.4 ± 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 ± 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 ± 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

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