Insulin-like growth factor binding protein-3 protease activity in the urine of children with chronic renal failure

Dae Yeol Lee, Pinchas Cohen, Alan M. Krensky, Ronald (Ron) Rosenfeld, Peter D. Yorgin

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The insulin-like growth factors, IGF-1 and IGF-II, are polypeptides that potentiate cellular growth. In addition to binding to specific cell surface receptors, the IGFs bind with high affinity to a family of proteins, the insulin-like growth factor binding proteins (IGFBPs). Serum and urine IGFBP patterns are altered in individuals with chronic renal failure (CRF). We recently reported that the urinary IGFBP pattern of CRF patients is unique for increased insulin-like growth factor binding protein-1 (U-IGFBP-1) levels. In this study, we used western ligand blotting (WLB), western immunoblotting (WIB), and radioimmunoassay (RIA) to further evaluate serum and urine IGFBP profiles of children with CRF (n=14). Five patients with CRF displayed decreased serum IGFBP-3 profiles by WLB. Serum IGFBP-3 WIB profiles were remarkable for 30- and 20-kDa fragments of IGFBP-3 not seen in control serum. Serum IGFBP-3 levels, as determined by RIA, were slightly elevated. Serum levels of IGFBP-2 also were increased, although not at a level reaching statistical significance. WLB of CRF urine revealed a large increase in U-IGFBP-1 and a complete absence of urinary IGFBP-3. Recent studies of serum from pregnant women and seminal plasma have demonstrated a similar absence of intact IGFBP-3, due to the presence of a specific IGFBP-3 protease. To evaluate whether an IGFBP-3 protease accounts for the absence of intact U-IGFBP-3 in children with CRF, urine and serum samples from individuals with CRF and controls were tested. An IGFBP-3 protease assay using concentrated urine revealed the presence of two distinct proteases found only in the CRF urines. Serum IGFBP-3 protease activity was no greater in patients with CRF than in controls. We conclude that the decrease in intact urinary IGFBP-3 is due to proteolysis by an IGFBP-3 protease.

Original languageEnglish (US)
Pages (from-to)416-423
Number of pages8
JournalPediatric Nephrology
Volume7
Issue number4
DOIs
StatePublished - Aug 1993
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 3
Chronic Kidney Failure
Urine
Insulin-Like Growth Factor Binding Proteins
Serum
Western Blotting
Insulin-Like Growth Factor Binding Protein 1
Ligands
Radioimmunoassay
insulin-like growth factor binding protein-3 protease
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor II
Cell Surface Receptors
Somatomedins
Semen
Insulin-Like Growth Factor I
Proteolysis
Pregnant Women
Peptide Hydrolases
Peptides

Keywords

  • Chronic renal failure
  • Insulin-like growth factor binding protein-3 protease
  • Insulin-like growth factor binding proteins
  • Urine

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

Insulin-like growth factor binding protein-3 protease activity in the urine of children with chronic renal failure. / Lee, Dae Yeol; Cohen, Pinchas; Krensky, Alan M.; Rosenfeld, Ronald (Ron); Yorgin, Peter D.

In: Pediatric Nephrology, Vol. 7, No. 4, 08.1993, p. 416-423.

Research output: Contribution to journalArticle

Lee, Dae Yeol ; Cohen, Pinchas ; Krensky, Alan M. ; Rosenfeld, Ronald (Ron) ; Yorgin, Peter D. / Insulin-like growth factor binding protein-3 protease activity in the urine of children with chronic renal failure. In: Pediatric Nephrology. 1993 ; Vol. 7, No. 4. pp. 416-423.
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abstract = "The insulin-like growth factors, IGF-1 and IGF-II, are polypeptides that potentiate cellular growth. In addition to binding to specific cell surface receptors, the IGFs bind with high affinity to a family of proteins, the insulin-like growth factor binding proteins (IGFBPs). Serum and urine IGFBP patterns are altered in individuals with chronic renal failure (CRF). We recently reported that the urinary IGFBP pattern of CRF patients is unique for increased insulin-like growth factor binding protein-1 (U-IGFBP-1) levels. In this study, we used western ligand blotting (WLB), western immunoblotting (WIB), and radioimmunoassay (RIA) to further evaluate serum and urine IGFBP profiles of children with CRF (n=14). Five patients with CRF displayed decreased serum IGFBP-3 profiles by WLB. Serum IGFBP-3 WIB profiles were remarkable for 30- and 20-kDa fragments of IGFBP-3 not seen in control serum. Serum IGFBP-3 levels, as determined by RIA, were slightly elevated. Serum levels of IGFBP-2 also were increased, although not at a level reaching statistical significance. WLB of CRF urine revealed a large increase in U-IGFBP-1 and a complete absence of urinary IGFBP-3. Recent studies of serum from pregnant women and seminal plasma have demonstrated a similar absence of intact IGFBP-3, due to the presence of a specific IGFBP-3 protease. To evaluate whether an IGFBP-3 protease accounts for the absence of intact U-IGFBP-3 in children with CRF, urine and serum samples from individuals with CRF and controls were tested. An IGFBP-3 protease assay using concentrated urine revealed the presence of two distinct proteases found only in the CRF urines. Serum IGFBP-3 protease activity was no greater in patients with CRF than in controls. We conclude that the decrease in intact urinary IGFBP-3 is due to proteolysis by an IGFBP-3 protease.",
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