Urinary excretion of endothelin-1 (ET-1), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF 165) in paediatric chronic kidney diseases: Results of the ESCAPE trial

Ryszard Grenda, Elke Wühl, Mieczysław Litwin, Roman Janas, Joanna Śladowska, Klaus Arbeiter, Ulla Berg, Alberto Caldas-Afonso, Michel Fischbach, Otto Mehls, P. Sallay, Franz Schaefer

Research output: Contribution to journalArticle

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Abstract

The severity and dynamics of renal tissue damage in chronic kidney disease (CKD) may be reflected by the urinary excretion of vasoactive and growth factors released by the damaged kidney. Urinary excretion of ET-1, TGF-β1 and VEGF165 was evaluated in 303 children with CKD stage II-IV (GFR 48 ± 22 ml/min/1.73 m2) and 81 age-matched healthy controls. Major renal disease groups were hypo-/dysplastic kidney disease (N = 183), obstructive uropathies (N = 47), glomerulopathies (N = 34), nephronophthisis (N = 19) and polycystic kidney disease (N = 20). Results. The mean urinary excretion rates of each of the three putative biomarkers were significantly elevated in CKD patients compared to controls: 965 ± 2042 vs 216 ± 335 fmol/g creatinine for ET-1; 252 ± 338 vs 155 ± 158 ng/g for VEGF; 31.6 ± 37.0 vs 10.9 ± 9.8 ng/g for TGF-β1 (each P <0.0001). The excretion of ET-1 and TGF-β1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-β1 and VEGF excretion rates were inversely correlated with age (r = -0.22, -0.32 and -0.17, all P <0.005) and renal function (r = -0.21, -0.13 and -0.15; P <0.001; <0.05; <0.01; respectively) VEGF and TGF-β1 excretion rates were positively correlated both in patients and controls. Conclusions. Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-β1 and VEGF 165 in comparison to healthy children. Urinary excretion of these biomarkers was most enhanced in patients with obstructive uropathies. A positive correlation between urinary TGF-β1 and VEGF165 excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.

Original languageEnglish
Pages (from-to)3487-3494
Number of pages8
JournalNephrology Dialysis Transplantation
Volume22
Issue number12
DOIs
Publication statusPublished - Dec 2007

Fingerprint

Transforming Growth Factors
Endothelin-1
Chronic Renal Insufficiency
Pediatrics
Vascular Endothelial Growth Factor A
Kidney
Biomarkers
Polycystic Kidney Diseases
Kidney Diseases
human VEGFA protein
Creatinine
Intercellular Signaling Peptides and Proteins

Keywords

  • Adolescents
  • Children
  • Chronic kidney disease
  • ET-1
  • TGF-β1
  • Urinary biomarkers excretion
  • VEGF

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Urinary excretion of endothelin-1 (ET-1), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF 165) in paediatric chronic kidney diseases : Results of the ESCAPE trial. / Grenda, Ryszard; Wühl, Elke; Litwin, Mieczysław; Janas, Roman; Śladowska, Joanna; Arbeiter, Klaus; Berg, Ulla; Caldas-Afonso, Alberto; Fischbach, Michel; Mehls, Otto; Sallay, P.; Schaefer, Franz.

In: Nephrology Dialysis Transplantation, Vol. 22, No. 12, 12.2007, p. 3487-3494.

Research output: Contribution to journalArticle

Grenda, Ryszard ; Wühl, Elke ; Litwin, Mieczysław ; Janas, Roman ; Śladowska, Joanna ; Arbeiter, Klaus ; Berg, Ulla ; Caldas-Afonso, Alberto ; Fischbach, Michel ; Mehls, Otto ; Sallay, P. ; Schaefer, Franz. / Urinary excretion of endothelin-1 (ET-1), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF 165) in paediatric chronic kidney diseases : Results of the ESCAPE trial. In: Nephrology Dialysis Transplantation. 2007 ; Vol. 22, No. 12. pp. 3487-3494.
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abstract = "The severity and dynamics of renal tissue damage in chronic kidney disease (CKD) may be reflected by the urinary excretion of vasoactive and growth factors released by the damaged kidney. Urinary excretion of ET-1, TGF-β1 and VEGF165 was evaluated in 303 children with CKD stage II-IV (GFR 48 ± 22 ml/min/1.73 m2) and 81 age-matched healthy controls. Major renal disease groups were hypo-/dysplastic kidney disease (N = 183), obstructive uropathies (N = 47), glomerulopathies (N = 34), nephronophthisis (N = 19) and polycystic kidney disease (N = 20). Results. The mean urinary excretion rates of each of the three putative biomarkers were significantly elevated in CKD patients compared to controls: 965 ± 2042 vs 216 ± 335 fmol/g creatinine for ET-1; 252 ± 338 vs 155 ± 158 ng/g for VEGF; 31.6 ± 37.0 vs 10.9 ± 9.8 ng/g for TGF-β1 (each P <0.0001). The excretion of ET-1 and TGF-β1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-β1 and VEGF excretion rates were inversely correlated with age (r = -0.22, -0.32 and -0.17, all P <0.005) and renal function (r = -0.21, -0.13 and -0.15; P <0.001; <0.05; <0.01; respectively) VEGF and TGF-β1 excretion rates were positively correlated both in patients and controls. Conclusions. Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-β1 and VEGF 165 in comparison to healthy children. Urinary excretion of these biomarkers was most enhanced in patients with obstructive uropathies. A positive correlation between urinary TGF-β1 and VEGF165 excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.",
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AU - Grenda, Ryszard

AU - Wühl, Elke

AU - Litwin, Mieczysław

AU - Janas, Roman

AU - Śladowska, Joanna

AU - Arbeiter, Klaus

AU - Berg, Ulla

AU - Caldas-Afonso, Alberto

AU - Fischbach, Michel

AU - Mehls, Otto

AU - Sallay, P.

AU - Schaefer, Franz

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N2 - The severity and dynamics of renal tissue damage in chronic kidney disease (CKD) may be reflected by the urinary excretion of vasoactive and growth factors released by the damaged kidney. Urinary excretion of ET-1, TGF-β1 and VEGF165 was evaluated in 303 children with CKD stage II-IV (GFR 48 ± 22 ml/min/1.73 m2) and 81 age-matched healthy controls. Major renal disease groups were hypo-/dysplastic kidney disease (N = 183), obstructive uropathies (N = 47), glomerulopathies (N = 34), nephronophthisis (N = 19) and polycystic kidney disease (N = 20). Results. The mean urinary excretion rates of each of the three putative biomarkers were significantly elevated in CKD patients compared to controls: 965 ± 2042 vs 216 ± 335 fmol/g creatinine for ET-1; 252 ± 338 vs 155 ± 158 ng/g for VEGF; 31.6 ± 37.0 vs 10.9 ± 9.8 ng/g for TGF-β1 (each P <0.0001). The excretion of ET-1 and TGF-β1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-β1 and VEGF excretion rates were inversely correlated with age (r = -0.22, -0.32 and -0.17, all P <0.005) and renal function (r = -0.21, -0.13 and -0.15; P <0.001; <0.05; <0.01; respectively) VEGF and TGF-β1 excretion rates were positively correlated both in patients and controls. Conclusions. Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-β1 and VEGF 165 in comparison to healthy children. Urinary excretion of these biomarkers was most enhanced in patients with obstructive uropathies. A positive correlation between urinary TGF-β1 and VEGF165 excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.

AB - The severity and dynamics of renal tissue damage in chronic kidney disease (CKD) may be reflected by the urinary excretion of vasoactive and growth factors released by the damaged kidney. Urinary excretion of ET-1, TGF-β1 and VEGF165 was evaluated in 303 children with CKD stage II-IV (GFR 48 ± 22 ml/min/1.73 m2) and 81 age-matched healthy controls. Major renal disease groups were hypo-/dysplastic kidney disease (N = 183), obstructive uropathies (N = 47), glomerulopathies (N = 34), nephronophthisis (N = 19) and polycystic kidney disease (N = 20). Results. The mean urinary excretion rates of each of the three putative biomarkers were significantly elevated in CKD patients compared to controls: 965 ± 2042 vs 216 ± 335 fmol/g creatinine for ET-1; 252 ± 338 vs 155 ± 158 ng/g for VEGF; 31.6 ± 37.0 vs 10.9 ± 9.8 ng/g for TGF-β1 (each P <0.0001). The excretion of ET-1 and TGF-β1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-β1 and VEGF excretion rates were inversely correlated with age (r = -0.22, -0.32 and -0.17, all P <0.005) and renal function (r = -0.21, -0.13 and -0.15; P <0.001; <0.05; <0.01; respectively) VEGF and TGF-β1 excretion rates were positively correlated both in patients and controls. Conclusions. Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-β1 and VEGF 165 in comparison to healthy children. Urinary excretion of these biomarkers was most enhanced in patients with obstructive uropathies. A positive correlation between urinary TGF-β1 and VEGF165 excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.

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