NDT Advance Access originally published online on September 26, 2007
Nephrology Dialysis Transplantation 2007 22(12):3487-3494; doi:10.1093/ndt/gfm300
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Urinary excretion of endothelin-1 (ET-1), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF165) in paediatric chronic kidney diseases: results of the ESCAPE trial
aw Litwin1
ladowska1
1Department of Nephrology, Kidney Transplantation and Hypertension, Children's Memorial Health Institute, Warsaw, Poland, 2Division of Pediatric Nephrology, Hospital for Pediatric and Adolescent Medicine, University of Heidelberg, Germany, 3Department of Radioimmunology, Children's Memorial Health Institute, Warsaw, Poland, 4Department of Pediatrics, Medical University Vienna, Austria, 5Karolinska Institute, Department of Pediatrics, Huddinge University Hospital, Sweden, 6Serviçio de Pediatria, Hospital de S. João, Porto, Portugal, 7CHU Hopital de Hautepierre, Service de Pédiatrie 3, Strasbourg, France and 8First Department of Pediatrics, Semmelweis University, Budapest, Hungary
Correspondence and offprint requests to: Ryszard Grenda, Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland. Email: r.grenda{at}czd.pl
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Abstract |
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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 VEGF165 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.
Keywords: adolescents; children; chronic kidney disease; ET-1; TGF-β1; urinary biomarkers excretion; VEGF165
Members of the ESCAPE Trial Group are listed in the appendix.