Urinary excretion of endothelin-1 (ET-1), transforming growth factor- beta1 (TGF- beta1) and vascular endothelial growth factor (VEGF165) in paediatric chronic kidney diseases: results of the ESCAPE trial.
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-beta1 and VEGF(165) was evaluated in 303 children with CKD stage II-IV (GFR 48 +/- 22 ml/min/1.73 m(2)) 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-beta1 (each P < 0.0001). The excretion of ET-1 and TGF-beta1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-beta1 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-beta1 excretion rates were positively correlated both in patients and controls.


CONCLUSIONS
Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-beta1 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-beta1 and VEGF(165) excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.
Grenda
Ryszard
R
Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland. r.grenda@czd.pl
Wühl
Elke
E
Litwin
Mieczyslaw
M
Janas
Roman
R
Sladowska
Joanna
J
Arbeiter
Klaus
K
Berg
Ulla
U
Caldas-Afonso
Alberto
A
Fischbach
Michel
M
Mehls
Otto
O
Sallay
Peter
P
Schaefer
Franz
F
D002648:Child; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D019332:Endothelin-1 / Q000652:urine*; D006801:Humans; D007674:Kidney Diseases / Q000652:urine*; D053773:Transforming Growth Factor beta1 / Q000652:urine*; D042461:Vascular Endothelial Growth Factor A / Q000652:urine*
D019332:Endothelin-1; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A