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.

UNLABELLED: 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.

[Oxidative stress and hypertensive arteriopathy in children with primary hypertension--preliminary results]. / Stres oksydacyjny a uszkodzenie tetnic u dzieci z nadcisnieniem tetniczym pierwotnym--wyniki wstepne.

UNLABELLED: Hypertensive arteriopathy and intima-media (IMT) thickening is observed already in adolescents with primary hypertension (PH) at diagnosis. The injury of arterial wall may cause also generation of free radicals and free radicals may by itself perpetuate arterial wall injury. The aim of the study was to verify the hypothesis that children with PH are exposed to oxidative injury (Sox) due to impaired antioxidant barrier, and that markers of Sox correlate with IMT and metabolic risk factors of arteriosclerosis. STUDY DESIGN: controlled, cross-sectional. PATIENTS: 76 children with untreated PH, aged 14.7 yrs (5-20): 23 girls, 53 boys. CONTROLS: 83 healthy children aged 13.4 yrs (4-23): 44 girls, 39 boys. METHODS: Sono-graphic assessment of IMT in common carotid (cIMT) and superficial femoral arteries (cIMT). Sox was assessed as thiobarbituric acid reactive substances plasma concentration (TBARS), glutathione plasma concentration (GSH) as well as, glutathione peroxidase activity (GPX) were tested to demonstrate free radical scavenger activity. RESULTS: PH pts had greater cIMT (p<0.0001), carotid wall cross sectional area (WCSA) (p<0.0001), fIMT (p<0.0001), lower HDL-cholesterol, apoA1/apoB than control group (p<0.05). GSH and GPX did not differ between groups but TBARS was significantly greater in PH pts (p <0.05). In control group fIMT significantly correlated with hCRP (r=0.30, p<0.01), homocysteine (r=0.3, p< 0.05), apoA1 (r=-0.2417, p<0.05), TBARS (r=0.329, p<0.01), GPX (r=-0.241, p<0.05) and with GSH (r=-0.22, p=0.05). In pts group, there were similar correlations between fIMT and hCRP (r=0.29, p<0.05), apoA1/apoB (r=-0.28, p<0.05). CONCLUSIONS: PH pts are exposed to significantly higher Sox than controls. The significant correlations between markers of Sox and biochemical parameters suggest that hypertensive arteriopathy is an effect of complex interplay between Sox, metabolic and hemodynamic insults.

[Voiding dysfunction in children with vesicoureteral reflux]. / Zaburzenia funkcji pecherza moczowego u dzieci z odplywami pecherzowo-moczowodowymi.

UNLABELLED: The aim of the study was to assess the rate of development of voiding dysfunction (VD) in patients with reflux nephropathy. We investigated 150 pts with vesicoureteral reflux (VUR): 33 boys and 117 girls in mean age 9 +/- 3.3 years with normal renal function. In all pts we performed renal scintigraphy (DMSA) and ABPM. Renal scarring by DMSA scan was categorized into grades 1-4. In all pts we assessed high and laterality of VUR, renal function (clearance creatinine--Ccr) and occurency of hypertension (HT). RESULTS: Of 150 pts, 80 (53.3%) developed VD (54.5% boys and 52% girls). DMSA grade: 1--27 pts, 2--85 pts; 3--31 pts; 4--7 pts. No statistically significant difference was found depends of: sex, age, laterality of renal damage in DMSA, unilateral and bilateral reflux for the development of VD. The incidence 3-4 grade in DMSA scan was significantly higher in pts with IV-V grade of VUR in comparison to pts with lower grade of VUR in group with and without voiding dysfunction. IV-V grades of VUR were observed more frequently in pts with bladder/sphincter dysfunction. The occurency of HT in group with VD and without VD was 12 pts (15%) and 8 (11.4%) respectively (ns). Pts with VD have lower Ccr in comparison with pts without VD (129.1 vs 136.3 ml/min/1.73 m2; p<0.05). CONCLUSIONS: Approximately 50% of patients with VUR demonstrated VD. VD occurred independent of age. IV-V degrees VUR and more severe changes in DMSA scan were seen in pts with bladder/sphincter dysfunction.