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18

28

TH

CONGRESS OF THE ESPU

14:30–14:33

S1-14 (PP)

URINE PROTEOMICS IN CHILDREN

WITH VESICOURETERAL REFLUX

Anja WEINHANDL

1

, Suzann BAUMANN

1

, Dagmar CSAICSICH

2

, Karin SCHLANGEN

3

,

Martin METZELDER

4

, Goran MITULOVIC

5

and Alexander SPRINGER

6

1) Medical University Vienna, Pediatric Urology, Vienna, AUSTRIA - 2) Medical University Vienna, Department

of Pediatrics, Vienna, AUSTRIA - 3) Medical University Vienna, Center for Medical Statistics, Vienna, AUSTRIA -

4) Medical University Vienna, Department of Pediatric Surgery, Vienna, AUSTRIA - 5) Medical University Vienna, Head

of Proteomics Core Facility, Vienna, AUSTRIA - 6) Medical University Vienna, Paediatric Urology, Vienna, AUSTRIA

PURPOSE

Children with vesicoureteral reflux (VUR) are at risk for renal damage. Currently, the detection of

VUR and associated renal scaring in children is invasive, expensive and associated with radiation

burden. Noninvasive methods such as urinary protein analysis would greatly facilitate management

of VUR.

MATERIAL AND METHODS

Between 2012 and 2014 urinary samples from 16 VUR patients (5 low grade VUR, 5 with renal

dysplasia/reflux nephropathy. 7 girls, 7 children < 12 months) and 10 controls (non-urologic hospital

admittance) were collected. Samples were centrifuged at 3500rpm for 15min and supernatants were

collected and frozen at -80°C for further processing. Urine proteomics was performed using a stand-

ard protocol (Data Analysis 4.1, Mascot 2.4.1, ProteinScape 3.1). In order to identify differentially

expressed proteins the t-test was used (significance set at p <0.05). Biostatistical techniques were

used to describe distinct protein expression profiles for VUR. Protein-protein interaction information

was extracted from publicly available repositories (Gene ontology, PANTHER, Process networks).

RESULTS

For VUR vs. controls 61 proteins were significantly expressed, amongst them several key proteins

could be identified (Cadherin-15, IGFBP2, Uroplakin-2, Aquaporin-2 and Metalloproteinase 16). For

low grade vs. severe VUR there were 42 proteins significantly expressed, but no well-known key

proteins. In dysplastic kidneys/nephropathy vs. controls 56 proteins were significantly expressed

including classical stress response proteins (Heat shock 70 (HSP-70-1, HSP90-a, HSPb-1, HSC71,

HSP70-2). Distinct VUR proteome expression could be allocated to biological processes and path-

ways (cell cycle, apoptosis, biological regulation, cell adhesion, etc.).

CONCLUSIONS

Using an exploratory, proteome-wide approach and bioinformatics analysis, we could identify

a distinct VUR typical expression profile. The nature of VUR is diverse, therefore we observed

inter-individual variance. Further prospective studies are warranted to test if proteomic findings will

have an impact as non-invasive prognostic marker in the management of VUR.

14:33–14:55

Discussion