Abstract Book - 26th ESPU Congress, Joint Meeting with ICCS + SPU + AAP/SOU + AAPU + SFU

14:10 - 14:13

S9-7

(PP)

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APOLIPOPROTEIN A-IV AND RENAL L-TYPE FATTY ACID BINDING PROTEIN:

NOVEL BIOMARKERS OF TUBULAR INJURY IN PEDIATRIC NEPHROLITHIASIS

Larisa KOVACEVIC

, Hong LU

, Joseph A. CARUSO

and Yegappan LAKSHMANAN

1) Children's Hospital of Michigan, Pediatric Urology, Detroit, USA - 2) Proteomic Center, Wayne State University,

Proteomics, Detroit, USA

PURPOSE

We assessed the differences in the urinary proteins between children with renal stones (RS), and healthy controls (HC),

with particular attention to the proteins involved in oxidative stress and tubular injury.

MATERIAL AND METHODS

Prospective quantitative proteomic comparison of pooled urine from RS (N=30, 24 females, mean age 12.95±4.03

years) versus age- and gender-matched HC (N=30), using mass spectrometry. Proteins of interest were selected using

the following criteria: 1) ≥5 spectral counts; 2) ≥2-fold difference in spectral counts; and 3) ≤0.05 p-value for the

Fisher's Exact Test, and were confirmed by ELISA.

RESULTS

Of the 1813 proteins identified, 230 met the above criteria, with 163 proteins up-regulated in RS group. Function

analysis revealed 23 inflammatory proteins, 8 proteins involved in oxidative stress, and 6 involved in tubular injury

(apolipoprotein A-IV APO A4, liver-type fatty acid binding protein L-FABP, beta 2-microglobulin, retinol-binding protein

4, cystatin C, and lysozyme C) . ELISA analysis revealed significantly increased urinary levels of APO A4 only in

hypercalciuria (N=10) versus controls (median 341.23 ng/mg creatinine vs median 89.62 ng/mg creatinine, p=0.01).

Additionally, hypercalciuric children showed significantly higher urinary levels of L-FABP compared to controls (median

30.64 ng/mg creatinine vs median 5.73 ng/mg creatinine, p=0.05).

CONCLUSIONS

We provide proteomic evidence of oxidative stress, inflammation, and tubular injury in children with renal stones. We

speculate that inflammation and changes in the oxidant-antioxidant balance may cause tubular damage in these

patients. Urinary Apo A4 and L-FABP represent novel biomarkers for tubular injury in children with hypercalciuria and

kidney stones.