ESPN 51th Annual Meeting

ESPN 2018


 
Oxidative Stress in Pediatric Nephrolithiasis: Proteomic Evidence
LARISA KOVACEVIC 1 HONG LU 1 JOSEPH CARUSO 2 YEGAPPAN LAKSHMANAN 1

1- CHILDRENS HOSPITAL OF MICHIGAN
2- INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES, WAYNE STATE UNIVERSITY
 
Introduction:

Experimental and animal studies have shown crystal-induced oxidative stress and tubular injury in kidney cells. However, there is little evidence of oxidative imbalance in pediatric nephrolithiasis. We aimed to investigate whether oxidative stress is present in children with stones (RS) compared to healthy controls (HC) by measuring urinary proteins involved in this process.

Material and methods:

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 liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. 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.

Results:

Of the 1813 proteins identified, 230 met the above criteria, with 163 proteins up-regulated in the RS group and 67 up-regulated in HC. Five proteins involved in oxidative stress were over-represented in stone children. Of those, NADPH-oxidase, a major source of reactive oxygen species, was only found in the RS group, while glutathione S-transferase A2, an important antioxidant enzyme, was more abundant in controls (Table).

Accession Number1

Assigned peptides2 [Patient - Control]

Ratio (Patient/Control)

Fishers Exact Test (p-Value)

BLVRB

5 - 0

Unique

0.0630

CATA

13 - 0

Unique

0.0003

SODC

35 - 13

2.69

0.0034

PERM

95 - 43

2.21

˂ 0.0001

GSTA2

19 - 38

0.59

0.0076

 1 UniProt accession number; 2Represents the spectral count, or total number of MS/MS spectra assigned to each protein; BLVRB-flavin reductase; CATA- catalase, SODC-Cu/Zn superoxide dismutase; PERM- myeloperoxidase, GSTA2- glutathione S-transferase A2

 

Conclusions:

We provide proteomic evidence of oxidative stress in children with renal stones. We speculate that changes in the oxidant-antioxidant balance may cause tubular dysfunction in these patients. Targeting these proteins may have therapeutic benefits.