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2016 ; 92
(ä): 100-5
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Renal Tubular Dysfunction in Pediatric Urolithiasis: Proteomic Evidence
#MMPMID26892647
Kovacevic L
; Lu H
; Caruso JA
; Lakshmanan Y
Urology
2016[Jun]; 92
(ä): 100-5
PMID26892647
show ga
OBJECTIVE: To investigate whether inflammation, oxidation, and tubular injury are
present in children with stones (RS) compared with healthy controls (HC) by
measuring urinary proteins involved in these processes. 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) P-value ?.05 for Fisher's exact test. RESULTS: Of the 1813 proteins
identified, 230 met the above criteria, with 163 proteins upregulated in the RS
group and 67 upregulated in HC. Functional analysis revealed 19 inflammatory
proteins, 5 proteins involved in oxidative stress, and 5 involved in tubular
injury. Of those proteins, NADPH-oxidase, a major source of reactive oxygen
species, was only found in the RS group, whereas glutathione S-transferase A2, an
important antioxidant enzyme, was more abundant in controls. ELISA analysis
confirmed statistically significant differences in the urinary excretion of
retinol-binding protein 4, a marker of proximal tubular dysfunction, between
stone patients with hypercalciuria and controls. CONCLUSION: 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. Targeting
these proteins may have therapeutic benefits.