ESPN 51th Annual Meeting

ESPN 2018


 
Urinary proteomics reveals association between pediatric nephrolithiasis and cardiovascular disease
LARISA KOVACEVIC 1 Hong Lu 1 JOSEPH A CARUSO 2 NATALIJA KOVACEVIC 1 YEGAPPAN LAKSHMANAN 1

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

We aimed to study (1) the differences in the relative abundance of urinary proteins between children with kidney stones (RS) and hypercalciuria, hypocitraturia, normal metabolic work-up, and healthy controls (HC); and (2) the association of these proteins with various diseases.

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, 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, 229 met the above criteria, with 162 proteins up-regulated in the RS group and 67 up-regulated in HC. The largest group of proteins (30 out of 229) was found to be associated with cardiovascular disease (CVD). Of those, 7 were exclusively found in RS group (Table).

Accession Number

Protein

Assigned peptides [Patient - Control]

P-Value

F13B

Coagulation factor XIII

25-0

< 0.0001

FIBG

Fibrinogen gamma

13-0

0.0019

FABP4

Fatty acid binding protein 4

9-0

0.0018

CATA

Catalase

9-0

0.013

KLKB1

Kallikrein 1B

8-0

0.021

GUC2B

Guanylate cyclase activator 2B

7-0

0.0072

FBN2

Fibrillin 2

5-0

0.030

16/30 proteins were involved in coagulation, and adhesion, 10/30 in inflammation, 5/30 in lipid transport and metabolism, and 4/30 in oxidative stress. 28/30 proteins were exclusively found in children with hypercalciuria and hypocitraturia, and were not seen in children with normal metabolic work up.

Conclusions:

Using a proteomic approach, we found a significant association between hypercalciuric and hypocitraturic nephrolithiasis and CVD in children. The shared risk factors among both diseases are endothelial dysfunction and atherosclerosis caused by abnormal coagulation, adhesion, disturbance of lipid transport and metabolism, oxidative stress and inflammation. Further understanding of the pathophysiological link between nephrolithiasis and CVD is necessary for developing new therapeutic targets.