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Published on: February 9, 2021
Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with
Larisa Kovacevic1, Hong Lu2, Joseph A Caruso3
1Department of Pediatric Urology, Children's Hospital of Michigan, Detroit, MI, USA. lkovacev@dmc.org.
Insights
Children with kidney stones and hypercalciuria show increased urinary excretion of lipid transport proteins. This suggests a potential role for lipid metabolism abnormalities in kidney stone formation.
Area of Science:
- Biochemistry
- Proteomics
- Pediatric Nephrology
Background:
- Kidney stones in children are often associated with metabolic abnormalities like hypercalciuria.
- The role of lipid metabolism in pediatric kidney stone formation is not well understood.
Purpose of the Study:
- To identify and compare urinary proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria.
- To confirm proteomic findings using ELISA and examine correlations with clinical parameters.
Main Methods:
- Proteomic analysis (liquid chromatography-mass spectrometry) of pooled urine from children with kidney stones (hypercalciuria, hypocitraturia) and controls.
- ELISA confirmation on individual samples.
- Correlation analysis with demographic, dietary, blood, and urinary parameters.
Main Results:
- Five key proteins involved in lipid metabolism and transport (APOA2, APOA4, APOC3, FABPL, FABP4) were identified with significant differences in the hypercalciuria group compared to controls.
- ELISA confirmed elevated urinary excretion of APOC3, APOA4, and FABPL in the hypercalciuria group.
- Urinary calcium excretion significantly correlated with urinary APOC3 and FABPL concentrations.
Conclusions:
- Proteomic analysis reveals increased urinary excretion of lipid metabolism and transport proteins in children with kidney stones and hypercalciuria.
- These findings suggest that dysregulation of lipid metabolism may contribute to the pathogenesis of kidney stones in children.
Background:
Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters.
Methods:
Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples.
Results:
Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r = 0.77, p < 0.001), and FABPL (r = 0.80, p = 0.005).
Conclusions:
We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.
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