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Comparative Study
. 2016;43(4):293-303.
doi: 10.1159/000445448. Epub 2016 May 3.

Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria

Ellen R Brooks  1 , Bernd Hoppe, Dawn S Milliner, Eduardo Salido, John Rim, Leah M Krevitt, Julie B Olson, Heather E Price, Gulsah Vural, Craig B Langman
Affiliations
Comparative Study

Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria

Ellen R Brooks et al. Am J Nephrol. 2016.

Abstract

Background: Primary hyperoxaluria type 1 (PH1) and idiopathic hypercalciuria (IHC) are stone-forming diseases that may result in the formation of calcium (Ca) oxalate (Ox) stones, nephrocalcinosis, and progressive chronic kidney disease (CKD). Poorer clinical outcome in PH1 is segregated by the highest urine (Ur)-Ox (UrOx), while IHC outcomes are not predictable by UrCa. We hypothesized that differences would be found in selected Ur-protein (PRO) patterns in PH1 and IHC, compared to healthy intra-familial sibling controls (C) of PH1 patients. We also hypothesized that the PRO patterns associated with higher UrOx levels would reflect injury, inflammation, biomineralization, and abnormal tissue repair processes in PH1.

Methods: Twenty four-hour Ur samples were obtained from 3 cohorts: PH1 (n = 47); IHC (n = 35) and C (n = 13) and were analyzed using targeted platform-based multi-analyte profile immunoassays and for UrOx and UrCa by biochemical measurements.

Results: Known stone matrix constituents, osteopontin, calbindin, and vitronectin were lowest in PH1 (C > IHC > PH1; p < 0.05). Ur-interleukin-10; chromogranin A; epidermal growth factor (EGF); insulin-like growth factor-1 (IGF-1), and macrophage inflammatory PRO-1α (MIP-1α) were higher in PH1 > C (p = 0.03 to p < 0.05). Fetuin A; IGF-1, MIP-1α, and vascular cell adhesion molecule-1 were highest in PH1 > IHC (p < 0.001 to p = 0.005).

Conclusion: PH1 Ur-PROs reflected overt inflammation, chemotaxis, oxidative stress, growth factors (including EGF), and pro-angiogenic and calcification regulation/inhibition compared to the C and IHC cohorts. Many of the up- and downregulated PH1-PROs found in this study are also found in CKD, acute kidney injury, stone formers, and/or stone matrices. Further data analyses may provide evidence for PH1 unique PROs or demonstrate a poorer clinical outcome.

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Conflict of interest statement

The authors have no personal or financial conflict of interests regarding any organizations or individuals that could be perceived as influencing this research, its design, implementation, or results published.

Figures

Figure 1
Figure 1. Median IGF-1 in the urine of control, IHC and PH1 cohorts
PH1>Controls; PH1>IHC. Data are log transformed. Abbreviations: IGF-1: Insulin-like growth factor-1; IHC: Idiopathic hypercalciurics; PH1: Primary hyperoxaluria, type 1.
Figure 2
Figure 2. Known stone matrix components are lower in PH1 urine
Data are log transformed and expressed as mean±S.D. Abbreviations: OPN: Osteopontin; IHC: Idiopathic hypercalciurics; PH1: Primary hyperoxaluria, type 1. (a) Osteopontin (Controls>IHC>PH1; *p<0.05) (b) Calbindin (Controls>IHC>PH1; *p<0.05)
See this image and copyright information in PMC

References

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Publication types

Supplementary concepts