Assessment of urine proteomics in type 1 primary hyperoxaluria

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

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)293-303
Number of pages11
JournalAmerican journal of nephrology
Volume43
Issue number4
DOIs
StatePublished - Jun 1 2016

Keywords

  • Calcium oxalate crystals
  • Epidermal growth factor
  • Fetuin A
  • Idiopathic hypercalciuria
  • Osteopontin
  • Primary hyperoxaluria type 1
  • Tam Horsfall protein
  • Urine oxalate
  • Urine proteomics

ASJC Scopus subject areas

  • Nephrology

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