Cleaved Form of Osteopontin in Urine as a Clinical Marker of Lupus Nephritis

PLoS One. 2016 Dec 19;11(12):e0167141. doi: 10.1371/journal.pone.0167141. eCollection 2016.

Abstract

We assessed the utility of two forms of osteopontin (OPN), OPN full and its cleaved form (OPN N-half), in plasma and urine as markers of disease activity in lupus nephritis (LN). Samples were collected from patients with systemic lupus erythematosus (SLE) (LN: N = 29, non-LN: N = 27), IgA nephropathy (IgAN) (N = 14), minimal change nephrotic syndrome (MCNS) (N = 5), diabetic nephropathy (DN) (N = 14) and healthy volunteers (HC) (N = 17). While there was no significant difference in urine OPN full concentration between groups, urine OPN N-half concentration was significantly higher in patients with LN than HC (p < 0.05). Moreover, urine OPN N-half was higher in LN patients with overt proteinuria (urine protein/creatinine ratio: P/C > 0.5) than LN patients with minimal proteinuria (P/C < 0.5, p < 0.0001), and also higher than in DN patients with overt proteinuria (P/C > 0.5, p < 0.01). Urine thrombin activity correlated with urine OPN N-half concentration (p < 0.0001), but not with urine OPN full concentration. These results suggest that urine OPN N-half concentration reflects renal inflammation. Thus, urine OPN N-half may be a novel disease activity marker for LN.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Biomarkers / urine*
  • Diabetic Nephropathies / metabolism
  • Female
  • Glomerulonephritis, IGA / metabolism
  • Humans
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Nephritis / diagnosis*
  • Lupus Nephritis / metabolism
  • Male
  • Middle Aged
  • Nephrosis, Lipoid / metabolism
  • Osteopontin / blood
  • Osteopontin / urine*
  • Peptide Fragments / blood
  • Peptide Fragments / urine*
  • Thrombin / urine
  • Young Adult

Substances

  • Biomarkers
  • Peptide Fragments
  • SPP1 protein, human
  • osteopontin (1-168), human
  • Osteopontin
  • Thrombin

Grants and funding

This work was supported in part by the Special Coordination Funds for Promoting Science and Technology of the Japanese Government and in part by Astellas Pharma Inc. in the Formation of Innovation Center for Fusion of Advanced Technologies Program. Publication of this article was approved by an intellectual property committee composed of representatives from Kyoto University and Astellas Pharma Inc. TO, CS and YH are employees of Astellas Pharma Inc. The funder provided support in the form of salaries for authors (see above), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.