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

Koji Kitagori,Chiyomi Sasaki,Motoko Yanagita,Yoshitaka Hirayama,Ran Nakashima,Naoichiro Yukawa,Koichiro Ohmura,Takashi Usui,Kosaku Murakami,Tsuneyo Mimori,Kaoru Sakai,Toshiki Nakajima,Hajime Yoshifuji,Daisuke Kawabata,Yoshitaka Imura,Hirofumi Miyata ,Keita Mori ,Tomoyuki Fujii ,Teruo Oku

doi:10.1371/journal.pone.0167141

Koji Kitagori, Chiyomi Sasaki + Show 17 more

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https://doi.org/10.1371/journal.pone.0167141

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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.

Highlights

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive B and T cells and autoantibodies, including anti-nuclear and anti-DNA antibodies
The patients with SLE showed a variety of disease activity indices (SLEDAI), histopathological classes of International Society of Nephrology/Renal Pathology Society (ISN/RPS) and histopathological activity/chronicity indices of National Institutes of Health (NIH)
To assess whether OPN N-half can be used as a marker to identify the site of damage to the nephron, we examined the correlation of urine OPN N-half with markers of proximal tubule damage (ALB, B2M, cystatin C, kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL)), distal tubule damage, and general inflammation (IL-18 and monocyte chemoattractant protein 1 (MCP-1)) in the SLE patients

Summary

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive B and T cells and autoantibodies, including anti-nuclear and anti-DNA antibodies. Lupus nephritis (LN) is one of multiple organ manifestations of SLE, and is an important prognostic factor [1]; new, improved therapeutic approaches and biomarkers are needed. Urine protein and serum creatinine (Cre) are traditionally used as markers of LN. As SLE patients may have several complicating nephropathies in the long course of treatment, including LN, drug-induced nephropathy, and diabetic nephropathy, new markers that can discriminate between these complicated renal lesions are needed. Osteopontin (OPN) is a secretory glycoprotein, whose molecular mass ranges from 44–66 kDa due to variation in glycosylation [2]. OPN is expressed by osteoblasts, macrophages, PLOS ONE | DOI:10.1371/journal.pone.0167141. OPN is expressed by osteoblasts, macrophages, PLOS ONE | DOI:10.1371/journal.pone.0167141 December 19, 2016

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