Investigation of the clinical significance of a new inflammatory molecule LRG in lupus nephritis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09916
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kochi University (2017-2018); National Institutes of Biomedical Innovation, Health and Nutrition (2016)
• Principal Investigator: FUJIMOTO MINORU 高知大学, 教育研究部医療学系臨床医学部門, 准教授 (00379190)
• Research Collaborator: Lee Hyun
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 膠原病学 / バイオマーカー / 尿検査 / 尿蛋白 / ループス腎炎 / 尿細管障害

Outline of Final Research Achievements

In this study, we showed that LRG is secreted in urine of patients with lupus nephritis. By analyzing lupus model mice, we revealed that LRG in urine is derived from renal tubular epithelial cells. Further analysis on a mouse model of albumin-overloaded renal tubular injury revealed that renal tubular epithelial cells injured due to excessive albumin absorption secret IL-1β, which stimulates tubular epithelial cells themselves to produce LRG. LRG secretion in urine was also observed in patients with contrast-induced acute kidney injury. Our findings collectively indicate that LRG secretion in urine is associated with the progression of renal tubular injury. Given that renal tubular injury is the common pathway to end-stage renal failure, urine LRG can be a biomarker of various kidney diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒト腎疾患で尿中にLRGが分泌されること、尿中のLRGは傷害された腎尿細管上皮に由来し、尿細管障害の進行を反映することを示した。尿細管障害は、急性腎障害もしくは慢性腎臓病から腎不全に至る過程において、ほぼすべての腎疾患で共通にみられる病態である。しかし、糸球体障害を反映するマーカーに比して尿細管障害を検出するマーカーは少ない。尿LRGは、ループス腎炎の評価のみならず、より多くの腎疾患において、尿細管障害マーカーとして臨床的に有用であることが示唆された。