Tubular kidney injury molecule-1 (KIM-1) in human renal disease

被引:452
作者
van Timmeren, M. M.
van den Heuvel, M. C.
Bailly, V.
Bakker, S. J. L.
van Goor, H.
Stegeman, C. A.
机构
[1] Univ Groningen, Med Ctr, Dept Pathol & Lab Med, Sector F, NL-9700 AD Groningen, Netherlands
[2] Univ Groningen, NL-9700 AB Groningen, Netherlands
[3] BIOGEN IDEN Inc, Cambridge, MA USA
[4] Univ Groningen, Med Ctr, Dept Internal Med, NL-9700 AD Groningen, Netherlands
关键词
kidney injury molecule-1; pathophysiology of renal disease and progression; renal biopsy; renal tubular epithelial cells; renal fibrosis; urinary biomarker;
D O I
10.1002/path.2175
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
KIM-1, a transmembrane tubular protein with unknown function, is undetectable in normal kidneys, but is markedly induced in experimental renal injury. The KIM-1 ectodomain is cleaved, detectable in urine, and reflects renal damage. KIM-1 expression in human renal biopsies and its correlation with urinary KIM-1 (uKIM-1) is unknown. In biopsies from various renal diseases (n = 102) and controls (n = 7), the fraction of KIM-1 positive tubules and different renal damage parameters were scored. Double labelling was performed for KIM-1 with macrophages (MO), a-smooth muscle actin (alpha-SMA), proximal (aquaporin-1) and distal (E-cadherin) tubular markers and a dedifferentiation marker (vimentin). uKIM-1 at the time of biopsy (n = 53) was measured by ELISA. Renal KIM-1 was significantly increased in all diseases versus controls (p < 0.05), except minimal change. KIM-I was primarily expressed at the luminal side of dedifferentiated proximal tubules, in areas with fibrosis (a-SMA) and inflammation (NIO). Independent of the disease, renal KIM-1 correlated positively with renal damage, negatively with renal function, but not with proteinuria. uKIM-1 was increased in renal patients versus controls (P < 0.001), including minimal change, and correlated positively with tissue KIM-1 and MO, negatively with renal function, but not with proteinuria. In conclusion, KIM-1 is upregulated in renal disease and is associated with renal fibrosis and inflammation. uKIM-1 is also associated with inflammation and renal function, and reflects tissue KIM-1, indicating that it can be used as a non-invasive biomarker in renal disease. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:209 / 217
页数:9
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