title: Urinary cystatin C as a renal biomarker and its immunohistochemical localization in anti-GBM glomerulonephritis rats.
abstract: The usefulness of urinary cystatin C for the early detection of renal damage in anti-glomerular basement membrane (GBM) glomerulonephritis rats was investigated and compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF)). Urinary levels of cystatin C increased in anti-GBM glomerulonephritis rats, whereas the conventional markers, plasma creatinine and UN did not, demonstrating its usefulness for the early detection of renal damage associated with anti-GBM glomerulonephritis. As well as cystatin C, urinary β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL also had the potential to detect renal damage associated with anti-GBM glomerulonephritis. Furthermore, the immunohistochemical localization of cystatin C in the kidney was examined. Cystatin C expression was mainly observed in the proximal renal tubules in anti-GBM glomerulonephritis rats, and its expression barely changed with the progression of glomerulonephritis. Cystatin C expression was also observed in the tubular lumen of the cortex and medulla when glomerulonephritis was marked, which was considered to be characteristic of renal damage. In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL could be useful biomarkers of renal damage in anti-GBM glomerulonephritis rats. Immunohistochemical cystatin C expression in the proximal renal tubules was barely changed by the progression of glomerulonephritis, but it was newly observed in the tubular lumen when renal damage was apparent.
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1, Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Togashi
authors.forename: Naoko
authors.initials: N
authors.lastname: Imura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000009:adverse effects / Q000276:immunology; D015415:Biomarkers / Q000652:urine*; D055316:Cystatin C / Q000652:urine*; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology / Q000652:urine*; D007118:Immunoassay; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D055316:Cystatin C; C051951:antiglomerular basement membrane antibody
keywords: Anti-glomerular basement membrane (GBM) glomerulonephritis rats; Cystatin C; Immunohistochemistry; Renal biomarker