Repository hosted by TU Delft Library

Home · Contact · About · Disclaimer ·
 

Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

Publication files not online:

Author: Sanders, J.S.F. · Huitema, M.G. · Hanemaaijer, R. · Goor, H. van · Kallenberg, C.G.M. · Stegeman, C.A.
Type:article
Date:2007
Institution: TNO Kwaliteit van Leven
Source:American Journal of Physiology - Renal Physiology, 6, 293
Identifier: 240326
doi: doi:10.1152/ajprenal.00310.2007
Keywords: Biology · ANCA-associated vasculitis · Crescentic glomerulonephritis · Immunohistochemistry · MMP-2 · MMP-9 · Plasma levels · TIMP-1 · Urinary levels · C reactive protein · Adult · Aged · Aged, 80 and over · Antibodies, Antineutrophil Cytoplasmic · C-Reactive Protein · Creatine · Enzyme-Linked Immunosorbent Assay · Female · Humans · Immunohistochemistry · Kidney Diseases · Kidney Glomerulus · Male · Matrix Metalloproteinases · Middle Aged · Proteinuria · Tissue Inhibitor of Metalloproteinase-1 · Vasculitis

Abstract

Renal expression of MMP-2, -9, and tissue inhibitor of MMP-1 (TIMP-1) correlates with histological disease activity in anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV). We studied whether urinary and plasma levels of MMP-2, -9, and TIMP-1 reflect renal expression of these proteins and renal disease-activity in AAV. Urine and plasma samples of patients with AAV who underwent a renal biopsy were collected (n = 32). Urinary activity of MMP-2 and -9 was measured by activity assays. Urinary and plasma levels of MMP-2, MMP-9, and TIMP-1 proteins were measured by ELISA. Healthy controls provided plasma and urine for comparison (n = 31). In patients, the relationship of urinary and plasma levels with renal expression of MMP-2 and MMP-9 and clinical and histological disease activity was studied. Renal MMP expression was compared between patients and controls (n = 8). Urinary MMP-2 and MMP-9 activity and urinary and plasma TIMP-1 levels were significantly higher in patients than in controls. In glomeruli of patients, both MMP-2 and MMP-9 expression reflected active glomerular inflammation. Urinary activity of MMP-2 and MMP-9 did not correlate with renal MMP expression or plasma levels. Urinary MMP activity correlated negatively with glomerular inflammation, but positively with fibrous crescents. Urinary MMP-2 and TIMP-1 levels showed a positive correlation with tubulointerstitial damage and a negative correlation with creatinine clearance. Urinary MMP-2, MMP-9, and TIMP-1 are elevated in AAV but do not reflect renal MMP expression and glomerular inflammation. However, urinary MMP-2 activity and TIMP-1 levels reflect tubulointerstitial damage and correlate negatively with creatinine clearance at biopsy. Copyright © 2007 the American Physiological Society.