Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis.
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.
Sanders
Jan-Stephan F
JS
Univ. Medical Center Groningen, Dept. of Clinical Immunology, Hanzeplein 1, 9700 GZ Groningen, The Netherlands. j.sanders@int.umcg.nl
Huitema
Minke G
MG
Hanemaaijer
Roeland
R
van Goor
Harry
H
Kallenberg
Cees G M
CG
Stegeman
Coen A
CA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000633:toxicity*; D002097:C-Reactive Protein / Q000378:metabolism; D003401:Creatine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology* / Q000652:urine; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000652:urine; D019278:Matrix Metalloproteinase 3 / Q000652:urine; D020780:Matrix Metalloproteinase 9 / Q000652:urine; D020782:Matrix Metalloproteinases / Q000652:urine*; D008875:Middle Aged; D011507:Proteinuria / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000652:urine; D014657:Vasculitis / Q000139:chemically induced / Q000473:pathology* / Q000652:urine
D019268:Antibodies, Antineutrophil Cytoplasmic; D019715:Tissue Inhibitor of Metalloproteinase-1; D002097:C-Reactive Protein; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D003401:Creatine