Submitted on July 9, 2007
Accepted on September 21, 2007
Urinary Matrix Metalloproteinases reflect renal damage in Anti-Neutrophil Cytoplasm Autoantibody-associated vasculitis
Jan-Stephan F. Sanders1*, Minke G. Huitema1, Roeland Hanemaaijer2, Harry van Goor3, Cees G. Kallenberg4, and Coen Albert Stegeman5
1 Internal Medicine, University Medical Center Groningen, Groningen, Netherlands
2 Division of Vascular and Connective Tissue Research, TNO Prevention and Health, Gaubius Laboratory, Leiden, Netherlands
3 Pathology, Univ. Med. Center Groningen, Groningen, Netherlands
4 Internal Medicine, Universitiy Medical Center Groningen, Groningen, Netherlands; Grpningen, Netherlands
5 Internal Medicine, Universitiy Medical Center Groningen, Groningen, Netherlands
* To whom correspondence should be addressed. E-mail: j.sanders{at}int.umcg.nl.
Renal expression of MMP-2, -9, and Tissue Inhibitor of MMP-1 (TIMP-1) correlates with histological disease-activity in 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 ANCA-associated vasculitis.
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 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 tubulo-interstitial damage, and correlate negatively with creatinine clearance at biopsy.
