Increased incidence of urinary matrix metalloproteinases as predictors of disease in pediatric patients with inflammatory bowel disease

Background: Matrix metalloproteinases (MMPs) are a family of metal-dependent enzymes responsible for the degradation and remodeling of extracellular matrix and basement membrane proteins that occurs during both normal physiologic activity and disease. It has been suggested that MMPs may also play a role in the pathogenesis of inflammatory bowel disease (IBD) by mediating mucosal breakdown in response to an enhanced inflammatory cascade. We previously demonstrated that elevated urinary MMP levels are independent predictors of disease status in cancer patients. Here we demonstrate that elevated urinary MMP levels may be biomarkers of disease activity in patients with IBD. Methods: We analyzed 95 urine samples prospectively collected from 55 children and young adults with known or suspected IBD who presented for evaluation to the Gastrointestinal Procedure Unit at Children's Hospital Boston. Urinary MMPs were analyzed in patients by zymography and compared to 40 age- and sex-matched controls. Results: Urinary MMP levels were significantly elevated (P < 0.0001) in patients with IBD, as well as in each subgroup (Crohn's disease or ulcerative colitis), relative to controls. Multiple logistic regression revealed that urinary MMP-2 and MMP-9 NGAL levels were independent predictors of Crohn's disease and ulcerative colitis (P < 0.0001). Conclusions: These data are the first to demonstrate that urinary MMPs may represent novel noninvasive biomarkers for use in the evaluation of patients with IBD.