The role of matrixmetalloproteinases (MMPs) in renal interstitial fibrosis

Renal interstitial fibrosis (RIF) is the end result of chronic kidney disease (CKD) and is predictive of long-term renal survival and its inhibition might delay progression towards end-stage renal disease (ESRD). Since type IV collagen-rich extracellular matrix is replaced by type-1 collagen after injury, the hypothesis is being tested that matrix metalloproteinase-2 (MMP-2), a type IV collagenase, may play a causative role in renal fibrosis. Mechanistic studies are underway using an MMP-2 -/- mouse to determine whether MMP-2 promotes renal tubular epithelial-mesenchymal transition (EMT), myofibroblast proliferation and fibrogenesis with and without unilateral ureteral obstruction (UUO), a murine model of RIF.

In addition, the role of MMP-2 in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) is under study comparing MMP-2 and fibrognesis marker gene and protein expression by human ADPKD epithelia versus normal renal tubular cell lines in vitro.

Frequent Hemodialysis Network (FHN): Short Daily Dialysis Study

Previously published data suggests that short daily hemodialysis (2-2.5 hours a day, 6 days a week) may be superior to conventional hemodialysis (3-4 hours a day, 3 days a week) in terms of solute clearance and fluid management. Daily hemodialysis could result in improved dialysis adequacy, improved blood pressure control, decreased cardiac disease (specifically, left ventricular hypertrophy), and decreased mortality. We are working with RRI (Renal Research Institute) as part of a multi-center NIH funded clinical trial studying the potential benefits of short daily hemodialysis versus conventional hemodialysis.

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Bansal MB, Kovalovich K, Gupta R, Li W, Agarwal A, Radbill B, Alvarez CE, Safadi R, Fiel MI, Friedbam SL, Taub RA. Interleukin-6 protects hepatocytes from CCl4-mediated necrosis and apoptosis in mice by reducing MMP-2 expression. J Hepatol 2005 Apr; 42(4): 548-56.