title: Renal dysfunction and intragraft proMMP9 activity in renal transplant recipients with interstitial fibrosis and tubular atrophy.
abstract: Chronic renal allograft injury is reflected by interstitial fibrosis and tubular atrophy (IF/TA) and by the accumulation of extracellular matrix (ECM). Metalloproteinases (MMPs) are renal physiologic regulators of ECM degradation. Changes in MMPs expression or activity may disturb ECM turnover leading to glomerular scarring and worsening renal function. Our goal was to investigate intragraft MMP2 and MMP9 activities and their correlation with renal dysfunction. Plasma MMP2 and MMP9 activities were analyzed as noninvasive markers of renal allograft deterioration. Transplanted patients were biopsied and histopathologically characterized as IF/TA+ or IF/TA-. Renal function was evaluated by serum creatinine, glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease equation and urinary protein/creatinine ratio. Kidney and plasma MMP2 and MMP9 activities were analyzed by zymography. A significant renal dysfunction was observed in IF/TA+ patients. Intragraft proMMP9 showed a significant higher activity in IF/TA+ than in IF/TA- samples and was inversely correlated with the GFR. Intragraft proMMP2 activity tended to increase in IF/TA+ samples, although no statistic significance was reached. Circulating proMMP2 and proMMP9 activities did not show significant differences between groups. Our data provide evidence that correlates intragraft proMMP9 activity with the fibrotic changes and renal dysfunction observed in IF/TA.
authors.affiliation: Servicio de Bioquímica, Hospital Córdoba, Córdoba, Argentina.
authors.forename: María Agustina
authors.initials: MA
authors.lastname: Racca
authors.forename: Pablo Antonio
authors.initials: PA
authors.lastname: Novoa
authors.forename: Iván
authors.initials: I
authors.lastname: Rodríguez
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Della Vedova
authors.forename: Claudia Gabriela
authors.initials: CG
authors.lastname: Pellizas
authors.forename: Marcela
authors.initials: M
authors.lastname: Demarchi
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Donadio
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D001284:Atrophy / Q000601:surgery; D001706:Biopsy; D015331:Cohort Studies; D003928:Diabetic Nephropathies / Q000150:complications / Q000628:therapy; D004032:Diet; D005355:Fibrosis / Q000503:physiopathology / Q000601:surgery; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006085:Graft Survival; D006977:Hypertension, Renal / Q000150:complications / Q000628:therapy; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism; D009393:Nephritis / Q000150:complications / Q000628:therapy
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C522361:MMP2 protein, human; C579270:MMP9 protein, human
keywords: chronic allograft nephropathy; interstitial fibrosis and tubular atrophy; kidney transplantation; metalloproteinases; renal dysfunction