Renal dysfunction and intragraft pro MMP 9 activity in renal transplant recipients with interstitial fibrosis and tubular atrophy

Summary Chronic renal allograft injury is reflected by interstitial fibrosis and tubular atrophy ( IF / TA ) and by the accumulation of extracellular matrix ( ECM ). Metalloproteinases ( MMP s) are renal physiologic regulators of ECM degradation. Changes in MMP s expression or activity may disturb ECM turnover leading to glomerular scarring and worsening renal function. Our goal was to investigate intragraft MMP 2 and MMP 9 activities and their correlation with renal dysfunction. Plasma MMP 2 and MMP 9 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 MMP 2 and MMP 9 activities were analyzed by zymography. A significant renal dysfunction was observed in IF / TA + patients. Intragraft pro MMP 9 showed a significant higher activity in IF / TA + than in IF / TA − samples and was inversely correlated with the GFR . Intragraft pro MMP 2 activity tended to increase in IF / TA + samples, although no statistic significance was reached. Circulating pro MMP 2 and pro MMP 9 activities did not show significant differences between groups. Our data provide evidence that correlates intragraft pro MMP 9 activity with the fibrotic changes and renal dysfunction observed in IF / TA .