Circulating levels of matrix metalloproteinases MMP3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy

Background. Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death wit h functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an imp ortant role. This turnover is regulated by several systems of connective ti ssue proteases, the matrix metalloproteinases family being one of them. Eve ry metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such a s rheumatoid arthritis and glomerulonephritis. The role of metalloproteinas es in the pathogenesis of chronic transplant nephropathy and in kidney tran splantation has not yet been addressed. Methods. We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute re jection, 30 with stable graft function for a time equivalent to chronic tra nsplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors. Results. Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and prote inuria. Serum concentration of proMMP-1 was increased in patients with acut e rejection compared with those with stable graft function and healthy dono rs. Conclusions. Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, su ggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which cou ld be a reflection of the stimulation induced by a number of inflammatory c ytokines produced in such a process.