The macrophage infiltration index and matrix metalloproteinase-II expression as a predictor of chronic allograft rejection

The presence of macrophages on renal biopsy specimens is considered an important cofactor in the development of chronic allograft nephropathy (CAN). Macrophages can activate the expression of matrix metalloproteinases (MMP), which induce glomerulosclerosis, arteriosclerosis, and interstitial fibrosis. The aim of our study was to demonstrate if they were related to the development of CAN. We analyzed matrix metalloproteinase (MMP) expression with specific monoclonal antibodies on 53 kidney biopsies performed due to the suspicion of a first acute rejection (AR) episode: 24 of the grafts have been lost due to CAN and the rest are still functioning. The group with CAN showed worse graft function and greater proteinuria from the beginning. The macrophage infiltration index (MI) expression was significantly higher in that group also (18.8 ± 12 vs 12.5 ± 9.15; P < .05), with a more important presence of macrophages in the interstitium and tubules. We observed a positive correlation between MI and tubular infiltration (r2 = 0.52; P < .001) and between MMP-II and MI in the interstitium (r2 = 0.3; P < .05) and with the global MI (r2 = 0.3; P < 0.05). The last correlation was more powerful in the group with CAN (r2 = 0.4; P < .05). According to our experience, global MI and tubular infiltration during an AR episode are good markers of long-term graft survival. The correlation between MI and MMP-II supports the role of macrophages in the development of CAN, although further studies are needed to clarify the nature of this relationship.