Histological markers of chronic allograft nephropathy (CAN) in early protocol biopsies may ultimately result in deterioration of graft function. The aim of our study was to evaluate risk factors of early CAN histology and to determine whether treatment of borderline and subclinical acute rejections (BR/SAR) at 1-month posttransplant, prevents development and/or progression of CAN at 6-month biopsy. Thirty-five paired kidney allograft biopsies at 1 and 6 months after transplantation were blindly reviewed using Banff'97 criteria. The mean CAN score (sum of histological markers for chronicity) increased significantly at 6-month biopsy (1.83 +/- 1.46 vs 4.66 +/- 2.35; p < 0.01). No CAN was present in 27/70 biopsies (38.6%), 71.4% showed progression and 28.6% were with stable CAN at 6-month biopsy. When compared according to the progression, mean histological index (HI) score (sum of acute/chronic changes) in progressed CAN group (pCAN) increased significantly at 6-month biopsy (5.0 +/- 3.0 vs 9.5 +/- 2.8; p < 0.001). At 1-month biopsy, BR/SAR were found in 68% and 70%, in the pCAN and stable (sCAN) groups, respectively. The percentage of treated BR/SAR in sCAN group was significantly higher (57.1 vs 23.5%; p < 0.05), and the score of acute histological lesions lower (1.08 +/- 0.95 vs 0.35 +/- 0.66; p < 0.01) at 6-month biopsy. In conclusion, 1-month protocol biopsy may be valuable to uncover BR/SAR and the presence of early CAN in stable renal allografts. Progression of CAN at 6-month biopsy in our study was found to be associated with a greater number of untreated BR/SAR at 1-month biopsy. This observation may have important implications in the design of clinical trials aimed to prevent the progression of CAN.