Kidney transplantation is a form of renal replacement therapy that gives the greatest benefits for patients with chronic kidney disease (CKD). Transplantation is more effective (medically and economically) than chronic dialysis therapy, with lower mortality rate and twice longer life expectancy, and improved quality of life (1). The clinical goal of transplantation is long-lasting patients’ and grafts’ survival. Despite improvements in immunosuppression and increased knowledge about the processes taking place in the transplanted organ, long-term graft survival is not satisfactory. In some patients after kidney transplantation, within a short time, develop processes of interstitial fibrosis and tubular atrophy (IF/TA), resulting in a chronic allograft injury (CAI) and graft loss in more than 50% of renal transplant recipients (RTR) after several years. In 10 years these patients need dialysis treatment and re-transplantation. Chronic allograft injury (CAI) remains the most important single cause of late graft loss after kidney transplantation (2-4). In two last decades of 20th century graft survival improved significantly and 1-year renal allografts survival rates are over 80% for cadaveric and 90-95% for living related donors (5). Despite reducing the frequency and severity of acute rejection episodes, calcineurin inhibitors (Tac and CsA) have no protective effect on the development of chronic allograft dysfunction (2), with inconsiderable improvement of the half-life of renal allografts, and renal allografts continue to be lost at the rate of 2 to 4% per year due to CAI (6, 7). More than 1 million of renal transplant recipients live over the world. The mechanisms of fibrosis are complex, and may involve excess synthesis of collagen with decreased degradation, in association with interstitial injury and loss of functional tubules and glomeruli. Better understanding of mechanisms of interstitial fibrosis and tubular atrophy (IF/TA), as the morphological surrogate of renal allograft deterioration may improve outcome after renal transplantation (8).

Chronic allograft injury (CAI) is a multifactorial clinical and pathological entity with progressive decline in glomerular filtration rate (GFR) and not fully understood etiology (9). Both immune (antigen dependent) and nonimmune (antigen independent) events may promote graft injury (10). Wide repertoire of factors is involved: chemokines, profibrotic cytokines, growth factors, pro-angiogenic factors and proteolytic enzymes. The whole sequence of events is taken into account, ranging from the excessive accumulation of extracellular matrix (ECM) to reduced degradation of ECM proteins by proteolytic enzymes. One of the possible hypotheses of CAI is irreversible disruption of three-dimensional structure of ECM. Besides ECM expansion also occur significant changes in kidney allografts’ architectonics, with myofibroblasts accumulation and fibrosis induced by epithelial-to-mesenchymal transition, glomerular hypertrophy and sclerosis, as well as tubular atrophy and loss of peritubular capillars. The inflammatory cells (macrophages, various T-cells, dendritic cells, plasma cells and granulocytes) infiltrate is present in acute phase of injury. These findings give the histopathological picture of interstitial fibrosis and tubular atrophy (IF/TA). The term IF/TA is reserved for unclear and unspecific etiology of graft dysfunction. Changes in serum creatinine levels and proteinuria occur late and may not represent the actual state of allograft damage. In protocol biopsies it was shown that structural injury develops early and the presence of IF/TA occurs before functional dysfunction. The presence of IFTA has a predictive impact, independent from other classic factors of graft injury (11). More advanced fibrosis correlate with progressing allograft dysfunction (12).