CHRONIC, progressive, and irreversible loss of a transplanted kidney function, previously named CHRONIC ALLOGRAFT nephropathy, is the leading cause of CHRONIC ALLOGRAFT failure among kidney transplant recipients. CHRONIC ALLOGRAFT DYSFUNCTION (CAD) is a multifactorial process associated with progressive interstitial fibrosis and tubular atrophy. Current Data confirms that an additive series of time-dependent immunological factors such as acute and CHRONIC antibody- and/or cell-mediated rejection and nonimmunological factors are involved in development of interstitial fibrosis and tubular atrophy as the fundamental parts of CAD. The use of calcineurin inhibitors has produced a major impact on achieving successful organ transplantation, however, although this assumption has been doubted recently, calcineurin inhibitors are deemed to be associated with nephrotoxicity and subsequent interstitial fibrosis, tubular atrophy, and kidney DYSFUNCTION. The early fibrotic changes are due to implantation stress, T-cell–mediated rejection, and infection, however, usually they do not lead to progressive fibrosis and ALLOGRAFT DYSFUNCTION per se. In the setting of CAD, many factors occurring lately after 1 year, such as CHRONIC antibodymediated rejection, recurrent or de novo glomerulonephritis, and nonadherent adequately address the existence of ongoing injuries and progression to fibrosis. Identification of patients who are at risk, close clinical monitoring, and optimization and individualization of their maintenance immunosuppressive regimen are among the means that could help us to improve the long-term outcome of kidney transplantation.

Background: Granzyme-B is a serine proteinase expressed and released mainly by the cytotoxic T and NK cell. Granules intact Granzyme-B is directly delivered into the target cell, while extracellular Granzyme-B, released in serum leads to nonspecific cleavages of extracellular matrix molecules like vitronectin, collagen, TGF-β, , IL-1 and invites systemic inflammation, tissue remodeling and fibrosis leading to the development of CHRONIC renal ALLOGRAFT DYSFUNCTION. Objective: We aimed to immunophenotype the Granzyme-B positive T-lymphocyte subset and GranzymeB role in the development of CHRONIC renal ALLOGRAFT DYSFUNCTION. Methods: We have analyzed the Granzyme-B + CD8 + T/CD8 neg and Granzyme-B + CD3 + /CD3 neg cell subset by the flowcytometry and serum Granzyme-B level by the enzyme-linked immunosorbent assay. Results: We have found that the frequency of Granzyme-B + CD8 neg CD3 + T cell, Granzyme-B + CD8 low CD3 + T cell and Granzyme-B + CD8 high CD3 + T cell subset was significantly lower and serum Granzyme-B level was significantly higher in CAD group. The frequency of CD3 + T, CD3 neg lymphocyte, CD8 neg CD3 + T, CD8 low CD3 + T, CD8 high CD3 + T, Granzyme-B + CD3 neg CD8 neg lymphocyte was similar between the group. The frequency of CD3 + CD8 neg Gzm-B + cell was negatively correlated with serum creatinine and CD3 + CD8 high Gzm-B + cell was negatively correlated with serum Granzyme-B level. Similarly, Serum Granzyme-B level was positively correlated with serum creatinine, urine proteinuria and negatively with eGFR. Conclusion: The circulating frequency of Granzyme-B + CD8 neg CD3 + T cell, Granzyme-B + CD8 low CD3 + T cell and Granzyme-B + CD8 high CD3 + T cell subsets were significantly lower and serum Granzyme-B level was significantly higher in renal ALLOGRAFT recipients with CAD.

CHRONIC ALLOGRAFT DYSFUNCTION is the most common cause of ALLOGRAFT lost. CHRONIC ALLOGRAFT DYSFUNCTION happens as a result of complex interactions at the molecular and cellular levels. Genetic and environmental factors both influence the evolution and progression of the CHRONIC ALLOGRAFT DYSFUNCTION. Epigenetic modification could be considered as a therapeutically modifiable element to pause the fibrosis process through novel strategies. In this review, the PubMed database was searched for English-language articles on these new areas.

Background: Although the short-term results of kidney transplantation have improved greatly during the past decades, the long-term results have not improved according. Graft loss due to CHRONIC ALLOGRAFT DYSFUNCTION (CAD) is a major concern in renal transplant recipients (RTRs). There is little data about disease progression in this patient population. In this paper, we investigated history of kidney function as the pattern, waiting time and rate of pass from intermediate stages in RTR with CAD.Methods: In a single-center retrospective study, 214 RTRs with CAD investigated at the Urmia University Hospital urmia, Iran from 1997 to 2005.Kidney function at each visit assessed with GFR. We apply NKF and K/DOQI classification of CHRONIC kidney disease (CKD) staging system to determine pattern of disease progression per stage in this group of patients.Results: The pure death-censored graft loss was 26% with mean waiting time 81.7 months.100% of RTRs passed from stage I to II in mean waiting time 26.3 months. The probability of prognostic factors transition from stage II to III was 88.9% with mean waiting time 25.5 months, transition from III to IV was 55.7% with mean waiting time of 24.9 months and transition for stage 4 to IV was 53.5% with mean waiting time of 18.2 months. In overall rate of transition from stage i to j in patients with stage III at the beginning of the study (time of start CAD's process) was faster than others.Conclusions: This study revealed, that kidney function in first years after transplantation is one of the most important II to III of survival probability per stage and death-censored graft loss. Therefore care of RTRs in first year could potentially increase long-term kidney survival.

Introduction. There is little data about the pattern of disease progression in kidney transplant recipients with CHRONIC ALLOGRAFT DYSFUNCTION (CAD). Extrapolating the current classification of CHRONIC kidney disease for CAD, we studied the pattern of progression of CAD in 5 stages among our kidney transplant recipients.Materials and Methods. We performed a retrospective cohort study on 214 kidney transplant recipients with CAD. The selection criteria were a functioning kidney ALLOGRAFT for at least 1 year after transplantation and a progressive decline in ALLOGRAFT function. An event history analysis in survival data was carried out based on the stages of CAD at baseline and the end of the study. Results. At the beginning of the study, 54.7% of the patients had CAD stage 1; 37.9%, stage 2, and 7.5%, stage 3. At the end of study, 10.3% were in stage 2; 39.7%, stage 3; 23.4%, stage 4; and 26.6%, stage 5. Patients with CAD stage 5 were 17.1% of those in stage 1, 32.1% of those in stage 2, and 67.7% of those in stage 3 at baseline. There was a significant correlation between stage of CAD at the beginning of the study and the stage of CAD at the end (r = 0.465, P < .001).Conclusions. Because the decline in kidney ALLOGRAFT function was relatively faster in advanced stages of CAD, strategies to increase ALLOGRAFT survival by improving the baseline level of ALLOGRAFT function can be more effective than strategies to slow down progression of advanced stages of CAD.

Background & Aims: CHRONIC ALLOGRAFT DYSFUNCTION is a major concern for graft loss in Renal Transplant Recipients. This paper investigated the waiting time and death-censored graft survival in renal transplant recipients with CHRONIC ALLOGRAFT DYSFUNCTION. The association between short-term and long-term kidney function in this patients were studied.Materials & Methods: In a single-center retrospective study, 214 renal transplant recipients with CHRONIC ALLOGRAFT DYSFUNCTION were investigated at Urmia University Hospitals from 1997 to 2005. Kidney function at each visit was assessed with GFR. We applied NKF and K/DOQI classification of CHRONIC kidney disease staging system to determine stage of kidney disease in this group of patients. Kaplan-meiers survival analysis and log-rank test were used for data analysis.Results: The pure death-censored graft loss was 26.6% with the mean waiting time of 81.7 months. In overall, death-censored graft loss in Pts with stage 3 at the beginning of the study (start of CHRONIC ALLOGRAFT DYSFUNCTION’s process) is faster than other Pts.Conclusion: The findings show that kidney function in the first year after transplantation is one of the main prognoses on death-censored graft loss. Therefore, care of renal transplant recipients in the first year increases long-term kidney survival.