Protocol biopsies in renal transplantation: prognostic value of structural monitoring

Abstract

The natural history of renal allograft damage has been characterized in serial protocol biopsies. The prevalence of subclinical rejection (SCR) is maximal during the first months and it is associated with the progression of interstitial fibrosis/tubular atrophy (IF/TA) and a decreased graft survival. IF/TA rapidly progress during the first months and constitutes an independent predictor of graft survival. IF/TA associated with transplant vasculopathy, SCR, or transplant glomerulopathy implies a poorer prognosis than IF/TA without additional lesions. These observations suggest that protocol biopsies could be considered a surrogate of graft survival. Preliminary data suggest that the predictive value of protocol biopsies is not inferior to acute rejection or renal function. Additionally, protocol biopsies have been employed as a secondary efficacy variable in clinical trials. This strategy has been useful to demonstrate a decrease in the progression of IF/TA in some calcineurin-free regimens. Quantification of renal damage is associated with graft survival suggesting that quantitative parameters might improve the predictive value of protocol biopsies. Validation of protocol biopsies as a surrogate of graft survival is actively pursued, as the utility of classical surrogates of graft outcome such as acute rejection has become less useful because of its decreased prevalence with actual immunosuppression.