Protocol biopsy: what is the rationale and what is the evidence?

The incidence of acute rejection (and the proportion of grafts lost during the first year after renal transplantation) have markedly decreased after the introduction of cyclosporin A. The reduction of the rate of graft loss after the first year, however, has been much less impressive. Chronic transplant nephropathy has become the most common cause of late graft failure [1]. Chronic allograft nephropathy is strongly correlated with the number of acute rejection episodes during the first year after renal transplantation [2,3]. In the past, the possibility of graft failure was suspected only when a sustained and irreversible decline of renal function was evident, usually in the context of proteinuria and hypertension. Unfortunately, by the time the clinical diagnosis was confirmed by histology renal scarring was usually too advanced to make delayed treatment a promising proposition. Traditionally, renal allograft biopsies were performed mainly in the setting of acute graft dysfunction. Recently, there has been a change of paradigms. Several reports suggested that acute rejection episodes and chronic allograft nephropathy are often subclinical without causing a measurable decrease in renal function. This raises the issue of biopsies of stable allografts (protocol biopsies) and the clinically useful information they provide.