Introduction

In the last two decades, existing immunosuppressive agents have significantly improved short-term graft survival in renal transplant recipients. However, this improvement has failed to translate into long-term survival [1].

Apart from death with a functioning transplant, chronic rejection has emerged as a leading cause of renal allograft loss [1]. There is currently no specific therapy for chronic rejection. Identification of treatment strategies that result in enduring benefits in the long term has therefore become essential. Any such study on longterm treatment strategies must evaluate the effect of treatment over several years' post-transplantation and will take between 5 and 10 years to complete. This is hardly feasible and, therefore, it has become important to identify and characterize appropriate near-term surrogate end-points [2]. Such a surrogate end-point should be visible between 1 or 2 years' post-transplantation and should predict graft loss 5–10 years' post-transplantation, even if the function of the graft at the time of measurement is normal.

In this chapter, we will briefly describe some silent features of chronic allograft rejection, particularly in kidney transplants, and propose the use of protocol core needle biopsy as a surrogate end-point in clinical studies.

Clinical manifestations and prevention of chronic rejection

Chronic kidney allograft rejection is both a clinical and a histological diagnosis. Clinically, it manifests as progressive deterioration of renal function in the absence of other causes [3]. However, the natural history of chronic rejection is quite variable in terms of the time of onset and speed of progression [4].