[Functional loss of the transplanted kidney: immunological and non-immunological factors]

During the past few years, the short-term graft survival after kidney transplantation has improved dramatically, a phenomenon not paralleled by an increase in the long-term graft survival. This is due to the progressive renal injury and dysfunction known as chronic transplant nephropathy or 'chronic rejection', a process that involves both immune and non-immune factors. Immunological factors include T- and B-cell recognition of alloantigens, cytomegalovirus infection, and endothelial cell activation followed by vascular smooth cells proliferation. Among nonimmune mechanisms, proteinuria and hypertension play a relevant role. Moreover, the reduced number of functioning nephrons may trigger an inflammatory process that, eventually, contributes to the loss of the graft. Several studies have documented the efficacy of blocking the renin-angiotensin system (RAS) in reducing proteinuria and preventing renal function deterioration in experimental models of chronic rejection. Early results are promising. However, available clinical trials are rather limited in terms of number of patients enrolled, consequently they cannot be considered definitive. Since several pathogenetic factors are involved in the progression of chronic transplant nephropathy, a multidrug approach with specific immunosuppressants and RAS-blocking drugs has been proposed to control/prevent chronic injury and progressive renal deterioration. Preliminary results in experimental models are promising. Data from prospective clinical trials are, however, mandatory to confirm the efficacy of a polypharmacological strategy in preventing chronic rejection.