Chronic rejection and late renal allograft dysfunction.

Renal transplantation is currently standard therapy for end-stage kidney disease for children. Despite the considerable improvement in short-term results, the expected allograft half-life has remained the same. This is due to chronic rejection/late graft dysfunction which has proved resistant to therapeutic attempts. During the last few years the multifactorial pathogenesis of chronic renal allograft rejection has been clarified to some extent. Early injury by immunological and non-immunological mechanisms is followed by vascular remodelling due to repetitive cycles of cytokine release, upregulation of growth factors, and vascular smooth muscle cell proliferation. This leads to typical concentric arteriosclerosis and ischemia. Secondary kidney-specific mechanisms are initiated by the reduction in functioning renal mass and lead to gradual progression of chronic rejection. There is no single optimal therapy. Several attempts to influence the pathophysiological cascade have been promising. Attention should be focused on minimizing early immunological/non-immunological injury in order to attenuate future progression of chronic rejection. A significant prolongation of allograft half-life may be achieved during the next decade with the introduction of new therapeutic agents and comprehensive approach to treatment. This would be especially beneficial for pediatric recipients, reducing the need for retransplantation in adulthood.