The significance of subclinical rejection and the value of protocol biopsies.

Subclinical rejection (SCR) is diagnosed by protocol histology with a maximal prevalence occurring early after transplantation, falling to low levels by 1 year. Needle-core biopsy is safe, and the histology obtained fairly reflects subclinical immune activity. Several studies have consistently shown that SCR is associated with chronic tubulointerstitial damage, subsequent renal dysfunction and reduced graft survival. SCR is effectively treated by pulse corticosteroid therapy, although increased baseline immunosuppression may be necessary. A single randomized clinical trial of biopsy and corticosteroid therapy demonstrated significantly improved early structural and functional outcomes, and a (nonsignificant) 17% risk reduction in 4-year graft survival. Three possible approaches include: no protocol biopsies (usually accompanied by powerful immunosuppression); biopsies only in high-risk recipients (who may be difficult to reliably predict) or universal screening protocol biopsy (comprehensive but limited by cost and resource utilization). The appropriate screening methodology for a transplant unit is both a clinical and an economic decision; influenced by the SCR prevalence and potential gains of treatment, against costs and resource utilization. Further trials to quantify the cost-benefit balance in a typical, heterogeneous recipient population using modern immunosuppression are required.