Insights into subclinical rejection.

Several groups have performed graft biopsies at set times posttransplant ("protocol biopsies") and found unequivocal histologic criteria for acute rejection in a high proportion of patients with stable graft function. The significance of "subclinical" rejection remains controversial. Our group and others have shown that clinically silent infiltrates have inflammatory and cytotoxic potential. Furthermore, in a randomized trial, we demonstrated that treatment of subclinical rejection results in better graft histology and renal function. Although a decrease in the prevalence of subclinical rejection may reduce the rate of late graft losses, the risks and cost of protocol biopsies require that noninvasive methods for the diagnosis of subclinical rejection be developed.