Protocol Biopsies: Utility and Limitations

As both T cell and antibody–mediated rejection can have a subclinical phase, protocol biopsies provide an early opportunity to intervene before the onset of clinical allograft dysfunction. Protocol biopsies are usually done after reperfusion to establish baseline, between 3 and 6 months to identify subclinical rejection, and at 6-12 months to assess chronicity and persistent inflammation that have prognostic implication. Treatment of both subclinical T cell and antibody–mediated rejection prevents progression of rejection and development of interstitial fibrosis/tubular atrophy or transplant glomerulopathy. Although subclinical rejection has become less frequent in low-risk patients on triple immunosuppression containing tacrolimus, protocol biopsies may still be useful in selected population. Protocol biopsies are more likely to benefit patients at higher risk for rejection, including those who are highly sensitized, transplanted across donor-specific antibody barriers, or on calcineurin inhibitor/corticosteroids sparing regimens. Interstitial fibrosis on protocol biopsies, especially in conjunction with persistent inflammation, predicts lower allograft survival.