Renal allograft pathology in the sensitized patient

Patterns of renal allograft injury associated with alloantibody have been increasingly recognized over the past 2 decades. The use of more sensitive serum testing has brought to light the range of alloantibody-associated changes on biopsy at different time points posttransplant. There is likely to be an increasing number of patients with preformed alloantibody undergoing kidney transplantation, and so alloantibody-associated injury will become more prevalent.

Acute antibody-mediated rejection (AMR) is a major complication in kidney transplant patients with preformed donor-specific antibody (DSA), particularly in the early posttransplant period. Acute AMR is characterized by acute tissue injury and is likely to be antibody mediated and complement mediated. A recent study showed a decreased risk of acute AMR with terminal complement pathway inhibition. Other studies have shown endothelialitis, a vascular lesion traditionally associated with acute cellular rejection, in AMR. Features of chronic AMR are common and include transplant glomerulopathy, peritubular capillary basement membrane multilamination, and accelerated arteriosclerosis. Although previously a diagnosis of humoral rejection usually required complement factor C4d deposition in the graft, we now recognize chronic features because of DSA even in the absence of C4d deposition.

Acute and chronic AMR are major contributors to renal allograft dysfunction and loss. Recognition of tissue injury patterns associated with alloantibody can lead to treatment strategies in patients with DSA and can aid in interpreting biopsies in patients who are receiving new therapies.