Late kidney dysfunction in a kidney transplant recipient

Abstract

Late kidney transplant dysfunction may be a harbinger of graft failure. For many years, calcineurin inhibitor toxicity was felt to be the main cause for graft dysfunction with fibrosis and transplant loss. Recently this idea has come into question. With the observation that peritubular capillary C4d staining in kidney allografts may indicate antibody-mediated injury in conjunction with biopsy study findings, an appreciation for antibody-mediated rejection as a major cause of late graft dysfunction and loss has emerged. Twenty percent to 30% of patients develop de novo donor-specific antibodies after kidney transplantation. There are no US Food and Drug Administration-approved treatments for antibody-mediated rejection, nor have any randomized controlled trials assessed efficacy. Off-label treatment strategies include some combination of plasma exchange, intravenous immunoglobulin, and rituximab. Other approaches, including splenectomy, bortezomib, and eculizumab, have also been tried.

Figure 1.

Several peritubular capillaries (arrows) contain increased numbers of leukocytes, which is a histologic feature suggestive of antibody-mediated rejection. Stain: periodic acid–Schiff; original magnification, ×200.

Figure 2.

This glomerulus demonstrates focal duplication of the glomerular basement membranes (arrows), a pathologic finding consistent with chronic antibody-mediated rejection. Stain: Jones methenamine silver; original magnification, ×400.

Figure 3.

Strong C4d deposition of the peritubular capillaries is a characteristic feature of antibody-mediated rejection in the allograft kidney. Indirect immunofluorescence microscopy; original magnification, ×200.

Figure 4.

C4d deposition. (A) Schematic depiction. (B) Detection by indirect immunofluorescence.