Late acute kidney transplant rejection: clinicopathological correlates and response to corticosteroid therapy

Acute rejection is a major cause of kidney allograft dysfunction. It is important to distinguish between cellular and antibody-mediated rejection to guide the treatment strategy. The management of acute antibody-mediated rejection includes aggressive therapy with plasmapheresis and intravenous immunoglobulin. C4d staining of peritubular capillaries has emerged as a valuable tool in identifying antibody-mediated rejection. Late acute rejection has a worse prognosis than early acute rejection. The clinical and pathological features of late acute kidney allograft rejection are not fully understood. We studied the clinicopathological correlates of late acute rejection in our patient population. During an 8-year period, all patients who had late acute rejection (6 months posttransplant) were identified. Patients with severe chronic changes and transplant glomerulopathy were excluded. Patients were divided into C4d+ and C4d- groups [corrected]. Histopathological features and treatment response were evaluated. Nine patients met inclusion criteria (4 C4d+, 5 C4d-). Maintenance therapy consisted of mycophenolate mofetil, calcineurin inhibitors, and low-dose prednisone. All patients received intravenous methlyprednisolone or high-dose oral prednisone as antirejection therapy. Seventy-five percent of patients in the C4d+ group and 80% of patients in the C4d- group had a clinical response to antirejection therapy. The majority of C4d+ patients with late acute rejection who were treated with corticosteroids alone responded to treatment. The study raises the possibility that a subset of C4d+ patients with acute rejection who do not have severe chronic changes might respond to corticosteroid therapy alone.