Background: Successful reversal of early post-transplant antibody mediated rejection (AMR) is well documented, but data on the results of treatment of late AMR are lacking. We present a single center experience of 13 consecutive patients treated for late AMR.

Methods: All recipients of a primary kidney-only transplant between 2008-2012 at our institution were retrospectively reviewed. Late AMR was defined as rejection > 6 months posttransplant. Diffuse/circumferential C4d positivity and peritubular capillaritis along with presence of de-novo anti-HLA donor-specific antibodies (DSA) were used to diagnose AMR in for-cause biopsies. Median follow up post biopsy was 290 days (63-2048 days).

Results: Out of 517 primary renal transplants done during this period, 13 patients had late AMR occurring 7-24 months post-transplant: 10/13(77%) had mixed AMR and cell-mediated rejection; transplant glomerulopathy and peritubular capillary basement membrane multilayering were seen in 3 patients (23%); 61%(8/13) patients had moderate to severe IF-TA. Proteinuria at biopsy varied between none to 2.8 g/g of creatinine. Noncompliance contributed to rejection in 5/13(38%) patients. Treatment: 6/13(46%) patients received plasmapheresis + intravenous immune globulin (IVIg) + thymoglobulin^R + IV steroids; 5/13 patients received rituximab + the above combination. One patient with pure AMR was treated with plasmapheresis + IVIg alone; 1 patient received only steroids(had severe IFTA). While initial improvement was observed in 9/13(69%) patients, with a decline in SCr from 7.9(+/- 6.2) to 3.1(+/- 1.0) mg/dl and decline in DSA strength, sustained improvement was seen only in 4/13(31%) patients over 250-2048 days. No improvement was seen in patients who presented with a SCr >6.1 mg/dl, except in 1 patient. Overall incidence of graft loss was 46%(6/13) within 8 months of treatment of late AMR; 31%(4/13) of patients had serious infections (blastomycosis, pyelonephritis, cytomegalovirus syndrome and bacteremia) after treatment for AMR and 1 patient (8%) died from severe sepsis.

Conclusions: Our data suggest poor response to therapy in patients treated for AMR >6 months post-transplant, with unacceptably high risk of infectious complications. The risk of therapy of late AMR should be weighed against benefits, especially in patients with advanced renal failure and/or histological findings suggesting chronicity.

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