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Late Antibody-Mediated Rejection in Renal Allografts: Outcome After Conventional and Novel Therapies

Gupta, Gaurav1; Abu Jawdeh, Bassam G.2; Racusen, Lorraine C.3; Bhasin, Bhavna4; Arend, Lois J.3; Trollinger, Brandon5; Kraus, Edward4; Rabb, Hamid4; Zachary, Andrea A.4; Montgomery, Robert A.6; Alachkar, Nada4,7

Transplantation:
doi: 10.1097/01.TP.0000442503.85766.91
Clinical and Translational Research
Abstract

Background: Although several strategies for treating early antibody-mediated rejection (AMR) in kidney transplants have been investigated, evidence on treatment of late AMR manifesting after 6 months is sparse. In this single-center series, we present data on 23 consecutive patients treated for late AMR.

Methods: Late AMR was diagnosed using Banff 2007 criteria along with presence of donor-specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to therapy was assessed by improvement in SCr, histologic improvement, and decline in DSA strength.

Results: Overall, 17% (4/23) had documented nonadherence while 69% (16/23) had physician-recommended reduction in immunosuppression before AMR. Eighteen patients (78%) were treated with plasmapheresis or low-dose IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this improvement was not sustained at most recent follow-up. Eleven (48%) patients had no histologic resolution on follow-up biopsy. Lack of histologic response was associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic vasculopathy (cv≥2) on index biopsy (OR=50; P=0.06).

Conclusions: A major setting in which late AMR occurred in our cohort was reduction or change in immunosuppression. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies. The benefits of therapy need to be counterweighed with potential adverse effects especially in older patients, large antibody loads, and chronic allograft vasculopathy.

Author Information

1 Department of Medicine, Virginia Commonwealth University, Richmond, VA.

2 Department of Medicine, University of Cincinnati, Cincinnati, OH.

3 Department of Pathology, Johns Hopkins University, Baltimore, MD.

4 Department of Medicine, Johns Hopkins University, Baltimore, MD.

5 Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD.

6 Department of Surgery, Johns Hopkins University, Baltimore, MD.

7 Address correspondence to: Nada Alachkar, MD, Johns Hopkins University School of Medicine, 600 Wolfe Street, Brady 502, Baltimore, MD 21287.

E-mail: nalachk1@jhmi.edu

Support was provided by a grant (RC1 DK086731) from the National Institute of Diabetes and Digestive and Kidney Diseases with additional funding from the Charles T. Bauer Foundation (R.A.M.).

The authors declare no conflicts of interest.

G.G. participated in designing and performing the research, writing the article, and analyzing the data. B.G.A. participated in performing the research and collecting clinical data. L.C.R. participated in writing the article. B.B. participated in collecting clinical data. L.J.A. participated in providing the pathology images and writing the article. B.T. participated in collecting the therapeutic data. E.K. participated in writing the article. H.R. participated in writing the article. A.A.Z. participated in reviewing the immunogenetics data. R.A.M. participated in designing the research and writing the article. N.A. participated in designing and performing the research, writing the article, and analyzing the data.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Received 23 July 2013. Revision requested 26 August 2013.

Accepted 19 November 2013.

Accepted February 6, 2014

© 2014 by Lippincott Williams & Wilkins