Gaurav Gupta1, Bassam G Abu Jawdeh, Lorraine C Racusen, Bhavna Bhasin, Lois J Arend, Brandon Trollinger, Edward Kraus, Hamid Rabb, Andrea A Zachary, Robert A Montgomery, Nada Alachkar. 1. 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.
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.
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.
Authors: L Qin; G Li; N Kirkiles-Smith; P Clark; C Fang; Y Wang; Z-X Yu; D Devore; G Tellides; J S Pober; D Jane-Wit Journal: Am J Transplant Date: 2016-06-14 Impact factor: 8.086
Authors: K Iwasaki; H Hamana; H Kishi; T Yamamoto; T Hiramitsu; M Okad; T Tomosugi; A Takeda; S Narumi; Y Watarai; Y Miwa; M Okumura; Y Matsuoka; K Horimi; A Muraguchi; T Kobayash Journal: Clin Exp Immunol Date: 2020-07-18 Impact factor: 4.330
Authors: Farsad Eskandary; Heinz Regele; Lukas Baumann; Gregor Bond; Nicolas Kozakowski; Markus Wahrmann; Luis G Hidalgo; Helmuth Haslacher; Christopher C Kaltenecker; Marie-Bernadette Aretin; Rainer Oberbauer; Martin Posch; Anton Staudenherz; Ammon Handisurya; Jeff Reeve; Philip F Halloran; Georg A Böhmig Journal: J Am Soc Nephrol Date: 2017-12-14 Impact factor: 10.121