Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplantation. Sep 10, 2018; 8(5): 178-187
Published online Sep 10, 2018. doi: 10.5500/wjt.v8.i5.178
Treatment with plasmapheresis, immunoglobulins and rituximab for chronic-active antibody-mediated rejection in kidney transplantation: Clinical, immunological and pathological results
Alberto Mella, Ester Gallo, Maria Messina, Cristiana Caorsi, Antonio Amoroso, Paolo Gontero, Aldo Verri, Francesca Maletta, Antonella Barreca, Fabrizio Fop, Luigi Biancone
Alberto Mella, Ester Gallo, Maria Messina, Fabrizio Fop, Luigi Biancone, Renal Transplantation Center “A. Vercellone”, Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, Città della Salute e della Scienza Hospital and University of Turin, Turin 10126, Italy
Cristiana Caorsi, Antonio Amoroso, Immunogenetics and Transplant Biology Service, AOU Città della Salute e della Scienza di Torino and Department of Medical Sciences, University of Turin, Turin 10126, Italy
Paolo Gontero, Division of Urology, Department of Surgical Sciences, Città della Salute e della Scienza Hospital and University of Turin, Turin 10126, Italy
Aldo Verri, Division of Vascular Surgery, Department of Thoracic-Vascular Surgery, Città della Salute e della Scienza Hospital, Turin 10126, Italy
Francesca Maletta, Antonella Barreca, Division of Pathology Transplantation, Department of Medical Sciences, University of Turin, Turin 10126, Italy
Author contributions: Mella A, Gallo E, Messina M and Biancone L wrote the main manuscript text; Caorsi C and Amoroso A performed donor specific antibodies and C1q tests; Maletta F and Barreca A revised histological data; Fop F performed statistical analysis; Mella A, Gallo E, Messina M, Caorsi C, Amoroso A, Gontero P, Verri A, Maletta F, Barreca A, Fop F and Biancone L contributed to the conception, design and analysis of the data; Mella A, Gallo E, Messina M, Caorsi C, Amoroso A, Gontero P, Verri A, Maletta F, Barreca A, Fop F and Biancone L contributed to the revision and approval of the final manuscript.
Institutional review board statement: This retrospective analysis doesn’t required an evaluation by our Institutional review board; Authors expressed their adherence to the Declaration of Istanbul
Informed consent statement: We obtained in all treated patients an informed consent about potential complications and adverse events.
Conflict-of-interest statement: On behalf of all authors, the corresponding author states that there is no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Luigi Biancone, MD, PhD, Professor, Renal Transplantation Center “A. Vercellone”, Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, Città della Salute e della Scienza Hospital and University of Turin, Corso Bramante 88, Turin 10126, Italy. luigi.biancone@unito.it
Telephone: +39-11-6336797 Fax: +39-11-6334990
Received: May 2, 2018
Peer-review started: May 3, 2018
First decision: May 22, 2018
Revised: June 14, 2018
Accepted: June 28, 2018
Article in press: June 28, 2018
Published online: September 10, 2018
Abstract
AIM

To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection (cAMR) settings.

METHODS

We compared 21 kidney transplant recipients (KTRs) with a diagnosis of cAMR in a retrospective case-control analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab (PE-IVIG-RTX group) vs 12 patients (control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody (DSA) characteristics (MFI and C1q-fixing ability) were also investigated.

RESULTS

No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group (33.3%) and 4/12 in the control group (33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo (min 12-max 18) and 15 mo (min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cAMR diagnosis were also similar in both groups. Only microvascular inflammation (glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients (87.5%) in the PE-IVIG-RTX group (median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome.

CONCLUSION

Our data showed no difference in the two year post-treatment outcome of kidney grafts treated with PE-IVIG-RTX for cAMR diagnosis, however there were notable improvements in microvascular inflammation in post-therapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.

Keywords: Chronic-active antibody-mediated rejection, Kidney transplantation, Donor-specific antibody, Rituximab

Core tip: Chronic-active antibody-mediated rejection (cAMR) is one of the major causes of poor long-term outcome in kidney transplantation, with no effective treatments currently available. We retrospectively compared 21 kidney transplant recipients with a diagnosis of cAMR, nine treated with plasmapheresis, intravenous immunoglobulins and rituximab vs 12 patients not treated with antibody-targeted therapies. Our data showed improvement in microvascular inflammation in post-therapy protocol biopsies without differences in functional outcomes at 24 mo, suggesting the lack of a prompt and marked effect of this therapeutic protocol. Further studies are required to improve the management and long-term results of this severe condition.