Clinical outcomes of plasma exchange in acute and chronic antibody-mediated rejection following kidney transplantation: a prospective observational study
DOI:
https://doi.org/10.18203/2320-6012.ijrms20261857Keywords:
Antibody-mediated rejection, Kidney transplantation, Plasma exchange, Donor-specific antibody, Renal allograft, Graft survivalAbstract
Background: Antibody-mediated rejection (ABMR) remains a major cause of renal allograft dysfunction and graft loss after kidney transplantation. Plasma exchange (PE) is widely used for antibody removal; however, its effectiveness in acute and chronic ABMR remains incompletely defined.
Methods: This prospective observational study was conducted at the Institute of Kidney Diseases and Research Centre–Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, Gujarat, India. The study included 60 kidney transplant recipients with biopsy-proven ABMR treated between September 2017 and November 2019. Patients were classified as acute ABMR (n=30) or chronic ABMR (n=30) according to Banff criteria. All patients received plasma exchange in combination with corticosteroids, intravenous immunoglobulin, and optimization of maintenance immunosuppression. Demographic, clinical, histopathological, immunological, and renal outcomes were assessed at baseline, 6 months, and 5 years.
Result: Baseline demographic and laboratory characteristics were comparable between groups (p>0.05). Acute ABMR demonstrated significant improvement in histological activity scores following treatment, including C4d, glomerulitis, peritubular capillaritis, and vasculitis (p≤0.002), whereas chronic ABMR showed no significant histological improvement (p>0.05). At 6 months, acute ABMR was associated with significantly better renal function, lower proteinuria, and lower donor-specific antibody levels than chronic ABMR (all p<0.001). At 5 years, acute ABMR maintained superior renal outcomes with lower serum creatinine, lower proteinuria, lower persistent donor-specific antibody positivity, and higher estimated glomerular filtration rate (p<0.001). Chronic ABMR was associated with more hospitalizations (p<0.001), infection-related admissions (p=0.004), cardiovascular events (p=0.002), mortality (p=0.044), and graft loss requiring maintenance dialysis (p=0.026).
Conclusion: Plasma exchange is associated with substantial histological and functional recovery in acute ABMR but provides limited benefit in chronic ABMR. Early diagnosis and intervention may improve long-term allograft survival and clinical outcomes.
References
Loupy A, Lefaucheur C. Antibody-mediated rejection of solid-organ allografts. N Engl J Med. 2018;379(12):1150-60.
Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12(2):388-99.
Hart A, Lentine KL, Smith JM, Miller JM, Skeans MA, Prentice M, et al. OPTN/SRTR 2019 Annual Data Report: Kidney. Clin Transplant. 2021;35:e14320.
Vázquez-Toledo MA, Hernández-Fuentes MP, Hidalgo LG, Einecke G, Halloran PF, Sis B, et al. Molecular mechanisms of antibody-mediated rejection in kidney transplantation. Int J Mol Sci. 2025;26:6011.
Naesens M, Roufosse C, Haas M, Loupy A, Mengel M, Colvin RB, et al. The evolution of Banff classification for kidney transplant pathology. Am J Transplant. 2024;24:338-49.
Sapir-Pichhadze R, Wiebe C, Gibson IW, Ho J, Birk PE, Tinckam KJ, et al. Precision medicine in kidney transplantation: role of molecular phenotyping. Clin Transplant. 2025;39:e70167.
Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, et al. The Banff 2017 Kidney Meeting Report: revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 2018;18(2):293-307.
Surdi LM, Pober JS, Colvin RB, Halloran PF, Hidalgo LG, Einecke G, et al. Endothelial cell injury and microvascular inflammation in kidney allografts. Transplantation. 2025;109:258-69.
Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, et al. Recommended treatment for antibody-mediated rejection after kidney transplantation: the 2019 expert consensus from the Transplantation Society Working Group. Transplantation. 2020;104(5):911-22.
Alasfar S, Montgomery RA. Management of antibody-mediated rejection: current status and future directions. Kidney Int Rep. 2023;8(9):1741-55.
Böhmig GA, Naesens M, Viklicky O, Thaunat O, Diebold M, Rostaing L, et al. Antibody-mediated rejection-treatment standard. Nephrol Dial Transplant. 2025;40(8):1615-27.
Palmisano A, Gandolfini I, Gentile M, Benigno GD, Delsante M, D'Angelo M, et al. The Treatment of Acute Antibody-Mediated Rejection: Current State and Future Perspectives. G Ital Nefrol. 2024;41(Suppl 83):2024.
Diebold M, Thaunat O, Böhmig GA, Viklicky O, Rostaing L, Wekerle T, et al. Reversibility of acute antibody-mediated rejection in renal allografts. Transplantation. 2025;109:625-38.
Wellekens K, Naesens M, Loupy A, Haas M, Roufosse C, Mengel M, et al. Chronic antibody-mediated rejection: a paradigm shift in management. Am J Transplant. 2025;25:1123-33.
Elahi T, Hussain N, Kumar D, Sharma A, Gupta R, Patel M, et al. Histological progression and clinical outcomes of chronic active antibody-mediated rejection. World J Transplant. 2026;16:111524.
Montgomery RA, Loupy A, Segev DL. Plasma exchange and intravenous immune globulin for the treatment of antibody-mediated rejection. Am J Transplant. 2016;16(12):3468-78.
Macklin PS, Morris PJ, Knight SR. A systematic review of the use of rituximab for the treatment of antibody-mediated renal transplant rejection. Transplant Rev (Orlando). 2017;31(2):87-95.
Sautenet B, Blancho G, Büchler M, Morelon E, Toupance O, Barrou B, et al. One-year results of the effects of rituximab on acute antibody-mediated rejection in kidney transplantation: RITUX ERAH, a multicenter double-blind randomized placebo-controlled trial. Transplantation. 2016;100(2):391-9.
Orandi BJ, Zachary AA, Dagher NN, Bagnasco SM, Garonzik-Wang JM, Van Arendonk KJ, et al. Presentation and outcomes of antibody-mediated rejection after kidney transplantation. Am J Transplant. 2016;16(1):213-20.
Moreso F, Crespo M, Ruiz JC, Torres A, Gutierrez-Dalmau A, Osuna A, et al. Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: A multicenter, prospective, randomized, double-blind clinical trial. Am J Transplant. 2018;18(4):927-35.
Madill-Thomsen KS, Cristoferi I, Varol H, van Baardwijk M, Rahiem L, Lila KA, et al. Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass. Kidney Int. 2024;105(4):812-23.
Mayrdorfer M, Halloran PF, Budde K, Reeve J, Hidalgo LG, Famulski KS, et al. Interstitial fibrosis and tubular atrophy in chronic antibody-mediated rejection. J Am Soc Nephrol. 2021;32(6):1513-26.
Levine MH, Kick J, Rees MA, Randhawa P, Wiseman AC, Bromberg JS, et al. Reversibility of microvascular inflammation and progression to transplant glomerulopathy. Clin J Am Soc Nephrol. 2011;6:2786-93.
Hart A, Schladt DP, Matas AJ, Itzler R, Israni AK, Kasiske BL. Incidence, risk factors, and long-term outcomes associated with antibody-mediated rejection - The long-term Deterioration of Kidney Allograft Function (DeKAF) prospective cohort study. Clin Transplant.2021;35(7):e14337.
Redfield RR, Ellis TM, Zhong W, Scalea JR, Zens TJ, Mandelbrot DA, et al. Current outcomes of chronic active antibody mediated rejection – A large single-center retrospective review using the updated Banff 2013 criteria. Hum Immunol. 2016;77(4):346-52.
Moss E, Burrell A, Lee J, Reichenbach D, Mitchell S, Yan S, et al. Economic and humanistic burden in kidney transplant rejection: a literature review. Expert Rev Pharmacoecon Outcomes Res. 2024;24(3):343-52.
Loupy A, Hill GS, Jordan SC. The impact of donor-specific anti-HLA antibodies on late kidney allograft failure. N Engl J Med. 2013;369(13):1215-26.
Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG, et al. Antibody-mediated micro-circulation injury is the major cause of late kidney transplant failure. J Am Soc Nephrol. 2009;20(10):2064-74.
Everly MJ, Rebellato LM, Haisch CE, Ozawa M, Parker K, Briley KP, et al. Impact of donor-specific antibodies on long-term renal allograft survival. Am J Transplant. 2009;9:1098-107.
Zarkhin V, Li L, Kambham N, Sigdel T, Salvatierra O, Sarwal MM. A randomized trial of rituximab for acute pediatric renal transplant rejection. Am J Transplant. 2008;8:2607-17.
Jordan SC, Choi J, Kim I, Wu G, Toyoda M, Shin B, et al. Tocilizumab for the treatment of active antibody-mediated rejection in kidney transplant recipients. N Engl J Med. 2017;377:442-53.
Choi J, Aubert O, Vo A, Loupy A, Haas M, Puliyanda D, et al. Long-term outcomes of tocilizumab therapy for chronic antibody-mediated rejection. Am J Transplant. 2017;17:2381-9.
Eskandary F, Regele H, Baumann L, Bond G, Kozakowski N, Wahrmann M, et al. A randomized trial of bortezomib in late antibody-mediated kidney transplant rejection. J Am Soc Nephrol. 2018;29(2):591-605.
Roufosse C, Simmonds N, Clahsen-van Groningen M, Haas M, Henriksen KJ, Horsfield C, et al. A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology. Kidney Int. 2018;93(3):568-79.
Doberer K, Eskandary F, Kozakowski N, Wahrmann M, Bond G, Regele H, et al. CD38 antibody therapy for refractory antibody-mediated kidney transplant rejection. Transplantation. 2021;105(3):e29-e31.
Lefaucheur C, Loupy A, Vernerey D, Duong-Van-Huyen JP, Suberbielle C, Anglicheau D, et al. Antibody-mediated rejection of kidney allografts: population-based study. Lancet. 2013;381(9863):313-9.
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