Top

Published in:

01-04-2015 | Review Article

Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

Authors: Yolanda W. Ng, Manpreet Singh, Minnie M. Sarwal

Published in: Drugs | Issue 5/2015

Abstract

Kidney transplant is the preferred treatment of pediatric end-stage renal disease. One of the most challenging aspects of pediatric kidney transplant is the prevention and treatment of antibody-mediated rejection (ABMR), which is one of the main causes of graft dysfunction and early graft loss. Most challenges are similar to those faced in adult kidney transplants; however, factors unique to the pediatric realm include naivety of the immune system and the small number of studies and randomized controlled trials available when considering pharmacological treatment options. Here, we present a case of ABMR in a pediatric patient and a review of the pathophysiology, diagnosis, and management of ABMR. ABMR in pediatric kidney transplant continues to be a frustrating condition to treat because (1) there still remain many unidentified potential antigens leading to ABMR, (2) children and adults are at different stages of their immune system development, and, thus, (3) the full pathophysiology of alloimmunity is still not completely understood, and (4) the efficacy and safety of treatment in adults may not be directly translated to children. As we continue to gain a better understanding towards the precise alloimmune mechanism that drives a particular ABMR, we can also improve pharmacotherapeutic choices. With continued research, they will become more precise in treating a particular mechanism versus using a broad scope of immunosuppression such as steroids. However, there is much more to be uncovered, such as identifying more non-human leukocyte antigens and their role in alloimmunity, determining the exact mechanism of adults achieving complete operational tolerance, and understanding the difference between pediatric and adult transplant recipients. Making strides towards a better understanding of these mechanisms will lead to continued efficacy and safety in treatment of pediatric ABMR.

Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG, et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2009;9(11):2520–31. doi:10.1111/j.1600-6143.2009.02799.x.CrossRef

Lee PC, Zhu L, Terasaki PI, Everly MJ. HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss. Transplantation. 2009;88(4):568–74. doi:10.1097/TP.0b013e3181b11b72.PubMedCrossRef

Chaudhuri A, Ozawa M, Everly MJ, Ettenger R, Dharnidharka V, Benfield M, et al. The clinical impact of humoral immunity in pediatric renal transplantation. J Am Soc Nephrol JASN. 2013;24(4):655–64. doi:10.1681/ASN.2012070663.CrossRef

Naesens M, Khatri P, Li L, Sigdel TK, Vitalone MJ, Chen R, et al. Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes. Kidney Int. 2011;80(12):1364–76. doi:10.1038/ki.2011.245.PubMedCrossRef

Kurt-Jones EA, Belko J, Yu C, Newburger PE, Wang J, Chan M, et al. The role of toll-like receptors in herpes simplex infection in neonates. J Infect Dis. 2005;191(5):746–8. doi:10.1086/427339.PubMedCrossRef

Shey MS, Nemes E, Whatney W, de Kock M, Africa H, Barnard C, et al. Maturation of innate responses to mycobacteria over the first nine months of life. J Immunol. 2014;192(10):4833–43. doi:10.4049/jimmunol.1400062.PubMedCentralPubMedCrossRef

Adkins B. T-cell function in newborn mice and humans. Immunol Today. 1999;20(7):330–5.PubMedCrossRef

Salio M, Dulphy N, Renneson J, Herbert M, McMichael A, Marchant A, et al. Efficient priming of antigen-specific cytotoxic T lymphocytes by human cord blood dendritic cells. Int Immunol. 2003;15(10):1265–73.PubMedCrossRef

Kutlu NO, Akinci A, Sonmezgoz E, Temel I, Evliyaoglu E. The effects of androstenediol and dehydroepiandrosterone on the immune response to BCG at puberty. J Trop Pediatr. 2003;49(3):181–5.PubMedCrossRef

10.

Kissick HT, Sanda MG, Dunn LK, Pellegrini KL, On ST, Noel JK, et al. Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc Natl Acad Sci USA. 2014;111(27):9887–92. doi:10.1073/pnas.1402468111.PubMedCentralPubMedCrossRef

11.

Maret A, Coudert JD, Garidou L, Foucras G, Gourdy P, Krust A, et al. Estradiol enhances primary antigen-specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor alpha expression in hematopoietic cells. Eur J Immunol. 2003;33(2):512–21. doi:10.1002/immu.200310027.PubMedCrossRef

12.

Straub RH, Schuld A, Mullington J, Haack M, Scholmerich J, Pollmacher T. The endotoxin-induced increase of cytokines is followed by an increase of cortisol relative to dehydroepiandrosterone (DHEA) in healthy male subjects. J Endocrinol. 2002;175(2):467–74.PubMedCrossRef

13.

Splawski JB, Lipsky PE. Cytokine regulation of immunoglobulin secretion by neonatal lymphocytes. J Clin Investig. 1991;88(3):967–77. doi:10.1172/JCI115400.PubMedCentralPubMedCrossRef

14.

Siegrist CA. Neonatal and early life vaccinology. Vaccine. 2001;19(25–26):3331–46.PubMedCrossRef

15.

Upham JW, Lee PT, Holt BJ, Heaton T, Prescott SL, Sharp MJ, et al. Development of interleukin-12-producing capacity throughout childhood. Infect Immun. 2002;70(12):6583–8.PubMedCentralPubMedCrossRef

16.

Li L, Chaudhuri A, Weintraub LA, Hsieh F, Shah S, Alexander S, et al. Subclinical cytomegalovirus and Epstein–Barr virus viremia are associated with adverse outcomes in pediatric renal transplantation. Pediatr Transplant. 2007;11(2):187–95. doi:10.1111/j.1399-3046.2006.00641.x.PubMedCrossRef

17.

Nalesnik MA. Clinicopathologic characteristics of post-transplant lymphoproliferative disorders. Recent Results Cancer Res Fortschritte der Krebsforschung Progres dans les recherches sur le Cancer. 2002;159:9–18.

18.

Sarwal MM, Ettenger RB, Dharnidharka V, Benfield M, Mathias R, Portale A, et al. Complete steroid avoidance is effective and safe in children with renal transplants: a multicenter randomized trial with three-year follow-up. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2012;12(10):2719–29. doi:10.1111/j.1600-6143.2012.04145.x.CrossRef

19.

Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969;280(14):735–9. doi:10.1056/NEJM196904032801401.PubMedCrossRef

20.

Chemouny JM, Suberbielle C, Rabant M, Zuber J, Alyanakian MA, Lebreton X, et al. De novo donor-specific human leukocyte antigen antibodies in nonsensitized kidney transplant recipients after t cell-mediated rejection. Transplantation. 2014;. doi:10.1097/TP.0000000000000448.PubMed

21.

Sarwal M, Chua M-S, Kambham N, Hsieh S-C, Satterwhite T, Masek M, et al. Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N Engl J Med. 2003;349(2):125–38.PubMedCrossRef

22.

Loupy A, Lefaucheur C, Vernerey D, Prugger C, Duong van Huyen JP, Mooney N, et al. Complement-binding anti-HLA antibodies and kidney-allograft survival. N Engl J Med. 2013;369(13):1215–26. doi:10.1056/NEJMoa1302506.PubMedCrossRef

23.

Cerilli J, Brasile L, Galouzis T, Lempert N, Clarke J. The vascular endothelial cell antigen system. Transplantation. 1985;39(3):286–9.PubMedCrossRef

24.

Paul LC, Baldwin WM 3rd, van Es LA. Vascular endothelial alloantigens in renal transplantation. Transplantation. 1985;40(2):117–23.PubMedCrossRef

25.

Jordan SC, Yap HK, Sakai RS, Alfonso P, Fitchman M. Hyperacute allograft rejection mediated by anti-vascular endothelial cell antibodies with a negative monocyte crossmatch. Transplantation. 1988;46(4):585–7.PubMedCrossRef

26.

Opelz G, Collaborative Transplant S. Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet. 2005;365(9470):1570–6. doi:10.1016/S0140-6736(05)66458-6.PubMedCrossRef

27.

Sumitran-Karuppan S, Tyden G, Reinholt F, Berg U, Moller E. Hyperacute rejections of two consecutive renal allografts and early loss of the third transplant caused by non-HLA antibodies specific for endothelial cells. Transplant Immunol. 1997;5(4):321–7.CrossRef

28.

Zafar MN, Terasaki PI, Naqvi SA, Rizvi SA. Non-HLA antibodies after rejection of HLA identical kidney transplants. Clin Transpl. 2006;421–6.

29.

Sumitran-Holgersson S. Relevance of MICA and other non-HLA antibodies in clinical transplantation. Curr Opin Immunol. 2008;20(5):607–13. doi:10.1016/j.coi.2008.07.005.PubMedCrossRef

30.

Banasik M, Boratynska M, Koscielska-Kasprzak K, Krajewska M, Mazanowska O, Kaminska D, et al. The impact of non-HLA antibodies directed against endothelin-1 type A receptors (ETAR) on early renal transplant outcomes. Transpl Immunol. 2014;30(1):24–9. doi:10.1016/j.trim.2013.10.007.PubMedCrossRef

31.

Sun Q, Liu Z, Chen J, Chen H, Wen J, Cheng D, et al. Circulating anti-endothelial cell antibodies are associated with poor outcome in renal allograft recipients with acute rejection. Clin J Am Soc Ephrol CJASN. 2008;3(5):1479–86. doi:10.2215/CJN.04451007.CrossRef

32.

Butte AJ, Sigdel TK, Wadia PP, Miklos DB, Sarwal MM. Protein microarrays discover angiotensinogen and PRKRIP1 as novel targets for autoantibodies in chronic renal disease. Mol Cell Proteomics MCP. 2011;10(3):M110.000497. doi:10.1074/mcp.M110.000497.

33.

Sis B, Halloran PF. Endothelial transcripts uncover a previously unknown phenotype: C4d-negative antibody-mediated rejection. Curr Opin Organ Transplant. 2010;15(1):42–8. doi:10.1097/MOT.0b013e3283352a50.PubMedCrossRef

34.

Panigrahi A, Gupta N, Siddiqui JA, Margoob A, Bhowmik D, Guleria S, et al. Post transplant development of MICA and anti-HLA antibodies is associated with acute rejection episodes and renal allograft loss. Hum Immunol. 2007;68(5):362–7. doi:10.1016/j.humimm.2007.01.006.PubMedCrossRef

35.

Zou Y, Stastny P, Susal C, Dohler B, Opelz G. Antibodies against MICA antigens and kidney-transplant rejection. N Engl J Med. 2007;357(13):1293–300. doi:10.1056/NEJMoa067160.PubMedCrossRef

36.

Sutherland SM, Li L, Sigdel TK, Wadia PP, Miklos DB, Butte AJ, et al. Protein microarrays identify antibodies to protein kinase Czeta that are associated with a greater risk of allograft loss in pediatric renal transplant recipients. Kidney Int. 2009;76(12):1277–83. doi:10.1038/ki.2009.384.PubMedCrossRef

37.

Jackson AM, Sigdel TK, Delville M, Hsieh SC, Dai H, Bagnasco S, et al. Endothelial cell antibodies associated with novel targets and increased rejection. J Am Soc Nephrol JASN. 2014;. doi:10.1681/ASN.2013121277.

38.

Sigdel TK, Salomonis N, Nicora CD, Ryu S, He J, Dinh V, et al. The identification of novel potential injury mechanisms and candidate biomarkers in renal allograft rejection by quantitative proteomics. Mol Cell Proteomics MCP. 2014;13(2):621–31. doi:10.1074/mcp.M113.030577.CrossRef

39.

van Twillert I, van Gaans-van den Brink JA, Poelen MC, Helm K, Kuipers B, Schipper M, et al. Age related differences in dynamics of specific memory B cell populations after clinical pertussis infection. PloS One. 2014;9(1):e85227. doi:10.1371/journal.pone.0085227.

40.

Comans-Bitter WM, de Groot R, van den Beemd R, Neijens HJ, Hop WC, Groeneveld K, et al. Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations. J Pediatr. 1997;130(3):388–93.PubMedCrossRef

41.

van Gent R, van Tilburg CM, Nibbelke EE, Otto SA, Gaiser JF, Janssens-Korpela PL, et al. Refined characterization and reference values of the pediatric T- and B-cell compartments. Clin Immunol. 2009;133(1):95–107. doi:10.1016/j.clim.2009.05.020.PubMedCrossRef

42.

Morbach H, Eichhorn EM, Liese JG, Girschick HJ. Reference values for B cell subpopulations from infancy to adulthood. Clin Exp Immunol. 2010;162(2):271–9. doi:10.1111/j.1365-2249.2010.04206.x.PubMedCentralPubMedCrossRef

43.

Everly MJ, Everly JJ, Arend LJ, Brailey P, Susskind B, Govil A, et al. Reducing de novo donor-specific antibody levels during acute rejection diminishes renal allograft loss. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2009;9(5):1063–71. doi:10.1111/j.1600-6143.2009.02577.x.CrossRef

44.

Haas M. An updated Banff schema for diagnosis of antibody-mediated rejection in renal allografts. Curr Opin Organ Transplant. 2014;19(3):315–22. doi:10.1097/MOT.0000000000000072.PubMedCrossRef

45.

Racusen LC, Colvin RB, Solez K, Mihatsch MJ, Halloran PF, Campbell PM, et al. Antibody-mediated rejection criteria - an addition to the Banff 97 classification of renal allograft rejection. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2003;3(6):708–14.CrossRef

46.

Vo AA, Choi J, Cisneros K, Reinsmoen N, Haas M, Ge S, et al. Benefits of rituximab combined with intravenous immunoglobulin for desensitization in kidney transplant recipients. Transplantation. 2014;98(3):312–9. doi:10.1097/TP.0000000000000064.PubMedCrossRef

47.

Crespo M, Torio A, Mas V, Redondo D, Perez-Saez MJ, Mir M, et al. Clinical relevance of pretransplant anti-HLA donor-specific antibodies: does C1q-fixation matter? Transpl Immunol. 2013;29(1–4):28–33. doi:10.1016/j.trim.2013.07.002.PubMedCrossRef

48.

Thammanichanond D, Mongkolsuk T, Rattanasiri S, Kantachuvesiri S, Worawichawong S, Jirasiritham S, et al. Significance of C1q-fixing donor-specific antibodies after kidney transplantation. Transplant Proc. 2014;46(2):368–71. doi:10.1016/j.transproceed.2013.11.011.PubMedCrossRef

49.

Sicard A, Ducreux S, Rabeyrin M, Couzi L, McGregor B, Badet L, et al. Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of humoral rejection predicts renal graft loss. J Am Soc Nephrol JASN. 2014;. doi:10.1681/ASN.2013101144.

50.

Gulleroglu K, Baskin E, Bayrakci US, Turan M, Ozdemir BH, Moray G, et al. Antibody-mediated rejection and treatment in pediatric patients: one center’s experience. Exp Clin Transplant Off J Middle East Soc Organ Transplant. 2013;11(5):404–7.

51.

Loupy A, Suberbielle-Boissel C, Hill GS, Lefaucheur C, Anglicheau D, Zuber J, et al. Outcome of subclinical antibody-mediated rejection in kidney transplant recipients with preformed donor-specific antibodies. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2009;9(11):2561–70. doi:10.1111/j.1600-6143.2009.02813.x.CrossRef

52.

Naesens M, Salvatierra O, Benfield M, Ettenger RB, Dharnidharka V, Harmon W, et al. Subclinical inflammation and chronic renal allograft injury in a randomized trial on steroid avoidance in pediatric kidney transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2012;12(10):2730–43. doi:10.1111/j.1600-6143.2012.04144.x.CrossRef

53.

Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010;362(20):1890–900. doi:10.1056/NEJMoa0912965.PubMedCrossRef

54.

Sarwal M, Sigdel T. A common blood gene assay predates clinical and histological rejection in kidney and heart allografts. Clin Transpl. 2013;241–7.

55.

Chen R, Sigdel TK, Li L, Kambham N, Dudley JT, Hsieh SC, et al. Differentially expressed RNA from public microarray data identifies serum protein biomarkers for cross-organ transplant rejection and other conditions. PLoS Comput Biol. 2010;6(9). doi:10.1371/journal.pcbi.1000940.

56.

Khatri P, Roedder S, Kimura N, De Vusser K, Morgan AA, Gong Y, et al. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation. J Exp Med. 2013;210(11):2205–21. doi:10.1084/jem.20122709.PubMedCentralPubMedCrossRef

57.

Halloran PF, Pereira AB, Chang J, Matas A, Picton M, De Freitas D, et al. Microarray diagnosis of antibody-mediated rejection in kidney transplant biopsies: an international prospective study (INTERCOM). Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2013;13(11):2865–74. doi:10.1111/ajt.12465.CrossRef

58.

Loupy A, Lefaucheur C, Vernerey D, Chang J, Hidalgo LG, Beuscart T, et al. Molecular microscope strategy to improve risk stratification in early antibody-mediated kidney allograft rejection. J Am Soc Nephrol JASN. 2014;25(10):2267–77. doi:10.1681/ASN.2013111149.CrossRef

59.

Li L, Khatri P, Sigdel TK, Tran T, Ying L, Vitalone MJ, et al. A peripheral blood diagnostic test for acute rejection in renal transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2012;12(10):2710–8. doi:10.1111/j.1600-6143.2012.04253.x.CrossRef

60.

Roedder S, Sigdel T, Salomonis N, Hsieh S, Dai H, Bestard O, et al. The kSORT assay to detect renal transplant patients at high risk for acute rejection: results of the multicenter AART study. PLoS Med. 2014;11(11):e1001759. doi:10.1371/journal.pmed.1001759.PubMedCentralPubMedCrossRef

61.

Hayde N, Broin PO, Bao Y, de Boccardo G, Lubetzky M, Ajaimy M, et al. Increased intragraft rejection-associated gene transcripts in patients with donor-specific antibodies and normal biopsies. Kidney Int. 2014;86(3):600–9. doi:10.1038/ki.2014.75.PubMedCrossRef

62.

Jackups R Jr, Canter C, Sweet SC, Mohanakumar T, Morris GP. Measurement of donor-specific HLA antibodies following plasma exchange therapy predicts clinical outcome in pediatric heart and lung transplant recipients with antibody-mediated rejection. J Clin Apher. 2013;28(4):301–8. doi:10.1002/jca.21270.PubMedCrossRef

63.

Okafor C, Ward DM, Mokrzycki MH, Weinstein R, Clark P, Balogun RA. Introduction and overview of therapeutic apheresis. J Clin Apher. 2010;25(5):240–9.PubMedCrossRef

64.

Montgomery RA, Zachary AA, Racusen LC, Leffell MS, King KE, Burdick J, et al. Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients. Transplantation. 2000;70(6):887–95.PubMedCrossRef

65.

Rocha PN, Butterly DW, Greenberg A, Reddan DN, Tuttle-Newhall J, Collins BH, et al. Beneficial effect of plasmapheresis and intravenous immunoglobulin on renal allograft survival of patients with acute humoral rejection. Transplantation. 2003;75(9):1490–5. doi:10.1097/01.TP.0000060252.57111.AC.PubMedCrossRef

66.

Ruangkanchanasetr P, Satirapoj B, Termmathurapoj S, Namkhanisorn K, Suaywan K, Nimkietkajorn V, et al. Intensive plasmapheresis and intravenous immunoglobulin for treatment of antibody-mediated rejection after kidney transplant. Exp Clin Transplant Off J Middle East Soc Organ Transplant. 2014;12(4):328–33.

67.

Nguyen S, Gallay B, Butani L. Efficacy of bortezomib for reducing donor-specific antibodies in children and adolescents on a steroid minimization regimen. Pediatr Transplant. 2014;18(5):463–8. doi:10.1111/petr.12274.PubMedCrossRef

68.

Zarkhin V, Lovelace PA, Li L, Hsieh SC, Sarwal MM. Phenotypic evaluation of B-cell subsets after rituximab for treatment of acute renal allograft rejection in pediatric recipients. Transplantation. 2011;91(9):1010–8. doi:10.1097/TP.0b013e318213df29.PubMedCrossRef

69.

Becker YT, Becker BN, Pirsch JD, Sollinger HW. Rituximab as treatment for refractory kidney transplant rejection. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2004;4(6):996–1001. doi:10.1111/j.1600-6143.2004.00454.x.CrossRef

70.

Faguer S, Kamar N, Guilbeaud-Frugier C, Fort M, Modesto A, Mari A, et al. Rituximab therapy for acute humoral rejection after kidney transplantation. Transplantation. 2007;83(9):1277–80. doi:10.1097/01.tp.0000261113.30757.d1.PubMedCrossRef

71.

Kaposztas Z, Podder H, Mauiyyedi S, Illoh O, Kerman R, Reyes M, et al. Impact of rituximab therapy for treatment of acute humoral rejection. Clin Transplant. 2009;23(1):63–73. doi:10.1111/j.1399-0012.2008.00902.x.PubMedCrossRef

72.

Hychko G, Mirhosseini A, Parhizgar A, Ghahramani N. A Systematic Review and Meta-Analysis of Rituximab in Antibody-mediated Renal Allograft Rejection. Int J Organ Transplant Med. 2011;2(2):51–6.PubMedCentralPubMed

73.

Kahwaji J, Najjar R, Kancherla D, Villicana R, Peng A, Jordan S, et al. Histopathologic features of transplant glomerulopathy associated with response to therapy with intravenous immune globulin and rituximab. Clin Transplant. 2014;28(5):546–53. doi:10.1111/ctr.12345.PubMedCrossRef

74.

Delbue S, Ferraresso M, Elia F, Belingheri M, Carloni C, Signorini L, et al. Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab. J Med Virol. 2012;84(9):1464–70. doi:10.1002/jmv.23339.PubMedCrossRef

75.

Kahwaji J, Sinha A, Toyoda M, Ge S, Reinsmoen N, Cao K, et al. Infectious complications in kidney-transplant recipients desensitized with rituximab and intravenous immunoglobulin. Clin J Am Soc Nephrol CJASN. 2011;6(12):2894–900. doi:10.2215/CJN.03710411.CrossRef

76.

Salmasi G, Li M, Sivabalasundaram V, Panzarella T, Tsang R, Kukreti V, et al. Incidence of pneumonitis in patients with non-Hodgkin lymphoma receiving chemoimmunotherapy with Rituximab. Leuk Lymphoma. 2014;1–19. doi:10.3109/10428194.2014.963075.

77.

Perry DK, Burns JM, Pollinger HS, Amiot BP, Gloor JM, Gores GJ, et al. Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2009;9(1):201–9. doi:10.1111/j.1600-6143.2008.02461.x.CrossRef

78.

Patel J, Everly M, Chang D, Kittleson M, Reed E, Kobashigawa J. Reduction of alloantibodies via proteasome inhibition in cardiac transplantation. J Heart Lung Transplant Off Publ Int Soc Heart Transplant. 2011;30(12):1320–6. doi:10.1016/j.healun.2011.08.009.CrossRef

79.

Paterno F, Shiller M, Tillery G, O’Leary JG, Susskind B, Trotter J, et al. Bortezomib for acute antibody-mediated rejection in liver transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2012;12(9):2526–31. doi:10.1111/j.1600-6143.2012.04126.x.CrossRef

80.

Tzvetanov I, Spaggiari M, Joseph J, Jeon H, Thielke J, Oberholzer J, et al. The use of bortezomib as a rescue treatment for acute antibody-mediated rejection: report of three cases and review of literature. Transplant Proc. 2012;44(10):2971–5. doi:10.1016/j.transproceed.2012.02.037.PubMedCrossRef

81.

Hardinger KL, Murillo D. The influence of bortezomib on donor specific antibody reduction in patients with antibody mediated rejection. Clin Transpl. 2011;401–8.

82.

Sureshkumar KK, Hussain SM, Marcus RJ, Ko TY, Khan AS, Tom K, et al. Proteasome inhibition with bortezomib: an effective therapy for severe antibody mediated rejection after renal transplantation. Clin Nephrol. 2012;77(3):246–53.PubMedCrossRef

83.

Yang KS, Jeon H, Park Y, Jo IH, Kim JI, Moon IS, et al. Use of bortezomib as anti-humoral therapy in kidney transplantation. J Korean Med Sci. 2014;29(5):648–51. doi:10.3346/jkms.2014.29.5.648.PubMedCentralPubMedCrossRef

84.

Gupta G, Abu Jawdeh BG, Racusen LC, Bhasin B, Arend LJ, Trollinger B, et al. Late antibody-mediated rejection in renal allografts: outcome after conventional and novel therapies. Transplantation. 2014;97(12):1240–6. doi:10.1097/01.TP.0000442503.85766.91.PubMedCrossRef

85.

Sberro-Soussan R, Zuber J, Suberbielle-Boissel C, Legendre C. Bortezomib alone fails to decrease donor specific anti-HLA antibodies: 4 case reports. Clin Transpl. 2009;433–8.

86.

Kranz B, Kelsch R, Kuwertz-Broking E, Brocker V, Wolters HH, Konrad M. Acute antibody-mediated rejection in paediatric renal transplant recipients. Pediatr Nephrol. 2011;26(7):1149–56. doi:10.1007/s00467-011-1864-3.PubMedCrossRef

87.

Morrow WR, Frazier EA, Mahle WT, Harville TO, Pye SE, Knecht KR, et al. Rapid reduction in donor-specific anti-human leukocyte antigen antibodies and reversal of antibody-mediated rejection with bortezomib in pediatric heart transplant patients. Transplantation. 2012;93(3):319–24. doi:10.1097/TP.0b013e31823f7eea.PubMedCentralPubMedCrossRef

88.

Claes DJ, Yin H, Goebel J. Protective immunity and use of bortezomib for antibody-mediated rejection in a pediatric kidney transplant recipient. Pediatr Transplant. 2014;18(4):E100–5. doi:10.1111/petr.12256.PubMedCrossRef

89.

De Serres SA, Mfarrej BG, Magee CN, Benitez F, Ashoor I, Sayegh MH, et al. Immune profile of pediatric renal transplant recipients following alemtuzumab induction. J Am Soc Nephrol JASN. 2012;23(1):174–82. doi:10.1681/ASN.2011040360.CrossRef

90.

Kirk AD, Hale DA, Mannon RB, Kleiner DE, Hoffmann SC, Kampen RL, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation. 2003;76(1):120–9. doi:10.1097/01.TP.0000071362.99021.D9.PubMedCrossRef

91.

Bartosh SM, Knechtle SJ, Sollinger HW. Campath-1H use in pediatric renal transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2005;5(6):1569–73. doi:10.1111/j.1600-6143.2005.00879.x.CrossRef

92.

Csapo Z, Benavides-Viveros C, Podder H, Pollard V, Kahan B. Campath-1H as rescue therapy for the treatment of acute rejection in kidney transplant patients. Transplant Proc. 2005;37(5):2032–6.PubMedCrossRef

93.

Jirasiritham S, Khunprakant R, Techawathanawanna N, Jirasiritham S, Mavichak V. Treatment of simultaneous acute antibody-mediated rejection and acute cellular rejection with alemtuzumab in kidney transplantation: a case report. Transplant Proc. 2010;42(3):987–9. doi:10.1016/j.transproceed.2010.03.018.PubMedCrossRef

94.

Thomas PG, Ishihara K, Vaidya S, Gugliuzza KK. Campath and renal transplant rejection. Clin Transplant. 2004;18(6):759–61. doi:10.1111/j.1399-0012.2004.00288.x.PubMedCrossRef

95.

Locke J, Zachary A, Haas M, Melancon J, Warren D, Simpkins C, et al. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant. 2007;7(4):842–6.PubMedCrossRef

96.

Vincenti F, Larsen CP, Alberu J, Bresnahan B, Garcia VD, Kothari J, et al. Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2012;12(1):210–7. doi:10.1111/j.1600-6143.2011.03785.x.CrossRef

97.

Rahimzadeh N, Otukesh H, Hoseini R, Riahifard A. Pretransplant Epstein–Barr virus serostatus and incidence of posttransplant lymphoproliferative disorder in pediatric renal transplants. Exp Clin Transplant Off J Middle East Soc Organ Transplant. 2013;11(4):299–302.

98.

Ellis D, Jaffe R, Green M, Janosky JJ, Lombardozzi-Lane S, Shapiro R, et al. Epstein–Barr virus-related disorders in children undergoing renal transplantation with tacrolimus-based immunosuppression. Transplantation. 1999;68(7):997–1003.PubMedCrossRef

99.

Wistinghausen B, Gross TG, Bollard C. Post-transplant lymphoproliferative disease in pediatric solid organ transplant recipients. Pediatr Hematol Oncol. 2013;30(6):520–31. doi:10.3109/08880018.2013.798844.PubMedCrossRef

100.

Jordan SC, Vo AA, Toyoda M, Tyan D, Nast CC. Post-transplant therapy with high-dose intravenous gammaglobulin: applications to treatment of antibody-mediated rejection. Pediatr Transplant. 2005;9(2):155–61. doi:10.1111/j.1399-3046.2005.00256.x.PubMedCrossRef

101.

Tyan DB, Li VA, Czer L, Trento A, Jordan SC. Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation. 1994;57(4):553–62.PubMedCrossRef

102.

Stegall MD, Diwan T, Raghavaiah S, Cornell LD, Burns J, Dean PG, et al. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2011;11(11):2405–13. doi:10.1111/j.1600-6143.2011.03757.x.CrossRef

103.

Locke JE, Magro CM, Singer AL, Segev DL, Haas M, Hillel AT, et al. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2009;9(1):231–5. doi:10.1111/j.1600-6143.2008.02451.x.CrossRef

104.

Orandi BJ, Zachary AA, Dagher NN, Bagnasco SM, Garonzik-Wang JM, Van Arendonk KJ, et al. Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation. Transplantation. 2014;98(8):857–63. doi:10.1097/TP.0000000000000298.PubMedCrossRef

105.

Ghirardo G, Benetti E, Poli F, Vidal E, Della Vella M, Cozzi E, et al. Plasmapheresis-resistant acute humoral rejection successfully treated with anti-C5 antibody. Pediatr Transplant. 2014;18(1):E1–5. doi:10.1111/petr.12187.PubMedCrossRef

106.

Burbach M, Suberbielle C, Brocheriou I, Ridel C, Mesnard L, Dahan K, et al. Report of the inefficacy of eculizumab in two cases of severe antibody-mediated rejection of renal grafts. Transplantation. 2014;98(10):1056–9. doi:10.1097/TP.0000000000000184.PubMedCrossRef

107.

Billing H, Rieger S, Ovens J, Süsal C, Melk A, Waldherr R, et al. Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients. Transplantation. 2008;86(9):1214–21.PubMedCrossRef

108.

Twombley K, Thach L, Ribeiro A, Joseph C, Seikaly M. Acute antibody-mediated rejection in pediatric kidney transplants: a single center experience. Pediatr Transplant. 2013;17(7):E149–55. doi:10.1111/petr.12129.PubMed

109.

Comoli P, Quartuccio G, Cioni M, Parodi A, Nocera A, Basso S, et al. Posttransplant soluble B-cell activating factor kinetics in pediatric recipients of first kidney allograft. Transplantation. 2015;99(1):243–9. doi:10.1097/TP.0000000000000276.PubMedCrossRef

110.

Gokmen R, Hernandez-Fuentes MP. Biomarkers of tolerance. Curr Opin Organ Transplant. 2013;18(4):416–20. doi:10.1097/MOT.0b013e3283636fd5.PubMed

111.

Soulillou JP, Giral M, Brouard S. Operational tolerance in kidney transplantation-improved terminology may enable more precise investigation. Transplantation. 2013;96(5):e36–8. doi:10.1097/TP.0b013e31829f75c1.PubMedCrossRef

112.

Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2008;8(4):753–60. doi:10.1111/j.1600-6143.2008.02159.x.CrossRef

113.

Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999;55(2):713–23. doi:10.1046/j.1523-1755.1999.00299.x.PubMedCrossRef

114.

Solez K, Benediktsson H, Cavallo T, Croker B, Demetris AJ, Drachenberg C, et al. Report of the third Banff conference on allograft pathology (July 20–24, 1995) on classification and lesion scoring in renal allograft pathology. Transplant Proc. 1996;28(1):441–4.

115.

Solez K, Axelsen RA, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int. 1993;44(2):411–22.PubMedCrossRef

116.

Steinmetz OM, Lange-Husken F, Turner JE, Vernauer A, Helmchen U, Stahl RA, et al. Rituximab removes intrarenal B cell clusters in patients with renal vascular allograft rejection. Transplantation. 2007;84(7):842–50. doi:10.1097/01.tp.0000282786.58754.2b.PubMedCrossRef

117.

Mulley WR, Hudson FJ, Tait BD, Skene AM, Dowling JP, Kerr PG, et al. A single low-fixed dose of rituximab to salvage renal transplants from refractory antibody-mediated rejection. Transplantation. 2009;87(2):286–9. doi:10.1097/TP.0b013e31819389cc.PubMedCrossRef

118.

Zarkhin V, Li L, Kambham N, Sigdel T, Salvatierra O, Sarwal MM. A randomized, prospective trial of rituximab for acute rejection in pediatric renal transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2008;8(12):2607–17. doi:10.1111/j.1600-6143.2008.02411.x.CrossRef

119.

Everly MJ, Everly JJ, Susskind B, Brailey P, Arend LJ, Alloway RR, et al. Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection. Transplantation. 2008;86(12):1754–61. doi:10.1097/TP.0b013e318190af83.PubMedCrossRef

120.

Everly MJ. A summary of bortezomib use in transplantation across 29 centers. Clin Transpl. 2009;323–37.

121.

Flechner SM, Fatica R, Askar M, Stephany BR, Poggio E, Koo A, et al. The role of proteasome inhibition with bortezomib in the treatment of antibody-mediated rejection after kidney-only or kidney-combined organ transplantation. Transplantation. 2010;90(12):1486–92. doi:10.1097/TP.0b013e3181fdd9b0.PubMedCrossRef

122.

Walsh RC, Everly JJ, Brailey P, Rike AH, Arend LJ, Mogilishetty G, et al. Proteasome inhibitor-based primary therapy for antibody-mediated renal allograft rejection. Transplantation. 2010;89(3):277–84. doi:10.1097/TP.0b013e3181c6ff8d.PubMedCrossRef

123.

Waiser J, Budde K, Schutz M, Liefeldt L, Rudolph B, Schonemann C, et al. Comparison between bortezomib and rituximab in the treatment of antibody-mediated renal allograft rejection. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2012;27(3):1246–51. doi:10.1093/ndt/gfr465.

124.

Lonze BE, Dagher NN, Simpkins CE, Locke JE, Singer AL, Segev DL, et al. Eculizumab, bortezomib and kidney paired donation facilitate transplantation of a highly sensitized patient without vascular access. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2010;10(9):2154–60. doi:10.1111/j.1600-6143.2010.03191.x.CrossRef

125.

Chandran S, Baxter-Lowe L, Olson JL, Tomlanovich SJ, Webber A. Eculizumab for the treatment of de novo thrombotic microangiopathy post simultaneous pancreas-kidney transplantation—a case report. Transplant Proc. 2011;43(5):2097–101. doi:10.1016/j.transproceed.2011.02.064.PubMedCrossRef

126.

Noone D, Al-Matrafi J, Tinckam K, Zipfel PF, Herzenberg AM, Thorner PS, et al. Antibody mediated rejection associated with complement factor h-related protein 3/1 deficiency successfully treated with eculizumab. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2012;12(9):2546–53. doi:10.1111/j.1600-6143.2012.04124.x.CrossRef

127.

Csapo Z, Benavides-Viveros C, Podder H, Pollard V, Kahan BD. Campath-1H as rescue therapy for the treatment of acute rejection in kidney transplant patients. Transplant Proc. 2005;37(5):2032–6. doi:10.1016/j.transproceed.2005.03.042.PubMedCrossRef

Title: Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management
Authors: Yolanda W. Ng
Manpreet Singh
Minnie M. Sarwal
Publication date: 01-04-2015
Publisher: Springer International Publishing
Published in: Drugs / Issue 5/2015
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-015-0369-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Antibody-Mediated Rejection in Pediatric Kidney Transplantation: Pathophysiology, Diagnosis, and Management

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2015

Sucroferric Oxyhydroxide: A Review in Hyperphosphataemia in Chronic Kidney Disease Patients Undergoing Dialysis

Lenvatinib: First Global Approval

Eltrombopag: A Review of Its Use in Patients with Severe Aplastic Anaemia

Erratum to: Abacavir/Dolutegravir/Lamivudine Single-Tablet Regimen: A Review of Its Use in HIV-1 Infection

Drug Therapy of Apparent Treatment-Resistant Hypertension: Focus on Mineralocorticoid Receptor Antagonists

Daclatasvir: A Review of Its Use in Adult Patients with Chronic Hepatitis C Virus Infection