Skip to main content
SpringerLink
Log in

Acute and Chronic Kidney Transplant Rejection in Adolescents: Causes and Treatment

  • Chapter
  • First Online:
Book cover Adolescents with Chronic Kidney Disease

  • 714 Accesses

Abstract

Adolescence is a time of exploration, biochemical and immunological transformation, emotional lability, and transition from childhood to adulthood. During this time, adolescent transplant recipients are vulnerable to poor kidney outcomes including the development of acute and chronic transplant rejection. This chapter will focus on the unique challenges that clinicians face when treating adolescent transplant recipients with particular attention to mechanism, diagnosis, and treatment of acute and chronic kidney transplant rejection.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Fernandez HE, Gjertson D, Date C, Choi IK, Ettenger RB, Tsai EW. Tacrolimus percent coefficient of variation as a marker of acute rejection associated with nonadherence in adolescent renal transplant recipients. Pediatr Transplant. 2011;15:135.

    Article  Google Scholar 

  2. Sellares 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.

    Article  CAS  PubMed  Google Scholar 

  3. Wiebe C, Nevins TE, Robiner WN, Thomas W, Matas AJ, Nickerson PW. The synergistic effect of class II HLA epitope-mismatch and nonadherence on acute rejection and graft survival. Am J Transplant. 2015;15(8):2197–202.

    Article  CAS  PubMed  Google Scholar 

  4. Foster BJ, Dahhou M, Zhang X, Platt RW, Samuel SM, Hanley JA. Association between age and graft failure rates in young kidney transplant recipients. Transplantation. 2011;92(11):1237–43.

    Article  PubMed  Google Scholar 

  5. Smith JM, Ho PL, McDonald RA. Renal transplant outcomes in adolescents: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant. 2002;6(6):493–9.

    Article  PubMed  Google Scholar 

  6. Van Arendonk KJ, James NT, Boyarsky BJ, Garonzik-Wang JM, Orandi BJ, Magee JC, et al. Age at graft loss after pediatric kidney transplantation: exploring the high-risk age window. Clin J Am Soc Nephrol. 2013;8(6):1019–26.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gubbels Bupp MR. Sex, the aging immune system, and chronic disease. Cell Immunol. 2015;294(2):102–10.

    Article  CAS  PubMed  Google Scholar 

  8. Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol. 2003;112(5):973–80.

    Article  PubMed  Google Scholar 

  9. Gourley TS, Wherry EJ, Masopust D, Ahmed R. Generation and maintenance of immunological memory. Semin Immunol. 2004;16(5):323–33.

    Article  CAS  PubMed  Google Scholar 

  10. IJspeert H, van Schouwenburg PA, van Zessen D, Pico-Knijnenburg I, Driessen GJ, Stubbs AP, et al. Evaluation of the antigen-experienced B-cell receptor repertoire in healthy children and adults. Front Immunol. 2016;7:410.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Hooper SR, Gerson AC, Butler RW, Gipson DS, Mendley SR, Lande MB, et al. Neurocognitive functioning of children and adolescents with mild-to-moderate chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(8):1824–30.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Galvan A, Hare TA, Parra CE, Penn J, Voss H, Glover G, et al. Earlier development of the accumbens relative to orbitofrontal cortex might underlie risk-taking behavior in adolescents. J Neurosci. 2006;26(25):6885–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Galvan A, Hare T, Voss H, Glover G, Casey BJ. Risk-taking and the adolescent brain: who is at risk? Dev Sci. 2007;10(2):F8–F14.

    Article  PubMed  Google Scholar 

  14. Somerville LH, Hare T, Casey BJ. Frontostriatal maturation predicts cognitive control failure to appetitive cues in adolescents. J Cogn Neurosci. 2011;23(9):2123–34.

    Article  PubMed  Google Scholar 

  15. Silverman MH, Jedd K, Luciana M. Neural networks involved in adolescent reward processing: an activation likelihood estimation meta-analysis of functional neuroimaging studies. NeuroImage. 2015;122:427–39.

    Article  PubMed  Google Scholar 

  16. Gipson DS, Hooper SR, Duquette PJ, Wetherington CE, Stellwagen KK, Jenkins TL, et al. Memory and executive functions in pediatric chronic kidney disease. Child Neuropsychol. 2006;12(6):391–405.

    Article  PubMed  Google Scholar 

  17. Haffner D, Nissel R. Growth and puberty in chronic kidney disease. In: Geary DF, Schaefer F, editors. Comprehensive pediatric nephrology. 1st ed. Philadelphia: Mosby Elsevier; 2008. p. 709–32.

    Chapter  Google Scholar 

  18. Rizzoni G, Broyer M, Brunner FP, Brynger H, Challah S, Kramer P, et al. Combined report on regular dialysis and transplantation of children in Europe, XIII, 1983. Proc Eur Dial Transplant Assoc Eur Ren Assoc. 1985;21:66–95.

    CAS  PubMed  Google Scholar 

  19. Haffner D, Zivicnjak M. Molecular and functional noninvasive immune monitoring in the ESCAPE study for prediction of subclinical renal allograft rejection. Pediatr Nephrol. 2017;32(6):949–64.

    Google Scholar 

  20. Nissel R, Brazda I, Feneberg R, Wigger M, Greiner C, Querfeld U, et al. Effect of renal transplantation in childhood on longitudinal growth and adult height. Kidney Int. 2004;66(2):792–800.

    Article  PubMed  Google Scholar 

  21. Tainio J, Qvist E, Vehmas R, Jahnukainen K, Holtta T, Valta H, et al. Pubertal development is normal in adolescents after renal transplantation in childhood. Transplantation. 2011;92(4):404–9.

    Article  PubMed  Google Scholar 

  22. Low MJ. Neuroendocrinology. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors. Williams textbook of endocrinology. 13th ed. Philadelphia: Elsevier; 2016. p. 109–75.

    Google Scholar 

  23. Ahn JJ, O’Mahony J, Moshkova M, Hanwell HE, Singh H, Zhang MA, et al. Puberty in females enhances the risk of an outcome of multiple sclerosis in children and the development of central nervous system autoimmunity in mice. Mult Scler. 2015;21(6):735–48.

    Article  PubMed  Google Scholar 

  24. Brenhouse HC, Schwarz JM. Immunoadolescence: neuroimmune development and adolescent behavior. Neurosci Biobehav Rev. 2016;70:288–99.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Liva SM, Voskuhl RR. Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production. J Immunol. 2001;167(4):2060–7.

    Article  CAS  PubMed  Google Scholar 

  26. Mingomataj EC, Bakiri AH. Regulator versus effector paradigm: interleukin-10 as indicator of the switching response. Clin Rev Allergy Immunol. 2016;50(1):97–113.

    Article  CAS  PubMed  Google Scholar 

  27. McDaniel DO, Rigney DA, McDaniel KY, Windham WJ, Redmond P, Williams B, et al. Early expression profile of inflammatory markers and kidney allograft status. Transplant Proc. 2013;45(4):1520–3.

    Article  CAS  PubMed  Google Scholar 

  28. Sabat R, Grutz G, Warszawska K, Kirsch S, Witte E, Wolk K, et al. Biology of interleukin-10. Cytokine Growth Factor Rev. 2010;21(5):331–44.

    Article  CAS  PubMed  Google Scholar 

  29. Studies NAPRTaC. North American Pediatric Renal Trials and Collaborative Studies 2014 Annual transplant report. 2014.

    Google Scholar 

  30. Male D, Brostoff J, Roth DB, Roitt IM. Transplantation and rejection. In: Hyde M, Vosburgh A, editors. Immunology. Philadelphia: Saunders Elsevier; 2013. p. 341–2.

    Chapter  Google Scholar 

  31. Dharnidharka VR, Fiorina P, Harmon WE. Kidney transplantation in children. N Engl J Med. 2014;371(6):549–58.

    Article  CAS  PubMed  Google Scholar 

  32. Tse G, Marson L. Immunology of graft rejection. In: Forsythe JL, editor. Transplantation. Philadelphia: Saunders Elsevier; 2014. p. 34–53.

    Google Scholar 

  33. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190(3):255–66.

    Article  CAS  PubMed  Google Scholar 

  34. Land W. Postischemic reperfusion injury to allografts – a case for ‘innate immunity’? Eur Surg Res. 2002;34(1–2):160–9.

    Article  CAS  PubMed  Google Scholar 

  35. Lopez-Neblina F, Toledo AH, Toledo-Pereyra LH. Molecular biology of apoptosis in ischemia and reperfusion. J Investig Surg. 2005;18(6):335–50.

    Article  Google Scholar 

  36. Tilney NL, Guttmann RD. Effects of initial ischemia/reperfusion injury on the transplanted kidney. Transplantation. 1997;64(7):945–7.

    Article  CAS  PubMed  Google Scholar 

  37. Lu CY, Winterberg PD, Chen J, Hartono JR. Acute kidney injury: a conspiracy of toll-like receptor 4 on endothelia, leukocytes, and tubules. Pediatr Nephrol. 2012;27(10):1847–54.

    Article  PubMed  Google Scholar 

  38. Briscoe DM, Alexander SI, Lichtman AH. Interactions between T lymphocytes and endothelial cells in allograft rejection. Curr Opin Immunol. 1998;10(5):525–31.

    Article  CAS  PubMed  Google Scholar 

  39. Kim IK, Bedi DS, Denecke C, Ge X, Tullius SG. Impact of innate and adaptive immunity on rejection and tolerance. Transplantation. 2008;86(7):889–94.

    Article  CAS  PubMed  Google Scholar 

  40. Colvin RB. Antibody-mediated renal allograft rejection: diagnosis and pathogenesis. J Am Soc Nephrol. 2007;18(4):1046–56.

    Article  CAS  PubMed  Google Scholar 

  41. Linfert D, Chowdhry T, Rabb H. Lymphocytes and ischemia-reperfusion injury. Transplant Rev (Orlando). 2009;23(1):1–10.

    Article  Google Scholar 

  42. Boros P, Bromberg JS. New cellular and molecular immune pathways in ischemia/reperfusion injury. Am J Transplant. 2006;6(4):652–8.

    Article  CAS  PubMed  Google Scholar 

  43. Mitchell P, Afzali B, Lombardi G, Lechler RI. The T helper 17-regulatory T cell axis in transplant rejection and tolerance. Curr Opin Organ Transplant. 2009;14(4):326–31.

    Article  PubMed  Google Scholar 

  44. Alegre ML, Leemans J, Le Moine A, Florquin S, De Wilde V, Chong A, et al. The multiple facets of toll-like receptors in transplantation biology. Transplantation. 2008;86(1):1–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cardinal H, Dieude M, Hebert MJ. The emerging importance of non-HLA autoantibodies in kidney transplant complications. J Am Soc Nephrol. 2017;28(2):400–6.

    Article  CAS  PubMed  Google Scholar 

  46. Dikdan GS, Mora-Esteves C, Koneru B. Review of randomized clinical trials of donor management and organ preservation in deceased donors: opportunities and issues. Transplantation. 2012;94(5):425–41.

    Article  PubMed  Google Scholar 

  47. Zheng X, Zang G, Jiang J, He W, Johnston NJ, Ling H, et al. Attenuating ischemia-reperfusion injury in kidney transplantation by perfusing donor organs with siRNA cocktail solution. Transplantation. 2016;100(4):743–52.

    Article  CAS  PubMed  Google Scholar 

  48. Rogers NM, Zhang ZJ, Wang JJ, Thomson AW, Isenberg JS. CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion. Kidney Int. 2016;90(2):334–47.

    Article  CAS  PubMed  Google Scholar 

  49. Benichou G, Thomson AW. Direct versus indirect allorecognition pathways: on the right track. Am J Transplant. 2009;9(4):655–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. NCBI. NIH. 2016. Available from: https://www.ncbi.nlm.nih.gov/gene/.

  51. Benichou G, Valujskikh A, Heeger PS. Contributions of direct and indirect T cell alloreactivity during allograft rejection in mice. J Immunol. 1999;162(1):352–8.

    CAS  PubMed  Google Scholar 

  52. Marino J, Paster J, Benichou G. Allorecognition by T lymphocytes and allograft rejection. Front Immunol. 2016;7:582.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Herrera OB, Golshayan D, Tibbott R, Ochoa FS, James MJ, Marelli-Berg FM, et al. A novel pathway of alloantigen presentation by dendritic cells. J Immunol. 2004;173(8):4828–37.

    Article  CAS  PubMed  Google Scholar 

  54. Ingulli E. Mechanism of cellular rejection in transplantation. Pediatr Nephrol. 2010;25(1):61–74.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Bach F, Hirschhorn K. Lymphocyte interaction: a potential histocompatibility test in vitro. Science. 1964;143(3608):813–4.

    Article  CAS  PubMed  Google Scholar 

  56. Kaye J, Hedrick SM. Analysis of specificity for antigen, Mls, and allogenic MHC by transfer of T-cell receptor alpha- and beta-chain genes. Nature. 1988;336(6199):580–3.

    Article  CAS  PubMed  Google Scholar 

  57. Daniel C, Horvath S, Allen PM. A basis for alloreactivity: MHC helical residues broaden peptide recognition by the TCR. Immunity. 1998;8(5):543–52.

    Article  CAS  PubMed  Google Scholar 

  58. Weber DA, Terrell NK, Zhang Y, Strindberg G, Martin J, Rudensky A, et al. Requirement for peptide in alloreactive CD4+ T cell recognition of class II MHC molecules. J Immunol. 1995;154(10):5153–64.

    CAS  PubMed  Google Scholar 

  59. Lechler RI, Batchelor JR. Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med. 1982;155(1):31–41.

    Article  CAS  PubMed  Google Scholar 

  60. Ali JM, Bolton EM, Bradley JA, Pettigrew GJ. Allorecognition pathways in transplant rejection and tolerance. Transplantation. 2013;96(8):681–8.

    Article  CAS  PubMed  Google Scholar 

  61. Halloran PF. Immunosuppressive drugs for kidney transplantation. New Engl J Med. 2004;351(26):2715–29.

    Article  CAS  PubMed  Google Scholar 

  62. Nankivell BJ, Alexander SI. Rejection of the kidney allograft. N Engl J Med. 2010;363(15):1451–62.

    Article  CAS  PubMed  Google Scholar 

  63. Baliga P, Chavin KD, Qin L, Woodward J, Lin J, Linsley PS, et al. CTLA4Ig prolongs allograft survival while suppressing cell-mediated immunity. Transplantation. 1994;58(10):1082–90.

    Article  CAS  PubMed  Google Scholar 

  64. Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity. 1996;4(6):535–43.

    Article  CAS  PubMed  Google Scholar 

  65. Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, et al. Reversal of the TCR stop signal by CTLA-4. Science. 2006;313(5795):1972–5.

    Article  CAS  PubMed  Google Scholar 

  66. Schneider H, Smith X, Liu H, Bismuth G, Rudd CE. CTLA-4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times and calcium mobilization. Eur J Immunol. 2008;38(1):40–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Garside P, Ingulli E, Merica RR, Johnson JG, Noelle RJ, Jenkins MK. Visualization of specific B and T lymphocyte interactions in the lymph node. Science. 1998;281(5373):96–9.

    Article  CAS  PubMed  Google Scholar 

  68. Linsley PS, Wallace PM, Johnson J, Gibson MG, Greene JL, Ledbetter JA, et al. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science. 1992;257(5071):792–5.

    Article  CAS  PubMed  Google Scholar 

  69. Kirk AD, Harlan DM, Armstrong NN, Davis TA, Dong Y, Gray GS, et al. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci U S A. 1997;94(16):8789–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity. 1994;1(9):793–801.

    Article  CAS  PubMed  Google Scholar 

  71. Larsen CP, Pearson TC, Adams AB, Tso P, Shirasugi N, Strobert E, et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant. 2005;5(3):443–53.

    Article  CAS  PubMed  Google Scholar 

  72. Charpentier B, Medina Pestana JO, Del CRM, Rostaing L, Grinyo J, Vanrenterghem Y, et al. Long-term exposure to belatacept in recipients of extended criteria donor kidneys. Am J Transplant. 2013;13(11):2884–91.

    Article  CAS  PubMed  Google Scholar 

  73. Rostaing L, Vincenti F, Grinyo J, Rice KM, Bresnahan B, Steinberg S, et al. Long-term belatacept exposure maintains efficacy and safety at 5 years: results from the long-term extension of the BENEFIT study. Am J Transplant. 2013;13(11):2875–83.

    Article  CAS  PubMed  Google Scholar 

  74. Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, et al. Belatacept and long-term outcomes in kidney transplantation. N Engl J Med. 2016;374(4):333–43.

    Article  CAS  PubMed  Google Scholar 

  75. Lerch C, Kanzelmeyer NK, Ahlenstiel-Grunow T, Froede K, Kreuzer M, Drube J, et al. Belatacept after kidney transplantation in adolescents: a retrospective study. Transpl Int. 2017;30(5):494–501.

    Article  CAS  PubMed  Google Scholar 

  76. Chopra B, Sureshkumar KK. Co-stimulatory blockade with belatacept in kidney transplantation. Expert Opin Biol Ther. 2014;14(5):563–7.

    Article  CAS  PubMed  Google Scholar 

  77. Grinyo J, Charpentier B, Pestana JM, Vanrenterghem Y, Vincenti F, Reyes-Acevedo R, et al. An integrated safety profile analysis of belatacept in kidney transplant recipients. Transplantation. 2010;90(12):1521–7.

    Article  PubMed  Google Scholar 

  78. Okimura K, Maeta K, Kobayashi N, Goto M, Kano N, Ishihara T, et al. Characterization of ASKP1240, a fully human antibody targeting human CD40 with potent immunosuppressive effects. Am J Transplant. 2014;14(6):1290–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Ma A, Dun H, Song L, Hu Y, Zeng L, Bai J, et al. Pharmacokinetics and pharmacodynamics of ASKP1240, a fully human anti-CD40 antibody, in normal and renal transplanted Cynomolgus monkeys. Transplantation. 2014;97(4):397–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wang D, Matsumoto R, You Y, Che T, Lin XY, Gaffen SL, et al. CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of protein kinase C-theta, Bcl10, and IkappaB kinase beta to the immunological synapse through CARMA1. Mol Cell Biol. 2004;24(1):164–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Shapiro R, Zeevi A, Basu A, Tan HP, Kayler LK, Blisard DM, et al. Alemtuzumab preconditioning with tacrolimus monotherapy-the impact of serial monitoring for donor-specific antibody. Transplantation. 2008;85(8):1125–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tan HP, Kaczorowski D, Basu A, McCauley J, Marcos A, Donaldson J, et al. Steroid-free tacrolimus monotherapy after pretransplantation thymoglobulin or Campath and laparoscopy in living donor renal transplantation. Transplant Proc. 2005;37(10):4235–40.

    Article  CAS  PubMed  Google Scholar 

  83. Shapiro R, Basu A, Tan H, Gray E, Kahn A, Randhawa P, et al. Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath. J Am Coll Surg. 2005;200(4):505–15. quiz A59–61

    Article  PubMed  PubMed Central  Google Scholar 

  84. Sung J, Barry JM, Jenkins R, Rozansky D, Iragorri S, Conlin M, et al. Alemtuzumab induction with tacrolimus monotherapy in 25 pediatric renal transplant recipients. Pediatr Transplant. 2013;17(8):718–25.

    Article  CAS  PubMed  Google Scholar 

  85. Supe-Markovina K, Melquist JJ, Connolly D, DiCarlo HN, Waltzer WC, Fine RN, et al. Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: a seven-yr experience. Pediatr Transplant. 2014;18(4):363–8.

    Article  CAS  PubMed  Google Scholar 

  86. Kaabak MM, Babenko NN, Samsonov DV, Sandrikov VA, Maschan AA, Zokoev AK. Alemtuzumab induction in pediatric kidney transplantation. Pediatr Transplant. 2013;17(2):168–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Crowson CN, Reed RD, Shelton BA, MacLennan PA, Locke JE. Lymphocyte-depleting induction therapy lowers the risk of acute rejection in African American pediatric kidney transplant recipients. Pediatr Transplant. 2017;21(1):e12823.

    Article  CAS  Google Scholar 

  88. Akalin E, Hendrix RC, Polavarapu RG, Pearson TC, Neylan JF, Larsen CP, et al. Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology. Transplantation. 2001;72(5):948–53.

    Article  CAS  PubMed  Google Scholar 

  89. Hoffmann SC, Hale DA, Kleiner DE, Mannon RB, Kampen RL, Jacobson LM, et al. Functionally significant renal allograft rejection is defined by transcriptional criteria. Am J Transplant. 2005;5(3):573–81.

    Article  CAS  PubMed  Google Scholar 

  90. Barry M, Bleackley RC. Cytotoxic T lymphocytes: all roads lead to death. Nat Rev Immunol. 2002;2(6):401–9.

    Article  CAS  PubMed  Google Scholar 

  91. Bradley JA, Mason DW, Morris PJ. Evidence that rat renal allografts are rejected by cytotoxic T cells and not by nonspecific effectors. Transplantation. 1985;39(2):169–75.

    Article  CAS  PubMed  Google Scholar 

  92. Al-Lamki RS, Wang J, Skepper JN, Thiru S, Pober JS, Bradley JR. Expression of tumor necrosis factor receptors in normal kidney and rejecting renal transplants. Lab Investig. 2001;81(11):1503–15.

    Article  CAS  PubMed  Google Scholar 

  93. Kwun J, Manook M, Page E, Burghuber C, Hong J, Knechtle SJ. Crosstalk between T and B cells in the germinal center after transplantation. Transplantation. 2017;101(4):704–12.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Ng YW, Singh M, Sarwal MM. Antibody-mediated rejection in pediatric kidney transplantation: pathophysiology, diagnosis, and management. Drugs. 2015;75(5):455–72.

    Article  CAS  PubMed  Google Scholar 

  95. Sarwal M, Chua MS, Kambham N, Hsieh SC, 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.

    Article  CAS  PubMed  Google Scholar 

  96. Zarkhin V, Kambham N, Li L, Kwok S, Hsieh SC, Salvatierra O, et al. Characterization of intra-graft B cells during renal allograft rejection. Kidney Int. 2008;74(5):664–73.

    Article  CAS  PubMed  Google Scholar 

  97. Terasaki PI. Humoral theory of transplantation. Am J Transplant. 2003;3(6):665–73.

    Article  PubMed  Google Scholar 

  98. Alegre ML, Florquin S, Goldman M. Cellular mechanisms underlying acute graft rejection: time for reassessment. Curr Opin Immunol. 2007;19(5):563–8.

    Article  CAS  PubMed  Google Scholar 

  99. Bhatti AB, Usman M. Chronic renal transplant rejection and possible anti-proliferative drug targets. Cureus. 2015;7(11):e376.

    PubMed  PubMed Central  Google Scholar 

  100. Tsai EW, Rianthavorn P, Gjertson DW, Wallace WD, Reed EF, Ettenger RB. CD20+ lymphocytes in renal allografts are associated with poor graft survival in pediatric patients. Transplantation. 2006;82(12):1769–73.

    Article  PubMed  Google Scholar 

  101. Tsai EW, Wallace WD, Gjertson DW, Reed EF, Ettenger RB. Significance of intragraft CD138+ lymphocytes and p-S6RP in pediatric kidney transplant biopsies. Transplantation. 2010;90(8):875–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Durkan AM, Robinson LA. Acute allograft dysfunction. In: Geary DF, Schaefer F, editors. Comprehensive pediatric nephrology. 1st ed. Philadelphia: Mosby Elsevier; 2008. p. 931–45.

    Chapter  Google Scholar 

  103. Goldberg RJ, Weng FL, Kandula P. Acute and chronic allograft dysfunction in kidney transplant recipients. Med Clin N Am. 2016;100(3):487–503.

    Article  PubMed  Google Scholar 

  104. Crespo E, Roedder S, Sigdel T, Hsieh SC, Luque S, Cruzado JM, Tran TQ, Grinyó JM, Sarwal MM, Bestard O. Relationship among viremia/viral Infection, alloimmunity, and nutritional parameters in the first year after pediatric kidney transplantation. Transplantation. 2017;101(6):1400–9.

    Article  CAS  PubMed  Google Scholar 

  105. 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.

    Article  CAS  PubMed  Google Scholar 

  106. 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.

    Article  CAS  PubMed  Google Scholar 

  107. Loupy A, Haas M, Solez K, Racusen L, Glotz D, Seron D, et al. The Banff 2015 kidney meeting report: current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant. 2017;17(1):28–41.

    Article  CAS  PubMed  Google Scholar 

  108. Gray D, Shepherd H, Daar A, Oliver DO, Morris PJ. Oral versus intravenous high-dose steroid treatment of renal allograft rejection. The big shot or not? Lancet. 1978;1(8056):117–8.

    Article  CAS  PubMed  Google Scholar 

  109. Vineyard GC, Fadem SZ, Dmochowski J, Carpenter CB, Wilson RE. Evaluation of corticosteroid therapy for acute renal allograft rejection. Surg Gynecol Obstet. 1974;138(2):225–9.

    CAS  PubMed  Google Scholar 

  110. Kidney Disease: Improving Global Outcomes Transplant Work G. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(Suppl 3):S1–155.

    Google Scholar 

  111. Webster AC, Pankhurst T, Rinaldi F, Chapman JR, Craig JC. Monoclonal and polyclonal antibody therapy for treating acute rejection in kidney transplant recipients: a systematic review of randomized trial data. Transplantation. 2006;81(7):953–65.

    Article  CAS  PubMed  Google Scholar 

  112. Upadhyay K, Midgley L, Moudgil A. Safety and efficacy of alemtuzumab in the treatment of late acute renal allograft rejection. Pediatr Transplant. 2012;16(3):286–93.

    Article  CAS  PubMed  Google Scholar 

  113. van den Hoogen MW, Hesselink DA, van Son WJ, Weimar W, Hilbrands LB. Treatment of steroid-resistant acute renal allograft rejection with alemtuzumab. Am J Transplant. 2013;13(1):192–6.

    Article  PubMed  CAS  Google Scholar 

  114. Ettenger R, Chin H, Kesler K, Bridges N, Grimm P, Reed EF, Sarwal M, Sibley R, Tsai E, Warshaw B, Kirk AD. Relationship among viremia/viral infection, alloimmunity, and nutritional parameters in the first year after pediatric kidney transplantation. Am J Transplant. 2016;17(6):1549–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Rees L, Kim JJ. HLA sensitisation: can it be prevented? Pediatr Nephrol. 2015;30(4):577–87.

    Article  PubMed  Google Scholar 

  116. Pizzo HP, Ettenger RB, Gjertson DW, Reed EF, Zhang J, Gritsch HA, et al. Sirolimus and tacrolimus coefficient of variation is associated with rejection, donor-specific antibodies, and nonadherence. Pediatr Nephrol. 2016;31(12):2345–52.

    Article  PubMed  Google Scholar 

  117. 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. 2015;26(2):457–67.

    Article  PubMed  CAS  Google Scholar 

  118. Sutherland SM, Chen G, Sequeira FA, Lou CD, Alexander SR, Tyan DB. Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss. Pediatr Transplant. 2012;16(1):12–7.

    Article  CAS  PubMed  Google Scholar 

  119. Dragun D, Catar R, Philippe A. Non-HLA antibodies against endothelial targets bridging allo- and autoimmunity. Kidney Int. 2016;90(2):280–8.

    Article  CAS  PubMed  Google Scholar 

  120. Zhang Q, Reed EF. The importance of non-HLA antibodies in transplantation. Nat Rev Nephrol. 2016;12(8):484–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Webb NJ, Maxwell H. Chronic renal transplant dysfunction. In: Geary DF, Schaefer F, editors. Comprehensive pediatric nephrology. 1st ed. Philadelphia: Mosby Elsevier; 2008. p. 947–65.

    Chapter  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  123. 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. 2003;3(6):708–14.

    Article  PubMed  Google Scholar 

  124. Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, et al. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014;14(2):272–83.

    Article  CAS  PubMed  Google Scholar 

  125. Wiebe C, Pochinco D, Blydt-Hansen TD, Ho J, Birk PE, Karpinski M, et al. Class II HLA epitope matching-A strategy to minimize de novo donor-specific antibody development and improve outcomes. Am J Transplant. 2013;13(12):3114–22.

    Article  CAS  PubMed  Google Scholar 

  126. Gralla J, Tong S, Wiseman AC. The impact of human leukocyte antigen mismatching on sensitization rates and subsequent retransplantation after first graft failure in pediatric renal transplant recipients. Transplantation. 2013;95(10):1218–24.

    Article  CAS  PubMed  Google Scholar 

  127. Xu H, Samy KP, Guasch A, Mead SI, Ghali A, Mehta A, et al. Postdepletion lymphocyte reconstitution during belatacept and rapamycin treatment in kidney transplant recipients. Am J Transplant. 2016;16(2):550–64.

    Article  CAS  PubMed  Google Scholar 

  128. Kirk AD, Guasch A, Xu H, Cheeseman J, Mead SI, Ghali A, et al. Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors. Am J Transplant. 2014;14(5):1142–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Henriksson J, Tyden G, Hoijer J, Wadstrom JA. Prospective randomized trial on the effect of using an electronic monitoring drug dispensing device to improve adherence and compliance. Transplantation. 2016;100(1):203–9.

    Article  CAS  PubMed  Google Scholar 

  130. Kreuzer M, Prufe J, Bethe D, Vogel C, Grosshennig A, Koch A, et al. The TRANSNephro-study examining a new transition model for post-kidney transplant adolescents and an analysis of the present health care: study protocol for a randomized controlled trial. Trials. 2014;15:505.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Browning RB, McGillicuddy JW, Treiber FA, Taber DJ. Kidney transplant recipients’ attitudes about using mobile health technology for managing and monitoring medication therapy. J Am Pharm Assoc (2003). 2016;56(4):450–4. e1

    Article  Google Scholar 

  132. Bonomini V, Vangelista A, Frasca GM, Di Felice A, Liviano D’Arcangelo G. Effects of plasmapheresis in renal transplant rejection. A controlled study. Trans Am Soc Artif Intern Organs. 1985;31:698–703.

    CAS  PubMed  Google Scholar 

  133. 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.

    Article  CAS  PubMed  Google Scholar 

  134. 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.

    Article  CAS  PubMed  Google Scholar 

  135. 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. 2008;8(12):2607–17.

    Article  CAS  PubMed  Google Scholar 

  136. 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. 2013;11(5):404–7.

    Article  PubMed  Google Scholar 

  137. Pearl MH. Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection. Pediatric Nephrology. 2016;31(8):1341–8.

    Article  PubMed  Google Scholar 

  138. 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.

    Article  CAS  PubMed  Google Scholar 

  139. Sautenet B, Blancho G, Buchler M, Morelon E, Toupance O, Barrou B, et al. One-year results of the effects of rituximab on acute antibody-mediated rejection in renal transplantation: RITUX ERAH, a multicenter double-blind randomized placebo-controlled trial. Transplantation. 2016;100(2):391–9.

    Article  CAS  PubMed  Google Scholar 

  140. 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.

    Article  CAS  PubMed  Google Scholar 

  141. Gulleroglu K, Baskin E, Moray G, Ozdemir H, Arslan H, Haberal M. Rituximab therapy and infection risk in pediatric renal transplant patients. Exp Clin Transplant. 2016;14(2):172–5.

    PubMed  Google Scholar 

  142. Kizilbash S, Claes D, Ashoor I, Chen A, Jandeska S, Matar RB, et al. Bortezomib in the treatment of antibody-mediated rejection in pediatric kidney transplant recipients: a multicenter Midwest Pediatric Nephrology Consortium study. Pediatr Transplant. 2017;21(3):e12873.

    Article  CAS  Google Scholar 

  143. Choi J, Aubert O, Vo A, Loupy A, Haas M, Puliyanda D, et al. Assessment of tocilizumab (anti-interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant glomerulopathy in HLA-sensitized renal allograft recipients. Am J Transplant. 2017;17:2381–9.

    Article  CAS  PubMed  Google Scholar 

  144. Kim I, Wu G, Chai NN, Klein AS, Jordan S. Anti-interleukin 6 receptor antibodies attenuate antibody recall responses in a mouse model of allosensitization. Transplantation. 2014;98(12):1262–70.

    Article  CAS  PubMed  Google Scholar 

  145. 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.

    Article  CAS  PubMed  Google Scholar 

  146. 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.

    Article  PubMed  Google Scholar 

  147. 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.

    Article  PubMed  Google Scholar 

  148. 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. 2009;9(1):231–5.

    Article  CAS  PubMed  Google Scholar 

  149. Cornell LD, Schinstock CA, Gandhi MJ, Kremers WK, Stegall MD. Positive crossmatch kidney transplant recipients treated with eculizumab: outcomes beyond 1 year. Am J Transplant. 2015;15(5):1293–302.

    Article  CAS  PubMed  Google Scholar 

  150. Montgomery RA, Orandi BJ, Racusen L, Jackson AM, Garonzik-Wang JM, Shah T, et al. Plasma-derived C1 esterase inhibitor for acute antibody-mediated rejection following kidney transplantation: results of a randomized double-blind placebo-controlled pilot study. Am J Transplant. 2016;16:3468–78.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Duke University Medical Center, Durham, NC, USA

    Jonathan H. Pelletier, Emeraghi E. David, Annabelle N. Chua & Eileen Tsai Chambers

Authors
  1. Jonathan H. Pelletier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emeraghi E. David
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annabelle N. Chua
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eileen Tsai Chambers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan H. Pelletier .

Editor information

Editors and Affiliations

  1. Department of Pediatric Nephrology, UC Davis Medical Center, Sacramento, CA, USA

    Maha N. Haddad

  2. Department of Pediatrics, Division of Nephrology, University of California San Francisco, San Francisco, CA, USA

    Erica Winnicki

  3. Department of Pediatrics, UC Davis Children’s Hospital, Sacramento, CA, USA

    Stephanie Nguyen

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pelletier, J.H., David, E.E., Chua, A.N., Chambers, E.T. (2019). Acute and Chronic Kidney Transplant Rejection in Adolescents: Causes and Treatment. In: Haddad, M., Winnicki, E., Nguyen, S. (eds) Adolescents with Chronic Kidney Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-97220-6_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-97220-6_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-97219-0

  • Online ISBN: 978-3-319-97220-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation