Late Allograft Loss of Function: Recurrence of Disease, Chronic Allograft Injury (Immune and Nonimmune Mediated), and Retransplantation

  • H. Jorge Baluarte
  • Jo Ann Palmer
Reference work entry
Part of the Organ and Tissue Transplantation book series (OTT)


Renal transplantation is accepted as the treatment of choice for children with end-stage renal disease (ESRD). Over the past decade, improved short-term graft survival has been observed in children and adults with kidney transplantation; however, long-term survival has not improved. The causes of renal allograft dysfunction vary with the time after transplantation. Slowly progressive renal disease that occurs over a period of years after renal transplantation most commonly results from chronic allograft injury, calcineurin inhibitor toxicity, hypertensive nephrosclerosis, viral infections, and recurrent or de novo renal disease. Preventable causes of late allograft failure are important to identify in order to improve the long-term successful outcome of allograft survival. Retransplantation in the pediatric population is likely to be common into adulthood. Primary reasons for late allograft failure will impact the success of retransplantation.


Chronic allograft nephropathy Chronic kidney disease Antibody-mediated rejection Focal segmental glomerulosclerosis recurrence Proteinuria Calcineurin inhibitor toxicity Donor-specific antibodies Allograft nephrectomy BK nephropathy Retransplantation 


  1. Ahmad N, Ahmed K, Mamode N (2009) Does nephrectomy of failed allograft influence graft survival after re-transplantation? Nephrol Dial Transplant 24:639–642CrossRefPubMedGoogle Scholar
  2. Akoh JA (2011) Transplant nephrectomy. World J Transplant 1(1):4–12CrossRefPubMedPubMedCentralGoogle Scholar
  3. Artero ML, Sharma R, Savin VJ et al (1994) Plasmapheresis reduces proteinuria and serum capacity to injure glomeruli in patients with recurrent focal glomerulosclerosis. Am J K Dis 23(4):574–581CrossRefGoogle Scholar
  4. Baluarte HJ, Palmer JA, Lopez S et al (2011) Recurrence of Focal Segmental Glomerulosclerosis (FSGS) in children after renal transplantation. Pediatr Transplant 15(Suppl 1):25Google Scholar
  5. Bennet WM (2005) The failed renal transplant: in or out? Semin Dial 18:18–189CrossRefGoogle Scholar
  6. Bergstralh EJ, Monico CG, Lieske JC et al (2010) Transplantation outcomes in primary hyperoxaluria. Am J Transplant 10(11):2493–2501CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bomback AS, Smith RJ, Barile GR et al (2012) Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol 7(5):748–756CrossRefPubMedPubMedCentralGoogle Scholar
  8. Canaud G, Zuber J, Sberro R et al (2009) Intensive and prolonged treatment of focal and segmental glomerulosclerosis recurrence in adult kidney transplant recipients: a pilot study. Am J Transplant 9(5):1081–1086CrossRefPubMedGoogle Scholar
  9. Chaudhuri A, Ozawa M, Everly MJ et al (2013) The clinical impact of humoral immunity in pediatric renal transplantation. J Am Soc Nephrol 24(4):655–664CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cheong HI, Han HW, Park HW et al (2000) Early recurrent nephrotic syndrome after renal transplantation in children with focal segmental glomerulosclerosis. Nephrol Dial Transplant 15(1):78–81CrossRefPubMedGoogle Scholar
  11. Cochat P, Fargue S, Mestrallet G et al (2009) Disease recurrence in paediatric renal transplantation. Pediatr Nephrol 24(11):2097–2108CrossRefPubMedPubMedCentralGoogle Scholar
  12. Cornell LD, Colvin RB (2005) Chronic allograft nephropathy. Curr Opin Nephrol Hypertens 14(3):229–234CrossRefPubMedGoogle Scholar
  13. Dall’Amico R, Ghiggeri G, Carraro M et al (1999) Prediction and treatment of recurrent focal segmental glomerulosclerosis after renal transplantation in children. Am J Kidney Dis 34(6):1048–1055CrossRefPubMedGoogle Scholar
  14. Dantal J, Bigot E, Bogers W et al (1994) Effect of plasma protein adsorption on protein excretion in kidney transplant recipients with recurrent nephrotic syndrome. N Engl J Med 330(1):7–14CrossRefPubMedGoogle Scholar
  15. Dharnidharka VR, Cherikh WS, Neff R et al (2010) Re-transplantation after BK virus nephropathy in prior kidney transplant: an OPTN data base analysis. Am J Transplant 2010(10):1312–1315CrossRefGoogle Scholar
  16. Dharnidharka VR, Fiorina P, Harmon WE (2014) Kidney transplantation in children. N Engl J Med 371(6):549–558CrossRefPubMedGoogle Scholar
  17. Farney AC, Matas AJ, Noreen HJ et al (1996) Does re-exposure to mismatched HLA antigens decrease renal re-transplant allograft survival? Clin Transplant 10(2):147–156PubMedGoogle Scholar
  18. Fine RN (1985) Renal transplantation for children – the only realistic choice. Kidney Int Suppl 17:S15–S17PubMedGoogle Scholar
  19. Fine RN (2007) Recurrence of nephrotic syndrome/focal segmental glomerulosclerosis following renal transplantation in children. Pediatr Nephrol 22:496–502CrossRefPubMedGoogle Scholar
  20. Fuentes GM, Mesenguer CG, Carrion AP (2010) Long term outcome of focal segmental glomerulosclerosis after pediatric renal transplantation. Pediatr Nephrol 25(3):529–534CrossRefPubMedGoogle Scholar
  21. Geetha D, Sozio SM, Ghanta M et al (2011) Results of repeat renal transplantation after graft loss from BK nephropathy. Transplantation 92(7):781–786CrossRefPubMedGoogle Scholar
  22. Genevri F, Pastorino N, de Santis R et al (2003) Retransplantation after kidney graft loss due to polyoma BK virus nephropathy: successful outcomes without allograft nephropathy. Am J Kidney Dis 42(4):821–825CrossRefGoogle Scholar
  23. Goldfarb-Rumyantzev A, Hurdle J, Baird B et al (2006) The role of pre-emptive re-transplant in graft and recipient outcome. Nephrol Dial Transplant 21:1355–1364CrossRefPubMedGoogle Scholar
  24. Gregoor PJ, Kramer P, Weimar W et al (1997) Infections after renal allograft failure in patients with or without low-dose maintenance immunosuppression. Transplantation 63(10):1528–1530CrossRefPubMedGoogle Scholar
  25. Groothoff JW, Cransberg K, Offringa M et al (2004) Long term follow up of renal transplantation in children: a Dutch cohort study. Transplantation 78(3):453–460CrossRefPubMedGoogle Scholar
  26. Guyot C, Nguyen JM, Cochat P et al (1996) Risk factors for chronic rejection in pediatric renal allograft recipients. Pediatr Nephrol 10(6):723–727CrossRefPubMedGoogle Scholar
  27. Haas M, Sis B, Racusen LC et al (2014) Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 14(2):272–283CrossRefPubMedGoogle Scholar
  28. Hariharan S, Adams MB, Brennan DC et al (1999) Recurrent and de novo glomerular disease after renal transplantation; a report from Renal Allograft Disease Registry (RADR). Transplantation 68(5):635–641CrossRefPubMedGoogle Scholar
  29. Hickson LJ, Gera M, Amer H et al (2009) Kidney transplantation for primary focal segmental glomerulosclerosis: outcomes and response to therapy for recurrence. Transplantation 87(8):1232–1239CrossRefPubMedGoogle Scholar
  30. Icard P, Hooper BR, Gipson DS et al (2010) Cognitive improvement in children with CKD after transplant. Pediatr Transplant 14(14):887–890CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kashtan CE (2006) Renal transplantation in patients with Alport syndrome. Pediatr Transplant 10(6):651–657CrossRefPubMedGoogle Scholar
  32. Kotanko P, Pusey CD, Levy JB (1997) Recurrent glomerulonephritis following renal transplantation. Transplantation 63(8):1045–1052CrossRefPubMedGoogle Scholar
  33. Loirat C, Niaudet P (2003) The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children. Pediatr Nephrol 18(11):1095–1101CrossRefPubMedGoogle Scholar
  34. McDonald SP, Craig JC (2004) Long term survival of children with end stage renal disease. N Engl J Med 350(26):2654–2662CrossRefPubMedGoogle Scholar
  35. Melk A, Gourishankar S, Halloran PF (2002) Long-term effects of nonimmune tissue injury in renal transplantation. Curr Opin Organ Transplant 7:171–177CrossRefGoogle Scholar
  36. Miner JH, Baigent C, Flinter F et al (2014) The 2014 international workshop on Alport syndrome. Kidney Int 86(4):679–684CrossRefPubMedPubMedCentralGoogle Scholar
  37. Monteverde ML, Chaparro A, Goldberg J et al (2015) Donor specific anti-HLA antibodies in pediatric renal transplant recipients with creeping creatinine: prevalence, histological correlations, and impact on patient and graft survival. Pediatr Transplant 9:684–690CrossRefGoogle Scholar
  38. Moroni G, Longhi S, Quaglini S et al (2013) The long-term outcome of renal transplantation of IgA nephropathy and the impact of recurrence on graft survival. Nephrol Dial Transplant 28(5):1305–1314CrossRefPubMedGoogle Scholar
  39. Nankivell BJ, Kuypers DR (2011) Diagnosis and prevention of chronic kidney allograft loss. Lancet 378(9800):1428–1437CrossRefPubMedGoogle Scholar
  40. Nankivell BJ, Borrows RJ, Fung CL et al (2003) The natural history of chronic allograft nephropathy. N Engl J Med 349:2326–2333CrossRefPubMedGoogle Scholar
  41. NAPRTCS (2014) Annual transplant report. Available at Accessed 29 Oct 2015
  42. OPTN/SRTR (2012) Annual data report. Accessed 1 Sept 2015
  43. Pape L, Becker JV, Immenscherh S et al (2015) Acute and chronic antibody-mediated rejection in pediatric kidney transplantation. Pediatr Nephrol 30:417–424CrossRefPubMedGoogle Scholar
  44. Perseghin P, Capra M, Baldini V et al (2001) Bradykinin production during plasmapheresis procedures. Vox Sang 81(1):24–28CrossRefPubMedGoogle Scholar
  45. Peruzzi L, Amore A, Copo R (2014) Challenges in pediatric renal transplantation. World J Transplant 4(4):222–228CrossRefPubMedPubMedCentralGoogle Scholar
  46. Pickering MC, D’Agati VD, Nester CM et al (2013) C3 glomerulopathy: consensus report. Kidney Int 84(6):1079–1089CrossRefPubMedPubMedCentralGoogle Scholar
  47. Pradhan M, Petro J, Palmer J et al (2003) Early use of plasmapheresis for recurrent post-transplant FSGS. Pediatr Nephrol 18:934–938CrossRefPubMedGoogle Scholar
  48. Saland J (2014) Liver-kidney transplantation to cure atypical HUS: still an option post-eculizumab? Pediatr Nephrol 29(3):329–332CrossRefPubMedGoogle Scholar
  49. Savin VJ, Sharma R, Sharma M et al (1996) Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 334(14):878–883CrossRefPubMedGoogle Scholar
  50. Scheinman JI (2010) Liver transplantation in oxalosis prior to advanced chronic kidney disease. Pediatr Nephrol 25(11):2217–2222CrossRefPubMedGoogle Scholar
  51. Solez K, Colvin RB, Racusen LC et al (2007) Banff ’05 meeting report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (CAN). Am J Transplant 7(3):518–526CrossRefPubMedGoogle Scholar
  52. Spinale HJM, Mariani LH, Kapoor S et al (2015) A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease. Kidney Int 87(3):564–574CrossRefPubMedGoogle Scholar
  53. Surga N, Viart L, Wetzstein M (2013) Impact of renal graft nephrectomy on second transplant survival. Int Urol Nephrol 45(1):87–92CrossRefPubMedGoogle Scholar
  54. Tait BD, Susal C, Gebel HM et al (2013) Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation 15(95):19–47CrossRefGoogle Scholar
  55. Tejani A, Stablein DH (1992) Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. J Am Soc Nephrol 2(12 Suppl):S258–S263PubMedGoogle Scholar
  56. Tittlebach-Helmrich D, Pisarski P, Offermann G et al (2014) Impact of transplant nephrectomy on peak PRA levels and outcome after kidney re-transplantation. World J Transplant 4(2):141–147CrossRefGoogle Scholar
  57. Trachtman R, Sran SS, Trachtman H (2015) Recurrent focal segmental glomerulosclerosis after kidney transplantation. Pediatr Nephrol 30(10):1793–1802CrossRefPubMedGoogle Scholar
  58. Van Amstel SP, Vogelzang J, Starnik M et al (2015) Long-term risk of cancer in survivors of pediatric ESRD. Clin J Am Soc Nephrol 10:1–7CrossRefGoogle Scholar
  59. Vincenti F, Ghiggeri GM (2005) New insights into the pathogenesis and the therapy of recurrent focal glomerulosclerosis. Am J Transplant 5(6):1179–1185CrossRefPubMedGoogle Scholar
  60. Wei C, El Hindi S, Li J, Fornoni A et al (2011) Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 17(8):952–960CrossRefPubMedPubMedCentralGoogle Scholar
  61. Yu CC, Fornoni A, Weins A et al (2013) Abatacept in B7-1 positive proteinuric kidney disease. N Engl J Med 370(13):1263–1266Google Scholar
  62. Zuber J, Le Quintrec M, Krid S et al (2012) Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation. Am J Transplant 12(12):3337–3354CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of NephrologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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