Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Treatment of acute T cell-mediated (cellular) rejection of the renal allograft

Daniel C Brennan, MD, FACP
Andrew Malone, MB, BCh, MRCPI
Section Editor
Barbara Murphy, MB, BAO, BCh, FRCPI
Deputy Editor
Albert Q Lam, MD


The use of potent immunosuppressive agents as part of induction and maintenance therapy for renal transplantation has significantly reduced the incidence of acute rejection, which is defined as an acute deterioration in kidney allograft function associated with specific pathologic changes in the graft. With existing immunosuppressive protocols, acute rejection rates have fallen to approximately 8 percent at most transplant centers [1].

Acute rejection can be broadly categorized into T cell-mediated (cellular) rejection (TCMR) and antibody-mediated (previously known as humoral) rejection (ABMR). A renal allograft biopsy is required to establish the diagnosis and determine the severity of rejection in order to determine the appropriate approach to therapy. TCMR and ABMR may also coexist at the same time in the renal allograft (ie, mixed acute rejection). The presence of histologic evidence of acute rejection on biopsy without an elevation in the serum creatinine concentration is known as subclinical rejection.

The treatment of acute TCMR of the renal allograft will be reviewed here. The clinical features and diagnosis of acute rejection and the treatment of acute ABMR are discussed separately. (See "Clinical features and diagnosis of acute renal allograft rejection" and "Prevention and treatment of antibody-mediated rejection of the renal allograft".)


Acute TCMR occurs most commonly within the first year after transplantation and rarely occurs after five years posttransplant [2,3]. In general, episodes of acute rejection have been associated with a reduction in long-term allograft survival, although not all rejection episodes have the same impact on long-term graft function. (See "Clinical features and diagnosis of acute renal allograft rejection", section on 'Epidemiology and outcomes' and "Risk factors for graft failure in kidney transplantation", section on 'Episodes of acute rejection'.)

The impact of successfully treating acute TCMR on graft outcomes has not been well studied. Greater histologic severity of acute TCMR (ie, Banff grade greater than IA) has been associated with lower response rates to therapy [4]. Higher histologic scores (eg, i: interstitial inflammation, t: tubulitis, v: intimal arteritis) and a later onset of rejection (>3 months posttransplant) have been associated with worse graft outcomes [5,6]. (See "Clinical features and diagnosis of acute renal allograft rejection", section on 'Acute T cell-mediated (cellular) rejection'.)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Oct 2017. | This topic last updated: Oct 03, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2015 Annual Data Report: Kidney. Am J Transplant 2017; 17 Suppl 1:21.
  2. Halloran PF, Pereira AB, Chang J, et al. Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: The INTERCOM study. Am J Transplant 2013; 13:2352.
  3. Sellarés J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 2012; 12:388.
  4. Lamarche C, Côté JM, Sénécal L, Cardinal H. Efficacy of Acute Cellular Rejection Treatment According to Banff Score in Kidney Transplant Recipients: A Systematic Review. Transplant Direct 2016; 2:e115.
  5. Naesens M, Kuypers DR, De Vusser K, et al. The histology of kidney transplant failure: a long-term follow-up study. Transplantation 2014; 98:427.
  6. Wu K, Budde K, Schmidt D, et al. The Relationship of the Severity and Category of Acute Rejection With Intimal Arteritis Defined in Banff Classification to Clinical Outcomes. Transplantation 2015; 99:e105.
  7. Modena BD, Kurian SM, Gaber LW, et al. Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes. Am J Transplant 2016; 16:1982.
  8. Park WD, Griffin MD, Cornell LD, et al. Fibrosis with inflammation at one year predicts transplant functional decline. J Am Soc Nephrol 2010; 21:1987.
  9. Naesens M, Kuypers DR, De Vusser K, et al. Chronic histological damage in early indication biopsies is an independent risk factor for late renal allograft failure. Am J Transplant 2013; 13:86.
  10. Gray D, Shepherd H, Daar A, et al. Oral versus intravenous high-dose steroid treatment of renal allograft rejection. The big shot or not? Lancet 1978; 1:117.
  11. Vineyard GC, Fadem SZ, Dmochowski J, et al. Evaluation of corticosteroid therapy for acute renal allograft rejection. Surg Gynecol Obstet 1974; 138:225.
  12. Boothpur R, Hardinger KL, Skelton RM, et al. Serum sickness after treatment with rabbit antithymocyte globulin in kidney transplant recipients with previous rabbit exposure. Am J Kidney Dis 2010; 55:141.
  13. Zand MS, Vo T, Huggins J, et al. Polyclonal rabbit antithymocyte globulin triggers B-cell and plasma cell apoptosis by multiple pathways. Transplantation 2005; 79:1507.
  14. Filo RS, Smith EJ, Leapman SB. Therapy of acute cadaveric renal allograft rejection with adjunctive antithymocyte globulin. Transplantation 1980; 30:445.
  15. Hoitsma AJ, Reekers P, Kreeftenberg JG, et al. Treatment of acute rejection of cadaveric renal allografts with rabbit antithymocyte globulin. Transplantation 1982; 33:12.
  16. Hoitsma AJ, van Lier HJ, Reekers P, Koene RA. Improved patient and graft survival after treatment of acute rejections of cadaveric renal allografts with rabbit antithymocyte globulin. Transplantation 1985; 39:274.
  17. Streem SB, Novick AC, Braun WE, et al. Low-dose maintenance prednisone and antilymphoblast globulin for the treatment of acute rejection. A steroid-sparing approach to immunosuppressive therapy. Transplantation 1983; 35:420.
  18. Gaber AO, First MR, Tesi RJ, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation 1998; 66:29.
  19. Agha IA, Rueda J, Alvarez A, et al. Short course induction immunosuppression with thymoglobulin for renal transplant recipients. Transplantation 2002; 73:473.
  20. Hardinger KL, Rasu RS, Skelton R, et al. Thymoglobulin induction dosing strategies in a low-risk kidney transplant population: three or four days? J Transplant 2010; 2010:957549.
  21. Burton SA, Amir N, Asbury A, et al. Treatment of antibody-mediated rejection in renal transplant patients: a clinical practice survey. Clin Transplant 2015; 29:118.
  22. Friend PJ, Rebello P, Oliveira D, et al. Successful treatment of renal allograft rejection with a humanized antilymphocyte monoclonal antibody. Transplant Proc 1995; 27:869.
  23. Basu A, Ramkumar M, Tan HP, et al. Reversal of acute cellular rejection after renal transplantation with Campath-1H. Transplant Proc 2005; 37:923.
  24. Csapo Z, Benavides-Viveros C, Podder H, et al. Campath-1H as rescue therapy for the treatment of acute rejection in kidney transplant patients. Transplant Proc 2005; 37:2032.
  25. Upadhyay K, Midgley L, Moudgil A. Safety and efficacy of alemtuzumab in the treatment of late acute renal allograft rejection. Pediatr Transplant 2012; 16:286.
  26. Németh D, Ovens J, Opelz G, et al. Does borderline kidney allograft rejection always require treatment? Transplantation 2010; 90:427.
  27. Bestard O, Cruzado JM, Rama I, et al. Presence of FoxP3+ regulatory T Cells predicts outcome of subclinical rejection of renal allografts. J Am Soc Nephrol 2008; 19:2020.
  28. Rush DN, Henry SF, Jeffery JR, et al. Histological findings in early routine biopsies of stable renal allograft recipients. Transplantation 1994; 57:208.
  29. Shapiro R, Jordan ML, Scantlebury VP, et al. Renal allograft rejection with normal renal function in simultaneous kidney/pancreas recipients: does dissynchronous rejection really exist? Transplantation 2000; 69:440.
  30. Roberts IS, Reddy S, Russell C, et al. Subclinical rejection and borderline changes in early protocol biopsy specimens after renal transplantation. Transplantation 2004; 77:1194.
  31. Kee TY, Chapman JR, O'Connell PJ, et al. Treatment of subclinical rejection diagnosed by protocol biopsy of kidney transplants. Transplantation 2006; 82:36.
  32. Nankivell BJ, Chapman JR. The significance of subclinical rejection and the value of protocol biopsies. Am J Transplant 2006; 6:2006.
  33. Scholten EM, Rowshani AT, Cremers S, et al. Untreated rejection in 6-month protocol biopsies is not associated with fibrosis in serial biopsies or with loss of graft function. J Am Soc Nephrol 2006; 17:2622.
  34. Serón D, Moreso F. Protocol biopsies in renal transplantation: prognostic value of structural monitoring. Kidney Int 2007; 72:690.
  35. Thaunat O, Legendre C, Morelon E, et al. To biopsy or not to biopsy? Should we screen the histology of stable renal grafts? Transplantation 2007; 84:671.
  36. Rush D, Arlen D, Boucher A, et al. Lack of benefit of early protocol biopsies in renal transplant patients receiving TAC and MMF: a randomized study. Am J Transplant 2007; 7:2538.
  37. Rush D, Nickerson P, Gough J, et al. Beneficial effects of treatment of early subclinical rejection: a randomized study. J Am Soc Nephrol 1998; 9:2129.
  38. Kurtkoti J, Sakhuja V, Sud K, et al. The utility of 1- and 3-month protocol biopsies on renal allograft function: a randomized controlled study. Am J Transplant 2008; 8:317.
  39. Kasiske BL, Vazquez MA, Harmon WE, et al. Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation. J Am Soc Nephrol 2000; 11 Suppl 15:S1.
  40. Sis B, Bagnasco SM, Cornell LD, et al. Isolated endarteritis and kidney transplant survival: a multicenter collaborative study. J Am Soc Nephrol 2015; 26:1216.
  41. Wu K, Budde K, Lu H, et al. The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes. Transplantation 2014; 97:1146.
  42. Woodle ES, Cronin D, Newell KA, et al. Tacrolimus therapy for refractory acute renal allograft rejection: definition of the histologic response by protocol biopsies. Transplantation 1996; 62:906.
  43. Pichette V, Bonnardeaux A, Prudhomme L, et al. Long-term bone loss in kidney transplant recipients: a cross-sectional and longitudinal study. Am J Kidney Dis 1996; 28:105.
  44. Marvin MR, Droogan C, Sawinski D, et al. Administration of rabbit antithymocyte globulin (thymoglobulin) in ambulatory renal-transplant patients. Transplantation 2003; 75:488.
  45. Deeks ED, Keating GM. Rabbit antithymocyte globulin (thymoglobulin): a review of its use in the prevention and treatment of acute renal allograft rejection. Drugs 2009; 69:1483.
  46. Christiaans MH, van Hooff JP. Plasmapheresis and RATG-induced serum sickness. Transplantation 2006; 81:296.
  47. Tanriover B, Chuang P, Fishbach B, et al. Polyclonal antibody-induced serum sickness in renal transplant recipients: treatment with therapeutic plasma exchange. Transplantation 2005; 80:279.
  48. Pham PT, Pham PM, Miller JM, Pham PC. Polyclonal antibody-induced serum sickness presenting as rapidly progressive descending paralysis. Transplantation 2007; 83:1657.