Allograft dysfunction is a common problem after kidney transplant. Allograft rejection is an important entity, and timely diagnosis and appropriate treatment are essential for caring transplant recipients. Hyperacute rejection is mediated by the preformed donor specific antibody, while accelerated acute rejection represents an anamnestic response by memory B and T cells. They occur early after transplant. Acute cellular rejection is relatively common and usually responds to pulse corticosteroids or antithymocyte globulin (ATG). The complexity of antibody-mediated rejection (AMR) as well as its detrimental effect has been increasingly recognized. The treatment of acute AMR requires a combination of several modalities, such as plasmapheresis or immunoadsorption, IVIG, corticosteroids, rituximab and ATG. After treatment of rejection episode, the maintenance immunosuppressive drugs should be adjusted to prevent further acute rejection and/or evolution into chronic active rejection. Chronic rejection is not reversible and it has been recognized as the most important cause of chronic graft dysfunction and failure.
References
[1]
Zhang, R., Kumar, P., Ramcharan, T. and Reisin, E. (2004) Kidney Transplantation: The Evolving Challenges. The American Journal of the Medical Sciences, 328, 156-161.
http://dx.doi.org/10.1097/00000441-200409000-00004
[2]
Kumbala, D. and Zhang, R. (2013) The Essential Concept of Transplant Immunology for Clinical Practice. World Journal of Transplantation, 3, 113-118.
[3]
Djamali, A., Kaufman, D.B., Ellis, T.M., Zhong, W., Matas, A. and Samaniego, A. (2014) Diagnosis and Mamagement of Antibody-Mediated Rejection: Current Status and Novel Approaches. American Journal of Transplantation, 14, 255-271.
http://dx.doi.org/10.1111/ajt.12589
[4]
Solez, K., Colvin, R.B., Racusen, L.C., Haas, M., Sis, B., Mengel, M., Halloran, P.F., Baldwin, W., Banfi, G., Collins, A.B., Cosio, F., David, D.S., Drachenberg, C., Einecke, G., Fogo, A.B., Gibson, I.W., Glotz, D., Iskandar, S.S., Kraus, E., Lerut, E., Mannon, R.B., Mihatsch, M., Nankivell, B.J., Nickeleit, V., Papadimitriou, J.C., Randhawa, P., Regele, H., Renaudin, K., Roberts, I., Seron, D., Smith, R.N. and Valente, M. (2008) Banff 07 Classification of Renal Allograft Pathology: Updates and Future Directions. American Journal of Transplantation, 8, 753-760.
http://dx.doi.org/10.1111/j.1600-6143.2008.02159.x
[5]
Haas, M., Sis, B., Racusen, L.C., Solez, K., Glotz, D., Colvin, R.B., Castro, M.C., David, D.S., David-Neto, E., Bagnasco, S.M., Cendales, L.C., Cornell, L.D., Demetris, A.J., Drachenberg, C.B., Farver, C.F., Farris 3rd, A.B., Gibson, I.W., Kraus, E., Liapis, H., Loupy, A., Nickeleit, V., Randhawa, P., Rodriguez, E.R., Rush, D., Smith, R.N., Tan, C.D., Wallace, W.D., Mengel, M. and Banff Meeting Report Writing Committee (2014) Banff 2013 Meeting Report: Inclusion of c4d-Negative Antibody-Mediated Rejection and Antibody-Associated Arterial Lesions. American Journal of Transplantation, 14, 272-283.
http://dx.doi.org/10.1111/ajt.12590
[6]
Saidi, R.F., Elias, N., Kawai, T., Hertl, M., Farrell, M.L. and Goes, N. (2007) Outcome of Kidney Transplantation Using Expanded Criteria Donors and Donation after Cardiac Death Kidneys: Realities and Costs. American Journal of Transplantation, 7, 2769-2774.
http://dx.doi.org/10.1111/j.1600-6143.2007.01993.x
[7]
Humar, A. and Matas, A.J. (2005) Surgical Complications after Kidney Transplantation. Seminars in Dialysis, 18, 505- 510.
http://dx.doi.org/10.1111/j.1525-139X.2005.00097.x
[8]
Shinn, C., Malhotra, D., Chan, L., Cosby, R.L. and Shapiro, J.I. (1999) Time Course of Response to Pulse Methylprednisolone Therapy in Renal Transplant Recipients with Acute Allograft Rejection. American Journal of Kidney Diseases, 34, 304-307.
http://dx.doi.org/10.1016/S0272-6386(99)70359-8
[9]
Gray, D., Shepherd, H., Daar, A., Oliver, D.O. and Morris, P.J. (1978) Oral versus Intravenous High-Dose Steroid Treatment of Renal Allograft Rejection. The Big Shot or Not? Lancet, 1, 117-118.
http://dx.doi.org/10.1016/S0140-6736(78)90417-8
[10]
Gaber, A.O., First, M.R., Tesi, R.J., Gaston, R.S., Mendez, R., Mulloy, L.L., et al. (1998) 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, 66, 29-37.
http://dx.doi.org/10.1097/00007890-199807150-00005
[11]
Webster, A.C., Pankhurst, T., Rinaldi, F., Chapman, J.R. and Craig, J.C. (2006) Monoclonal and Polyclonal Antibody Therapy for Treating Acute Rejection in Kidney Transplant Recipients: A Systematic Review of Randomized Trial Data. Transplantation, 81, 953-965.
http://dx.doi.org/10.1097/01.tp.0000215178.72344.9d
[12]
Worthington, J.E., McEwen, A., McWilliam, L.J., Picton, M.L. and Martin, S. (2007) Association between C4d Staining in Renal Transplant Biopsies, Production of Donor-Specific HLA Antibodies, and Graft Outcome. Transplantation, 83, 398-403.
http://dx.doi.org/10.1097/01.tp.0000251430.11723.b6
[13]
Mengel, M., Sis, B., Haas, M., Colvin, R.B., Halloran, P.F., Racusen, L.C., et al. (2012) Banff 2011 Meeting Report: New Concepts in Antibody-Mediated Rejection. American Journal of Transplantation, 12, 563-570.
http://dx.doi.org/10.1111/j.1600-6143.2011.03926.x
[14]
Montgomery, R.A., Hardy, M.A., Jordan, S.C., Racusen, L.C., Ratner, L.E., Tyan, D.B. and Zachary, A.A. (2004) Consensus Opinion from the Antibody Working Group on the Diagnosis, Reporting, and Risk Assessment for Antibody-Mediated Rejection and Desensitization Protocols. Transplantation, 78, 181-185.
http://dx.doi.org/10.1097/01.TP.0000129256.84027.D6
[15]
Hidalgo, L.G., Campbell, P.M., Sis, B., Einecke, G., Mengel, M., Chang, J., Sellares, J., Reeve, J. and Halloran, P.F. (2009) De Novo Donor-Specific Antibody at the Time of Kidney Transplant Biopsy Associates with Microvascular Pathology and Late Graft Failure. American Journal of Transplantation, 9, 2532-2541.
http://dx.doi.org/10.1111/j.1600-6143.2009.02800.x
[16]
Troxell, M.L., Weintraub, L.A., Higgins, J.P. and Kambham, N. (2006) Comparison of C4d Immunostaining Methods in Renal Allograft Biopsies. Clinical Journal of the American Society of Nephrology, 1, 583-591.
http://dx.doi.org/10.2215/CJN.00900805
[17]
Hankey, K.G., Drachenberg, C.B., Papadimitriou, J.C., Klassen, D.K., Philosophe, B., Bartlett, S.T., Groh, V., Spies, T. and Mann, D.L. (2002) MIC Expression in Renal and Pancreatic Allografts. Transplantation, 73, 304-306.
http://dx.doi.org/10.1097/00007890-200201270-00029
[18]
Sun, Q., Cheng, Z., Cheng, D., Chen, J., Ji, S., Wen, J., et al. (2011) De Novo Development of Circulating Anti-Endothelial Cell Antibodies rather than Pre-Existing Antibodies Is Associated with Post-Transplant Allograft Rejection. Kidney International, 79, 655-662.
http://dx.doi.org/10.1038/ki.2010.437
[19]
Rocha, P.N., Butterly, D.W., Greenberg, A., Reddan, D.N., Tuttle-Newhall, J., Collins, B.H., et al. (2003) Beneficial Effect of Plasmapheresis and Intravenous Immunoglobulin on Renal Allograft Survival of Patients with Acute Humoral Rejection. Transplantation, 75, 1490-1495.
http://dx.doi.org/10.1097/01.TP.0000060252.57111.AC
[20]
Mulley, W.R., Hudson, F.J., Tait, B.D., Skene, A.M., Dowling, J.P., Kerr, P.G., et al. (2009) A Single Low-Fixed Dose of Rituximab to Salvage Renal Transplants from Refractory Antibody-Mediated Rejection. Transplantation, 87, 286- 289.
http://dx.doi.org/10.1097/TP.0b013e31819389cc
[21]
Zhang, R. (2013) Modern Immunosuppressive Therapy in Kidney Transplantation. Open Journal of Organ Transplant Surgery, 3, 22-31.
http://dx.doi.org/10.4236/ojots.2013.32005
[22]
Everly, M.J., Everly, J.J., Susskind, B., Brailey, P., Arend, L.J., Alloway, R.R., et al. (2008) Bortezomib Provides Effective Therapy for Antibody- and Cell-Mediated Acute Rejection. Transplantation, 86, 1754-1761.
http://dx.doi.org/10.1097/TP.0b013e318190af83
[23]
Locke, J.E., Zachary, A.A., Haas, M., Melancon, J.K., Warren, D.S., Simpkins, C.E., et al. (2007) The Utility of Splenectomy as Rescue Treatment for Severe Acute Antibody Mediated Rejection. American Journal of Transplantation, 7, 842-846.
http://dx.doi.org/10.1111/j.1600-6143.2006.01709.x
[24]
Lorenz, M., Regele, H., Schillinger, M., Kletzmayr, J., Haidbauer, B., Derfler, K., et al. (2005) Peritransplantimmunoadsorption: A Strategy Enabling Transplantation in Highly Sensitized Crossmatch-Positive Cadaveric Kidney Allograft Recipients. Transplantation, 79, 696-701.
http://dx.doi.org/10.1097/01.TP.0000148732.26761.FA
[25]
Luke, P.P., Scantlebury, V.P., Jordan, M.L., Vivas, C.A., Hakala, T.R., Jain, A., et al. (2001) Reversal of Steroid- and Anti-Lymphocyte Antibody-Resistant Rejection Using Intravenous Immunoglobulin (IVIG) in Renal Transplant Recipients. Transplantation, 72, 419-422.
http://dx.doi.org/10.1097/00007890-200108150-00010
[26]
Locke, J.E., Magro, C.M., Singer, A.L., Segev, D.L., Haas, M., Hillel, A.T., et al. (2009) The Use of Antibody to Complement Protein C5 for Salvage Treatment of Severe Antibody-Mediated Rejection. American Journal of Transplantation, 9, 231-235.
http://dx.doi.org/10.1111/j.1600-6143.2008.02451.x
[27]
Opelz, G. and Dohler, B., Collaborative Transplant Study Report (2008) Influence of Time of Rejection on Long-Term Graft Survival in Renal Transplantation. Transplantation, 85, 661-666.
http://dx.doi.org/10.1097/TP.0b013e3181661695
[28]
Madden, R.L., Mulhern, J.G., Benedetto, B.J., O’Shea, M.H., Germain, M.J., Braden, G.L., et al. (2000) Completely Reversed Acute Rejection Is Not a Significant Risk Factor for the Development of Chronic Rejection in Renal Allograft Recipients. Transplant International, 13, 344-350.
http://dx.doi.org/10.1111/j.1432-2277.2000.tb01008.x
[29]
Woodle, E.S., Thistlethwaite, J.R., Gordon, J.H., Laskow, D., Deierhoi, M.H., Burdick, J., et al. (1996) A Multicenter Trial of FK506 (Tacrolimus) Therapy in Refractory Acute Renal Allograft Rejection: A Report of the Tacrolimus Kidney Transplantation Rescue Study Group. Transplantation, 62, 594-599.
http://dx.doi.org/10.1097/00007890-199609150-00009
[30]
Briggs, D., Dudley, C., Pattison, J., Pfeffer, P., Salmela, K., Rowe, P., et al. (2003) Effects of Immediate Switch from Cyclosporine Microemulsion to Tacrolimus at First Acute Rejection in Renal Allograft Recipients. Transplantation, 75, 2058-2063.
http://dx.doi.org/10.1097/01.TP.0000069041.48226.DD
[31]
Clatworthy, M.R., Friend, P.J., Calne, R.Y., Rebello, P.R., Hale, G., Waldmann, H., et al. (2009) Alemtuzumab (CAMPATH-1H) for the Treatment of Acute Rejection in Kidney Transplant Recipients: Long-Term Follow-Up. Transplantation, 87, 1092-1095.
http://dx.doi.org/10.1097/TP.0b013e31819d3353
[32]
Csapo, Z., Benavides-Viveros, C., Podder, H., Pollard, V. and Kahan, B.D. (2005) Campath-1H as Rescue Therapy for the Treatment of Acute Rejection in Kidney Transplant Patients. Transplantation Proceedings, 37, 2032-2036.
http://dx.doi.org/10.1016/j.transproceed.2005.03.042
[33]
Wahl, A.O., Small Jr., W., Dixler, I., Strom, S., Rademaker, A., Leventhal, J., et al. (2006) Radiotherapy for Rejection of Renal Transplant Allografts Refractory to Medical Immunosuppression. American Journal of Clinical Oncology, 29, 551-554.
http://dx.doi.org/10.1097/01.coc.0000231452.47998.88
[34]
Rush, D., Arlen, D., Boucher, A., Busque, S., Cockfield, S.M., Girardin, C., et al. (2007) Lack of Benefit of Early Protocol Biopsies in Renal Transplant Patients Receiving TAC and MMF: A Randomized Study. American Journal of Transplantation, 7, 2538-2545.
http://dx.doi.org/10.1111/j.1600-6143.2007.01979.x
[35]
Seron, D. and Moreso, F. (2007) Protocol Biopsies in Renal Transplantation: Prognostic Value of Structural Monitoring. Kidney International, 72, 690-697.
http://dx.doi.org/10.1038/sj.ki.5002396
[36]
Nemeth, D., Ovens, J., Opelz, G., Sommerer, C., Dohler, B., Becker, L.E., et al. (2010) Does Borderline Kidney Allograft Rejection Always Require Treatment? Transplantation, 90, 427-432.
http://dx.doi.org/10.1097/TP.0b013e3181e81b16
[37]
Fehr, T. and Gaspert, A. (2012) Antibody-Mediated Kidney Allograft Rejection: Therapeutic Options and Their Experimental Rationale. Transplant International, 25, 623-632.
[38]
Smith, R.N., Malik, F., Goes, N., et al. (2012) Partial Therapeutic Response to Rituximab for the Treatment of Chronic Alloantibody Mediated Rejection of Kidney Allografts. Transplant Immunology, 27, 107-113.
http://dx.doi.org/10.1016/j.trim.2012.08.005
[39]
Li, B., Hartono, C., Ding, R., Sharma, V.K., Ramaswamy, R., Qian, B., Serur, D., Mouradian, J., Schwartz, J.E. and Suthanthiran, M. (2001) Noninvasive Diagnosis of Renal-Allograft Rejection by Measurement of Messenger RNA for Perforin and Granzyme B in Urine. The New England Journal of Medicine, 344, 947-954.
http://dx.doi.org/10.1056/NEJM200103293441301
[40]
O'Riordan, E., Orlova, T.N., Mei, J.J., Butt, K., Chander, P.M., Rahman, S., Mya, M., Hu, R., Momin, J., Eng, E.W., Hampel, D.J., Hartman, B., Kretzler, M., Delaney, V. and Goligorsky, M.S. (2004) Bioinformatic Analysis of the Urine Proteome of Acute Allograft Rejection. Journal of the American Society of Nephrology, 15, 3240-3248.
http://dx.doi.org/10.1097/01.ASN.0000145241.83482.68
[41]
Renesto, P.G., Ponciano, V.C., Cenedeze, M.A., et al. (2007) High Expression of Tim-3 mRNA in Urinary Cells from Kidney Transplant Recipients with Acute Rejection. American Journal of Transplantation, 7, 1661-1666.
http://dx.doi.org/10.1111/j.1600-6143.2007.01795.x
[42]
Metzger, J., Chatzikyrkou, C., Broecker, V., Schiffer, E., Jaensch, L., Iphoefer, A., Mengel, M., Mullen, W., Mischak, H., Haller, H. and Gwinner, W. (2011) Diagnosis of Subclinical and Clinical Acute T-Cell-Mediated Rejection in Renal Transplant Patients by Urinary Proteome Analysis. Proteomics-Clinical Applications, 5, 322-333.
http://dx.doi.org/10.1002/prca.201000153
[43]
Heidt, S., San Segundo, D., Shankar, S., et al. (2011) Peripheral Blood Sampling for the Detection of Allograft Rejection: Biomarker Identification and Validation. Transplantation, 92, 1-9.
[44]
Flechner, S.M., Kurian, S.M., Head, S.R., et al. (2004) Kidney Transplant Rejection and Tissue Injury by Gene Profiling of Biopsies and Peripheral Blood Lymphocytes. American Journal of Transplantation, 4, 1475-1479.
[45]
Bestard, O., Cruzado, J.M., Franquesa, M.L. and Grinyo, J.M. (2010) Biomarkers in Renal Transplantation. Current Opinion in Organ Transplantation, 15, 467-473.
[46]
Suthanthiran, M., Schwartz, J.E., Ding, R., et al. (2013) Urinary-Cell mRNA and Acute Cellular Rejection in Kidney Allografts. The New England Journal of Medicine, 369, 20-31.
http://dx.doi.org/10.1097/TP.0b013e318218e978
