Outcome after Desensitization in HLA or ABO-Incompatible Kidney Transplant Recipients: A Single Center Experience

Teresa Kauke, Sandra Klimaschewski, Ulf Schoenermarck, Michael Fischereder, Andrea Dick, Markus Guba, Manfred Stangl, Jens Werner, Bruno Meiser, Antje Habicht, Teresa Kauke, Sandra Klimaschewski, Ulf Schoenermarck, Michael Fischereder, Andrea Dick, Markus Guba, Manfred Stangl, Jens Werner, Bruno Meiser, Antje Habicht

Abstract

Background: The shortage of deceased donors led to an increase of living donor kidney (LDK) transplantations performed in the presence of donor-specific antibodies (DSA) or ABO incompatibility (ABOi) using various desensitization protocols.

Methods: We herein analyzed 26 ABOi and 8 Luminex positive DSA patients who were successfully desensitized by anti-CD20, antigen-specific immunoadsorption and/or plasmapheresis to receive an LDK transplant. Twenty LDK recipients with non-donor-specific HLA-antibodies (low risk) and 32 without anti-HLA antibodies (no risk) served as control groups.

Results: 1-year graft survival rate and renal function was similar in all 4 groups (creatinine: 1.63 ± 0.5 vs 1.78 ± 0.6 vs 1.64 ± 0.5 vs 1.6 ± 0.3 mg/dl in ABOi, DSA, low risk and no risk group). The incidence of acute T-cell mediated rejections did not differ between the 4 groups (15% vs 12, 5% vs 15% vs 22% in ABOi, DSA, low risk and no risk), while antibody-mediated rejections were only found in the DSA (25%) and ABOi (7.5%) groups. Incidence of BK nephropathy (BKVN) was significantly more frequent after desensitization as compared to controls (5/34 vs 0/52, p = 0.03).

Conclusion: We demonstrate favorable short-term allograft outcome in LDK transplant recipients after desensitization. However, the desensitization was associated with an increased risk of BKVN.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Renal function at 12 month.
Fig 1. Renal function at 12 month.
Renal function, as assessed by serum creatinine levels and estimated GFR (MDRD formula) at 12 months after transplantation.
Fig 2. Loss of renal function within…
Fig 2. Loss of renal function within the first year.
The GFR slope within the first year was assessed according to the following formula: GFR at 1 month−GFR at 12 month.
Fig 3. Incidence of rejection.
Fig 3. Incidence of rejection.
The number of patient experiencing 1 or more biopsy proven rejections (including borderline cases with impaired renal graft function) according to the Banff 97 classification: 2 = antibody mediated rejection (AMR), 3 = borderline lesion, 4 I and 4 II = acute cellular rejection.

References

    1. Smits JM, Van Houwelingen HC, De MJ, Persijn GG, Claas FH Analysis of the renal transplant waiting list: application of a parametric competing risk method. Transplantation 15-November-1998;66:1146–1153.
    1. Picascia A, Infante T, Napoli C: Luminex and antibody detection in kidney transplantation. Clin Exp Nephrol 2012;16:373–381. 10.1007/s10157-012-0635-1
    1. Roelen DL, Doxiadis II, Claas FH: Detection and clinical relevance of donor specific HLA antibodies: a matter of debate. Transpl Int 2012;25:604–610. 10.1111/j.1432-2277.2012.01491.x
    1. Lee PC, Ozawa M, Hung CJ, Lin YJ, Chang SS, Chou TC: Reappraisal of HLA antibody analysis and crossmatching in kidney transplantation. Transplant Proc 2009;41:95–98. 10.1016/j.transproceed.2008.10.074
    1. Patel AM, Pancoska C, Mulgaonkar S, Weng FL: Renal transplantation in patients with pre-transplant donor-specific antibodies and negative flow cytometry crossmatches. Am J Transplant 2007;7:2371–2377.
    1. Bielmann D, Honger G, Lutz D, Mihatsch MJ, Steiger J, Schaub S: Pretransplant risk assessment in renal allograft recipients using virtual crossmatching. Am J Transplant 2007;7:626–632.
    1. Phelan D, Mohanakumar T, Ramachandran S, Jendrisak MD: Living donor renal transplantation in the presence of donor-specific human leukocyte antigen antibody detected by solid-phase assay. Hum Immunol 2009;70:584–588. 10.1016/j.humimm.2009.05.007
    1. van den Berg-Loonen EM, Billen EV, Voorter CE, van Heurn LW, Claas FH, van Hooff JP, Christiaans MH: Clinical relevance of pretransplant donor-directed antibodies detected by single antigen beads in highly sensitized renal transplant patients. Transplantation 27-April-2008;85:1086–1090. 10.1097/TP.0b013e31816b3ed1
    1. Susal C, Ovens J, Mahmoud K, Dohler B, Scherer S, Ruhenstroth A, Tran TH, Heinold A, Opelz G: No association of kidney graft loss with human leukocyte antigen antibodies detected exclusively by sensitive Luminex single-antigen testing: a Collaborative Transplant Study report. Transplantation 27-April-2011;91:883–887. 10.1097/TP.0b013e3182100f77
    1. Susal C, Morath C: Current approaches to the management of highly sensitized kidney transplant patients. Tissue Antigens 2011;77:177–186. 10.1111/j.1399-0039.2011.01638.x
    1. Reinsmoen NL: New approaches for optimizing transplant of sensitized patients. Curr Opin Organ Transplant 2012;17:406–408. 10.1097/MOT.0b013e328355f3c4
    1. Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC: Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 17-July-2008;359:242–251. 10.1056/NEJMoa0707894
    1. Montgomery JR, Berger JC, Warren DS, James NT, Montgomery RA, Segev DL: Outcomes of ABO-incompatible kidney transplantation in the United States. Transplantation 27-March-2012;93:603–609. 10.1097/TP.0b013e318245b2af
    1. Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, Cosio F, David DS, Drachenberg C, Einecke G, Fogo AB, Gibson IW, Glotz D, Iskandar SS, Kraus E, Lerut E, Mannon RB, Mihatsch M, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Roberts I, Seron D, Smith RN, Valente M: Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008;8:753–760. 10.1111/j.1600-6143.2008.02159.x
    1. Mengel M, Sis B, Haas M, Colvin RB, Halloran PF, Racusen LC, Solez K, Cendales L, Demetris AJ, Drachenberg CB, Farver CF, Rodriguez ER, Wallace WD, Glotz D: Banff 2011 Meeting report: new concepts in antibody-mediated rejection. Am J Transplant 2012;12:563–570. 10.1111/j.1600-6143.2011.03926.x
    1. Takahashi K, Saito K: ABO-incompatible kidney transplantation. Transplant Rev (Orlando) 2013;27:1–8.
    1. Klein K, Susal C, Schafer SM, Becker LE, Beimler J, Schwenger V, Zeier M, Schemmer P, her-Goeppinger S, Scherer S, Opelz G, Morath C: Living donor kidney transplantation in patients with donor-specific HLA antibodies enabled by anti-CD20 therapy and peritransplant apheresis. Atheroscler Suppl 2013;14:199–202. 10.1016/j.atherosclerosissup.2012.10.030
    1. Bentall A, Cornell LD, Gloor JM, Park WD, Gandhi MJ, Winters JL, Chedid MF, Dean PG, Stegall MD: Five-year outcomes in living donor kidney transplants with a positive crossmatch. Am J Transplant 2013;13:76–85. 10.1111/j.1600-6143.2012.04291.x
    1. Bagnasco SM, Zachary AA, Racusen LC, Arend LJ, Carter-Monroe N, Alachkar N, Nazarian SM, Lonze BE, Montgomery RA, Kraus ES: Time course of pathologic changes in kidney allografts of positive crossmatch HLA-incompatible transplant recipients. Transplantation 27-February-2014;97:440–445. 10.1097/01.TP.0000437177.40551.f4
    1. Meier-Kriesche HU, Kaplan B: Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation 27-November-2002;74:1377–1381.
    1. Montgomery RA, Lonze BE, King KE, Kraus ES, Kucirka LM, Locke JE, Warren DS, Simpkins CE, Dagher NN, Singer AL, Zachary AA, Segev DL: Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med 28-July-2011;365:318–326. 10.1056/NEJMoa1012376
    1. Hirsch HH, Steiger J: Polyomavirus BK. Lancet Infect Dis 2003;3:611–623.
    1. Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, Mihatsch MJ, Nickeleit V, Ramos E, Randhawa P, Shapiro R, Steiger J, Suthanthiran M, Trofe J: Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 27-May-2005;79:1277–1286.
    1. Hirsch HH: BK virus: opportunity makes a pathogen. Clin Infect Dis 1-August-2005;41:354–360.
    1. Fishman JA: BK virus nephropathy—polyomavirus adding insult to injury. N Engl J Med 15-August-2002;347:527–530.
    1. Mylonakis E, Goes N, Rubin RH, Cosimi AB, Colvin RB, Fishman JA: BK virus in solid organ transplant recipients: an emerging syndrome. Transplantation 27-November-2001;72:1587–1592.
    1. Mengel M, Marwedel M, Radermacher J, Eden G, Schwarz A, Haller H, Kreipe H: Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs. Nephrol Dial Transplant 2003;18:1190–1196.
    1. Binet I, Nickeleit V, Hirsch HH, Prince O, Dalquen P, Gudat F, Mihatsch MJ, Thiel G: Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation 27-March-1999;67:918–922.
    1. Bressollette-Bodin C, Coste-Burel M, Hourmant M, Sebille V, ndre-Garnier E, Imbert-Marcille BM: A prospective longitudinal study of BK virus infection in 104 renal transplant recipients. Am J Transplant 2005;5:1926–1933.
    1. Barbosa D, Kahwaji J, Puliyanda D, Mirocha J, Reinsmoen N, Lai CH, Villicana R, Peng A, Jordan SC, Vo A, Toyoda M: Polyomavirus BK viremia in kidney transplant recipients after desensitization with IVIG and rituximab. Transplantation 15-April-2014;97:755–761. 10.1097/01.TP.0000437671.78716.f3
    1. Habicht A, Broker V, Blume C, Lorenzen J, Schiffer M, Richter N, Klempnauer J, Haller H, Lehner F, Schwarz A: Increase of infectious complications in ABO-incompatible kidney transplant recipients—a single centre experience. Nephrol Dial Transplant 2011;26:4124–4131. 10.1093/ndt/gfr215
    1. Sharif A, Alachkar N, Bagnasco S, Geetha D, Gupta G, Womer K, Arend L, Racusen L, Montgomery R, Kraus E: Incidence and outcomes of BK virus allograft nephropathy among ABO- and HLA-incompatible kidney transplant recipients. Clin J Am Soc Nephrol 2012;7:1320–1327. 10.2215/CJN.00770112

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