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Review

Impact of low tacrolimus exposure and high tacrolimus intra-patient variability on the development of de novo anti-HLA donor-specific antibodies in kidney transplant recipients

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Pages 1323-1331 | Received 30 Jul 2019, Accepted 12 Nov 2019, Published online: 27 Nov 2019

References

  • Nankivell BJ, Kuypers DR. Diagnosis and prevention of chronic kidney allograft loss. Lancet. 2011 Oct 15;378(9800):1428–1437. PubMed PMID: 22000139.
  • Loupy A, Hill GS, Jordan SC. The impact of donor-specific anti-HLA antibodies on late kidney allograft failure. Nat Rev Nephrol. 2012 Apr 17;8(6):348–357. PubMed PMID: 22508180.
  • Ojo AO, Morales JM, González-Molina M, et al. Comparison of the long-term outcomes of kidney transplantation: USA versus Spain. Nephrol Dialysis Transplantation. 2012;28(1):213–220.
  • Coemans M, Süsal C, Döhler B, et al. Analyses of the short- and long-term graft survival after kidney transplantation in Europe between 1986 and 2015. Kidney Int. 2018;94:964–973.
  • Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant. 2004 Aug;4(8):1289–1295. PubMed PMID: 15268730.
  • Neuberger JM, Bechstein WO, Kuypers DR, et al. Practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients: a Guidance report and clinical checklist by the Consensus On Managing Modifiable Risk In Transplantation (COMMIT) Group. Transplantation. 2017 Apr;101(4S Suppl 2):S1–S56. PubMed PMID: 28328734.
  • Djamali A, Kaufman DB, Ellis TM, et al. Diagnosis and management of antibody-mediated rejection: current status and novel approaches. Am J Transplant. 2014 Feb;14(2):255–271. PubMed PMID: 24401076.
  • Vo AA, Sinha A, Haas M, et al. Factors predicting risk for antibody-mediated rejection and graft loss in highly human leukocyte antigen sensitized patients transplanted after desensitization. Transplantation. 2015 Jul;99(7):1423–1430. PubMed PMID: 25606792.
  • Loupy A, Lefaucheur C. Antibody-mediated rejection of solid-organ allografts. N Engl J Med. 2018 Sep 20;379(12):1150–1160. PubMed PMID: 30231232.
  • Sellares 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 Feb;12(2):388–399. PubMed PMID: 22081892.
  • Loupy A, Suberbielle-Boissel C, Hill GS, et al. Outcome of subclinical antibody-mediated rejection in kidney transplant recipients with preformed donor-specific antibodies. Am J Transplant. 2009 Nov;9(11):2561–2570. PubMed PMID: 19775320.
  • Jordan SC, Vo AA. Donor-specific antibodies in allograft recipients: etiology, impact and therapeutic approaches. Curr Opin Organ Transplant. 2014 Dec;19(6):591–597. PubMed PMID: 25304815.
  • Butler CL, Valenzuela NM, Thomas KA, et al. Not all antibodies are created equal: factors that influence antibody mediated rejection. J Immunol Res. 2017;2017:7903471. PubMed PMID: 28373996.
  • Aubert O, Loupy A, Hidalgo L, et al. Antibody-mediated rejection due to preexisting versus De Novo donor-specific antibodies in kidney allograft recipients. J Am Soc Nephrol. 2017 Jun;28(6):1912–1923. PubMed PMID: 28255002.
  • Amico P, Honger G, Mayr M, et al. Clinical relevance of pretransplant donor-specific HLA antibodies detected by single-antigen flow-beads. Transplantation. 2009 Jun 15;87(11):1681–1688. PubMed PMID: 19502960.
  • Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody. Am J Transplant. 2015 Nov;15(11):2921–2930. PubMed PMID: 26096305.
  • Lionaki S, Panagiotellis K, Iniotaki A, et al. Incidence and clinical significance of de novo donor specific antibodies after kidney transplantation. Clin Dev Immunol. 2013;2013:849835. PubMed PMID: 24348683.
  • Monfa E, San Segundo D, San Millan JCR, et al. Intermediate steroid withdrawal after renal transplantation and anti-HLA antibodies (HLA-Abs) development. Nefrologia. 2017 Jul - Aug;37(4):415–422. PubMed PMID: 28330741.
  • Kidney Disease: improving Global Outcomes Transplant Work G. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9(Suppl 3):S1–155. PubMed PMID: 19845597.
  • Hesselink DA, Bouamar R, Elens L, et al. The role of pharmacogenetics in the disposition of and response to tacrolimus in solid organ transplantation. Clin Pharmacokinet. 2014 Feb;53(2):123–139. PubMed PMID: 24249597.
  • Andrews LM, Li Y, De Winter BCM, et al. Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients. Expert Opin Drug Metab Toxicol. 2017 Dec;13(12):1225–1236. PubMed PMID: 29084469.
  • Brunet M, van Gelder T, Asberg A, et al. Therapeutic drug monitoring of tacrolimus-personalized therapy: second consensus report. Ther Drug Monit. 2019 Jun;41(3):261–307. PubMed PMID: 31045868.
  • Shuker N, van Gelder T, Hesselink DA. Intra-patient variability in tacrolimus exposure: causes, consequences for clinical management. Transplantation Rev. 2015 Apr;29(2):78–84. PubMed PMID: 25687818.
  • Gijsen VM, Madadi P, Dube MP, et al. Tacrolimus-induced nephrotoxicity and genetic variability: a review. Ann Transplant. 2012 Apr-Jun;17(2):111–121. PubMed PMID: 22743729.
  • Seibert SR, Schladt DP, Wu B, et al. Tacrolimus trough and dose intra-patient variability and CYP3A5 genotype: effects on acute rejection and graft failure in European American and African American kidney transplant recipients. Clin Transplant. 2018 Dec;32(12):e13424. PubMed PMID: 30318646.
  • Whalen HR, Glen JA, Harkins V, et al. High intrapatient tacrolimus variability is associated with worse outcomes in renal transplantation using a low-dose tacrolimus immunosuppressive regime. Transplantation. 2017 Feb;101(2):430–436. PubMed PMID: 26950724.
  • Leino AD, King EC, Jiang W, et al. Assessment of tacrolimus intrapatient variability in stable adherent transplant recipients: establishing baseline values. Am J Transplant. 2018 Dec 1;19(5):1410-1420. PubMed PMID: 30506623.
  • Borra LC, Roodnat JI, Kal JA, et al. High within-patient variability in the clearance of tacrolimus is a risk factor for poor long-term outcome after kidney transplantation. Nephrol Dial Transplant. 2010 Aug;25(8):2757–2763. PubMed PMID: 20190242.
  • Sapir-Pichhadze R, Wang Y, Famure O, et al. Time-dependent variability in tacrolimus trough blood levels is a risk factor for late kidney transplant failure. Kidney Int. 2014 Jun;85(6):1404–1411. PubMed PMID: 24336032.
  • Shuker N, Shuker L, van Rosmalen J, et al. A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation. Transpl Int. 2016 Nov;29(11):1158–1167. PubMed PMID: 27188932.
  • van Gelder T. Within-patient variability in immunosuppressive drug exposure as a predictor for poor outcome after transplantation. Kidney Int. 2014 Jun;85(6):1267–1268. PubMed PMID: 24875549.
  • O’Regan JA, Canney M, Connaughton DM, et al. Tacrolimus trough-level variability predicts long-term allograft survival following kidney transplantation [journal article]. J Nephrol. 2016 April 01;29(2):269–276.
  • Süsal C, Döhler B. Late intra-patient tacrolimus trough level variability as a major problem in kidney transplantation: a collaborative transplant study report. Am J Transplant. 2019;19(10):2805–2813.
  • Sablik KA, Clahsen-van Groningen MC, Hesselink DA, et al. Tacrolimus intra-patient variability is not associated with chronic active antibody mediated rejection. PLoS One. 2018;13(5):e0196552. PubMed PMID: 29746495.
  • Stebegg M, Kumar SD, Silva-Cayetano A, et al. Regulation of the Germinal Center Response. Front Immunol. 2018;9:2469. PubMed PMID: 30410492.
  • Mesin L, Ersching J, Victora GD. Germinal center B cell dynamics. Immunity. 2016 Sep 20;45(3):471–482. PubMed PMID: 27653600.
  • Yan L, de Leur K, Hendriks RW, et al. T follicular helper cells as a new target for immunosuppressive therapies. Front Immunol. 2017;8:1510. PubMed PMID: 29163552.
  • Baan CC, de Graav GN, Boer K. T follicular helper cells in transplantation: the target to attenuate antibody-mediated allogeneic responses? Curr Transplant Rep. 2014;1(3):166–172. PubMed PMID: 25927019.
  • Weinstein JS, Bertino SA, Hernandez SG, et al. B cells in T follicular helper cell development and function: separable roles in delivery of ICOS ligand and antigen. J Immunol. 2014 Apr 1;192(7):3166–3179. PubMed PMID: 24610013.
  • Ionescu L, Urschel S. Memory B-cells and long-lived plasma cells. Transplantation. 2019 Feb 4;103:890–898. PubMed PMID: 30747835.
  • de Leur K, Dor FJ, Dieterich M, et al. IL-21 receptor antagonist inhibits differentiation of B cells toward plasmablasts upon alloantigen stimulation. Front Immunol. 2017;8:306. PubMed PMID: 28373876.
  • Chung Y, Tanaka S, Chu F, et al. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med. 2011 Jul 24;17(8):983–988. PubMed PMID: 21785430.
  • Wollenberg I, Agua-Doce A, Hernandez A, et al. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J Immunol. 2011 Nov 1;187(9):4553–4560. PubMed PMID: 21984700.
  • Linterman MA, Pierson W, Lee SK, et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med. 2011 Jul 24;17(8):975–982. PubMed PMID: 21785433.
  • Wallin EF. T follicular regulatory cells and antibody responses in transplantation. Transplantation. 2018 Oct;102(10):1614–1623. PubMed PMID: 29757907.
  • Sayin I, Radtke AJ, Vella LA, et al. Spatial distribution and function of T follicular regulatory cells in human lymph nodes. J Exp Med. 2018 Jun 4;215(6):1531–1542. PubMed PMID: 29769249.
  • Karahan GE, Claas FH, Heidt S. B cell immunity in solid organ transplantation. Front Immunol. 2016;7:686. PubMed PMID: 28119695.
  • Chhabra M, Alsughayyir J, Qureshi MS, et al. Germinal center alloantibody responses mediate progression of chronic allograft injury. Front Immunol. 2018;9:3038. PubMed PMID: 30728823.
  • Shrestha BM. Two decades of tacrolimus in renal transplant: basic science and clinical evidences. Exp Clin Transplant. 2017 Feb;15(1):1–9. PubMed PMID: 27938316.
  • Vafadari R, Kraaijeveld R, Weimar W, et al. Tacrolimus inhibits NF-kappaB activation in peripheral human T cells. PLoS One. 2013;8(4):e60784. PubMed PMID: 23573283.
  • Laskin BL, Jiao J, Baluarte HJ, et al. The effects of tacrolimus on T-cell proliferation are short-lived: a pilot analysis of immune function testing. Transplant Direct. 2017;3(8):e199–e199. PubMed PMID: 28795150; eng.
  • de Graav GN, Dieterich M, Hesselink DA, et al. Follicular T helper cells and humoral reactivity in kidney transplant patients. Clin Exp Immunol. 2015 May;180(2):329–340. PubMed PMID: 25557528.
  • Wallin EF, Hill DL, Linterman MA, et al. The calcineurin inhibitor tacrolimus specifically suppresses human T follicular helper cells. Front Immunol. 2018;9:1184. PubMed PMID: 29904381.
  • Iwasaki K, Kitahata N, Hiramitsu T, et al. Increased CD40L+PD-1+ follicular helper T cells (Tfh) as a biomarker for predicting calcineurin inhibitor sensitivity against Tfh-mediated B-cell activation/antibody production after kidney transplantation. Int Immunol. 2018 Jul 24;30(8):345–355. PubMed PMID: 29878122.
  • Heidt S, Roelen DL, Eijsink C, et al. Calcineurin inhibitors affect B cell antibody responses indirectly by interfering with T cell help. Clin Exp Immunol. 2010 Feb;159(2):199–207. PubMed PMID: 19922499.
  • De Bruyne R, Bogaert D, De Ruyck N, et al. Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells. Clin Exp Immunol. 2015 Jun;180(3):542–550. PubMed PMID: 25682989.
  • Clatworthy MR. B cell modulation in transplantation. Clin Exp Immunol. 2014 Dec;178(Suppl 1):61–63. PubMed PMID: 25546764.
  • Heidt S, Roelen DL, Eijsink C, et al. Effects of immunosuppressive drugs on purified human B cells: evidence supporting the use of MMF and rapamycin. Transplantation. 2008 Nov 15;86(9):1292–1300. PubMed PMID: 19005412.
  • Thaunat O, Koenig A, Leibler C, et al. Effect of immunosuppressive drugs on humoral allosensitization after kidney transplant. J Am Soc Nephrol. 2016 Jul;27(7):1890–1900. PubMed PMID: 26872489.
  • Traitanon O, Mathew JM, La Monica G, et al. Differential effects of tacrolimus versus sirolimus on the proliferation, activation and differentiation of human B cells. PLoS One. 2015;10(6):e0129658. PubMed PMID: 26087255.
  • Davis S, Gralla J, Klem P, et al. Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor-specific antibodies in the first year of kidney transplantation. Am J Transplant. 2018 Apr;18(4):907–915. PubMed PMID: 28925597.
  • Pizzo HP, Ettenger RB, Gjertson DW, et al. Sirolimus and tacrolimus coefficient of variation is associated with rejection, donor-specific antibodies, and nonadherence. Pediatr Nephrol. 2016 Dec;31(12):2345–2352. PubMed PMID: 27286686.
  • Rodrigo E, Segundo DS, Fernandez-Fresnedo G, et al. Within-patient variability in tacrolimus blood levels predicts kidney graft loss and donor-specific antibody development. Transplantation. 2016 Nov;100(11):2479–2485. PubMed PMID: 26703349.
  • Gatault P, Kamar N, Buchler M, et al. Reduction of extended-release tacrolimus dose in low-immunological-risk kidney transplant recipients increases risk of rejection and appearance of donor-specific antibodies: a randomized study. Am J Transplant. 2017 May;17(5):1370–1379. PubMed PMID: 27862923.
  • Wiebe C, Rush DN, Nevins TE, et al. Class II eplet mismatch modulates tacrolimus trough levels required to prevent donor-specific antibody development. J Am Soc Nephrol. 2017;28(11):3353–3362. PubMed PMID: 28729289.
  • Tambur AR, Campbell P, Claas FH, et al. Sensitization in transplantation: assessment of risk (STAR) 2017 working group meeting report. Am J Transplant. 2018 Jul;18(7):1604–1614. PubMed PMID: 29603613.
  • Montgomery RA, Lonze BE, King KE, et al. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med. 2011 Jul 28;365(4):318–326. PubMed PMID: 21793744.
  • Kosmoliaptsis V, Mallon DH, Chen Y, et al. Alloantibody responses after renal transplant failure can be better predicted by donor-recipient HLA amino acid sequence and physicochemical disparities than conventional HLA matching. Am J Transplant. 2016 Jul;16(7):2139–2147. PubMed PMID: 26755448.
  • Wiebe C, Nickerson P. Strategic use of epitope matching to improve outcomes. Transplantation. 2016 Oct;100(10):2048–2052. PubMed PMID: 27362311.
  • Jung H-Y, Kim S-H, Seo M-Y, et al. Characteristics and clinical significance of De Novo donor-specific anti-HLA antibodies after kidney transplantation. J Korean Med Sci. 2018;33(34):e217–e217. PubMed PMID: 30127706.
  • Girerd S, Schikowski J, Girerd N, et al. Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014. BMC Nephrol. 2018;19(1): 232–232. PubMed PMID: 30219043.
  • Kaya Aksoy G, Comak E, Koyun M, et al. Tacrolimus variability: a cause of donor-specific anti-HLA antibody formation in children. Eur J Drug Metab Pharmacokinet. 2019 Feb 8;44:539–548. PubMed PMID: 30737655.
  • Beland MA, Lapointe I, Noel R, et al. Higher calcineurin inhibitor levels predict better kidney graft survival in patients with de novo donor-specific anti-HLA antibodies: a cohort study. Transpl Int. 2017 May;30(5):502–509. PubMed PMID: 28186642.
  • Rozen-Zvi B, Schneider S, Lichtenberg S, et al. Association of the combination of time-weighted variability of tacrolimus blood level and exposure to low drug levels with graft survival after kidney transplantation. Nephrol Dial Transplant. 2017 Feb 1;32(2):393–399. PubMed PMID: 28025383.
  • Tholking G, Fortmann C, Koch R, et al. The tacrolimus metabolism rate influences renal function after kidney transplantation. PLoS One. 2014;9(10):e111128. PubMed PMID: 25340655.
  • Schutte-Nutgen K, Tholking G, Steinke J, et al. Fast Tac metabolizers at risk (-) it is time for a C/D ratio calculation. J Clin Med. 2019 Apr 28;8(5):587. PubMed PMID: 31035422.
  • Jouve T, Fonrose X, Noble J, et al. The TOMATO study (TacrOlimus MetabolizAtion in kidney TransplantatiOn): impact of the concentration-dose ratio on death-censored graft survival. Transplantation. 2019 Aug 12:1. PubMed PMID: 31415035.
  • Kaneku H, O’Leary JG, Banuelos N, et al. De novo donor-specific HLA antibodies decrease patient and graft survival in liver transplant recipients. Am J Transplant. 2013 Jun;13(6):1541–1548. PubMed PMID: 23721554.
  • Del Bello A, Congy-Jolivet N, Danjoux M, et al. High tacrolimus intra-patient variability is associated with graft rejection, and de novo donor-specific antibodies occurrence after liver transplantation. World J Gastroenterol. 2018 Apr 28;24(16):1795–1802. PubMed PMID: 29713132.
  • Vandevoorde K, Ducreux S, Bosch A, et al. Prevalence, risk factors, and impact of donor-specific alloantibodies after adult liver transplantation. Liver Transpl. 2018 Aug;24(8):1091–1100. PubMed PMID: 29665189.
  • Van Der Veer MAA, Nangrahary N, Hesselink DA, et al. High intra-patient variability in tacrolimus exposure is not associated with immune-mediated graft injury after liver transplantation. Transplantation. 2019 Feb 19;103:2329–2337. PubMed PMID: 30801539.
  • O’Leary JG, Samaniego M, Barrio MC, et al. The influence of immunosuppressive agents on the risk of De Novo donor-specific HLA antibody production in solid organ transplant recipients. Transplantation. 2016 Jan;100(1):39–53. PubMed PMID: 26680372.
  • Budde K, Zeier M, Witzke O, et al. Everolimus with cyclosporine withdrawal or low-exposure cyclosporine in kidney transplantation from month 3: a multicentre, randomized trial. Nephrol Dial Transplant. 2017 Jun 1;32(6):1060–1070. PubMed PMID: 28605781.
  • Liefeldt L, Brakemeier S, Glander P, et al. Donor-specific HLA antibodies in a cohort comparing everolimus with cyclosporine after kidney transplantation. Am J Transplant. 2012 May;12(5):1192–1198. PubMed PMID: 22300538.
  • Rostaing L, Hertig A, Albano L, et al. Fibrosis progression according to epithelial-mesenchymal transition profile: a randomized trial of everolimus versus CsA. Am J Transplant. 2015 May;15(5):1303–1312. PubMed PMID: 25808994.
  • Huang Y, Ramon D, Luan FL, et al. Incidences of preformed and de novo donor-specific HLA antibodies and their clinicohistological correlates in the early course of kidney transplantation. Clin Transplant. 2012:247–256. PubMed PMID: 23721029.
  • Kamar N, Del Bello A, Congy-Jolivet N, et al. Incidence of donor-specific antibodies in kidney transplant patients following conversion to an everolimus-based calcineurin inhibitor-free regimen. Clin Transplant. 2013 May-Jun;27(3):455–462. PubMed PMID: 23621682.
  • Jouve T, Noble J, Rostaing L, et al. Tailoring tacrolimus therapy in kidney transplantation. Expert Rev Clin Pharmacol. 2018 Jun;11(6):581–588. PubMed PMID: 29779413.
  • Shuker N, Bouamar R, Hesselink DA, et al. Intrapatient variability in tacrolimus exposure does not predict the development of cardiac allograft vasculopathy after heart transplant. Exp Clin Transplant. 2018 Jun;16(3):326–332. PubMed PMID: 28969528.
  • Berger SP, Sommerer C, Witzke O, et al. Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study. Am J Transplant. 2019;19(11):3018–3034.
  • Hricik DE, Formica RN, Nickerson P, et al. Adverse outcomes of tacrolimus withdrawal in immune-quiescent kidney transplant recipients. J Am Soc Nephrol. 2015;26(12):3114–3122. PubMed PMID: 25925687.
  • Dugast E, Soulillou JP, Foucher Y, et al. Failure of calcineurin inhibitor (Tacrolimus) weaning randomized trial in long-term stable kidney transplant recipients. Am J Transplant. 2016 Nov;16(11):3255–3261. PubMed PMID: 27367750.
  • Hage V, Ferrandiz I, Belliere J, et al. Incidence of donor-specific anti-HLA antibodies in non-HLA-sensitized patients given tacrolimus once or twice daily during the first 2 years after kidney transplant. Exp Clin Transplant. 2018 Dec 31;17(3):313-319. PubMed PMID: 30602364.