全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

Effects of Rituximab on the Development of Viral and Fungal Infections in Renal Transplant Recipients

DOI: 10.5402/2013/819025

Full-Text   Cite this paper   Add to My Lib

Abstract:

Background. Rituximab is becoming increasingly utilized in renal transplant recipients; however, its association with infections remains unclear. Methods. We reviewed the incidence of viral and fungal infections in kidney transplant recipients treated with ( ) or without ( ) rituximab (RTX) in addition to standard immunosuppression. Results. Infections occurred in 134 (30%) patients, with a greater proportion in RTX versus no RTX patients (47% versus 28%; ). Viral infections occurred in 44% and 27% of RTX and no RTX patients, respectively ( ). This was largely driven by the frequency of BK viremia and noncytomegalovirus/non-BK viruses in RTX patients (27% versus 13% ( ) and 15% versus 2% ( ), resp.). Fungal infections also occurred more often in RTX patients (11% versus 3 %; ). Multivariate analysis revealed deceased donor recipient (odds ratio = 2.5; ) and rituximab exposure (odds ratio = 2.2; ) as independent risk factors for infection. Older patients, deceased donor recipients, those on dialysis longer, and those with delayed graft function tended to be at a greater risk for infections following rituximab. Conclusions. Rituximab is associated with an increased incidence of viral and fungal infections in kidney transplantation. Additional preventative measures and/or monitoring infectious complications may be warranted in those receiving rituximab. 1. Introduction The anti-CD20 monoclonal antibody rituximab (RTX) has become a more widely utilized therapy in the renal transplant population. RTX use has expanded from treatment of posttransplant lymphoproliferative disease to facilitation of ABO-incompatible transplantation, reduction of human leukocyte antigen (HLA) antibodies in highly sensitized patients, treatment of antibody mediated rejection (AMR), and treatment of recurrent and de novo renal diseases [1–4]. Each of these conditions represents a significant challenge in renal transplantation by which B-cell depletion with RTX may represent a promising intervention. It is well known that, with more potent immune suppression, the risk of infectious complications after transplant increases. T-lymphocyte depleting preparations in particular have been associated with an increased risk, as opposed to nonlymphocyte depleting agents which demonstrated similar infectious risks when compared to placebo [5, 6]. RTX has generally been considered to have an acceptable safety profile in hematological and autoimmune disorders; however, whether it can be used without an increased risk of infectious complications remains controversial in the immunosuppressed

References

[1]  M. D. Pescovitz, “Rituximab, an anti-CD20 monoclonal antibody: history and mechanism of action,” The American Journal of Transplantation, vol. 6, no. 5, part 1, pp. 859–866, 2006.
[2]  Y. T. Becker, M. Samaniego-Picota, and H. W. Sollinger, “The emerging role of rituximab in organ transplantation,” Transplant International, vol. 19, no. 8, pp. 621–628, 2006.
[3]  A. A. Vo, M. Lukovsky, M. Toyoda et al., “Rituximab and intravenous immune globulin for desensitization during renal transplantation,” The New England Journal of Medicine, vol. 359, no. 3, pp. 242–251, 2008.
[4]  H. Genberg, G. Kumlien, L. Wennberg, U. Berg, and G. Tydén, “ABO-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab: a 3-year follow-up,” Transplantation, vol. 85, no. 12, pp. 1745–1754, 2008.
[5]  G. L. Bumgardner, I. Hardie, R. W. G. Johnson et al., “Results of 3-year phase III clinical trials with daclizumab prophylaxis for prevention of acute rejection after renal transplantation,” Transplantation, vol. 72, no. 5, pp. 839–845, 2001.
[6]  B. Nashan, R. Moore, P. Amlot, A.-G. Schmidt, K. Abeywickrama, and J.-P. Soulillou, “Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients,” The Lancet, vol. 350, no. 9086, pp. 1193–1198, 1997.
[7]  S. A. Grim, T. Pham, J. Thielke et al., “Infectious complications associated with the use of rituximab for ABO-incompatible and positive cross-match renal transplant recipients,” Clinical Transplantation, vol. 21, no. 5, pp. 628–632, 2007.
[8]  N. Kamar, O. Milioto, B. Puissant-Lubrano et al., “Incidence and predictive factors for infectious disease after rituximab therapy in kidney-transplant patients,” The American Journal of Transplantation, vol. 10, no. 1, pp. 89–98, 2010.
[9]  A. S. Munoz, A. A. Rioveros, C. B. Cabanayan-Casasola, R. A. Danguilan, and E. T. Ona, “Rituximab in highly sensitized kidney transplant recipients,” Transplantation Proceedings, vol. 40, no. 7, pp. 2218–2221, 2008.
[10]  Z. Kaposztas, H. Podder, S. Mauiyyedi et al., “Impact of rituximab therapy for treatment of acute humoral rejection,” Clinical Transplantation, vol. 23, no. 1, pp. 63–73, 2009.
[11]  A. Habicht, V. Br?ker, C. Blume et al., “Increase of infectious complications in ABO-incompatible kidney transplant recipients-a single centre experience,” Nephrology Dialysis Transplantation, vol. 26, no. 12, pp. 4124–4131, 2011.
[12]  C. H. Baek, W. S. Yang, K. S. Park, D. J. Han, J. B. Park, and S. K. Park, “Infectious risks and optimal strength of maintenance immunosuppressants in rituximab-treated kidney transplantation,” Nephron Extra, vol. 2, no. 1, pp. 66–75, 2012.
[13]  G. Tydén, H. Genberg, J. Tollemar et al., “A randomized, doubleblind, placebo-controlled, study of single-dose rituximab as induction in renal transplantation,” Transplantation, vol. 87, no. 9, pp. 1325–1329, 2009.
[14]  J. Kahwaji, A. Sinha, M. Toyoda et al., “Infectious complications in kidney-transplant recipients desensitized with rituximab and intravenous immunoglobulin,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 12, pp. 2894–2900, 2011.
[15]  Thymoglobulin (Anti-thymocyte globulin rabbit), Package Insert, Genzyme, Cambridge, Mass, USA.
[16]  H. Genberg, A. Hansson, A. Wernerson, L. Wennberg, and G. Tydén, “Pharmacodynamics of rituximab in kidney transplantation,” Transplantation, vol. 84, supplement 12, pp. S33–S36, 2007.
[17]  C. A. Vieira, A. Agarwal, B. K. Book et al., “Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation: 1. Safety, pharmacodynamics, and pharmacokinetics1,” Transplantation, vol. 77, no. 4, pp. 542–548, 2004.
[18]  I. A. Memon, B. A. Parikh, M. Gaudreault-Keener, R. Skelton, G. A. Storch, and D. C. Brennan, “Progression from sustained BK viruria to sustained BK viremia with immunosuppression reduction is not associated with changes in the noncoding control region of the BK virus genome,” Transplantation, vol. 2012, Article ID 761283, 7 pages, 2012.
[19]  H. H. Hirsch, D. C. Brennan, C. B. Drachenberg et al., “Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations,” Transplantation, vol. 79, no. 10, pp. 1277–1286, 2005.
[20]  D. C. Brennan, I. Agha, and D. L. Bohl, “Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction,” The American Journal of Transplantation, vol. 5, no. 3, pp. 582–594, 2005.
[21]  E. Ramos, C. B. Drachenberg, R. Wali, and H. H. Hirsch, “The decade of polyomavirus BK-associated nephropathy: state of affairs,” Transplantation, vol. 87, no. 5, pp. 621–630, 2009.
[22]  A. Bermúdez, F. Marco, E. Conde, E. Mazo, M. Recio, and A. Zubizarreta, “Fatal visceral varicella-zoster infection following rituximab and chemotherapy treatment in a patient with follicular lymphoma,” Haematologica, vol. 85, no. 8, pp. 894–895, 2000.
[23]  L. M. Mcilwaine, E. J. Fitzsimons, and R. L. Soutar, “Inappropriate antidiuretic hormone secretion, abdominal pain and disseminated varicella-zoster virus infection: an unusual and fatal triad in a patient 13 months post Rituximab and autologous stem cell transplantation,” Clinical and Laboratory Haematology, vol. 23, no. 4, pp. 253–254, 2001.
[24]  E. Irie, Y. Shirota, C. Suzuki et al., “Severe hypogammaglobulinemia persisting for 6 years after treatment with rituximab combined chemotherapy due to arrest of B lymphocyte differentiation together with alteration of T lymphocyte homeostasis,” International Journal of Hematology, vol. 91, no. 3, pp. 501–508, 2010.
[25]  N. Cooper, E. G. Davies, and A. J. Thrasher, “Repeated courses of rituximab for autoimmune cytopenias may precipitate profound hypogammaglobulinaemia requiring replacement intravenous immunoglobulin,” British Journal of Haematology, vol. 146, no. 1, pp. 120–122, 2009.
[26]  S. Mawhorter and M. H. Yamani, “Hypogammaglobulinemia and infection risk in solid organ transplant recipients,” Current Opinion in Organ Transplantation, vol. 13, no. 6, pp. 581–585, 2008.
[27]  S. Hariharan, E. P. Cohen, B. Vasudev et al., “BK virus-specific antibodies and BKV DNA in renal transplant recipients with BKV nephritis,” The American Journal of Transplantation, vol. 5, no. 11, pp. 2719–2724, 2005.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133