J Korean Surg Soc.  2012 Jun;82(6):335-339.

Impact of pretransplant rituximab induction on highly sensitized kidney recipients: comparison with non-rituximab group

• Song YH
• Huh KH
• Kim YS
• Lee HS
• Kim MS
• Kim SJ
• Kim HJ
• Kim SI
• Joo DJ

Abstract

PURPOSE
Highly sensitized patients with a high level of panel reactive antibody (PRA) experience more episodes of antibody-mediated rejection (AMR) and poorer graft survival than non-sensitized patients. Rituximab is a well-known monoclonal anti-CD20 antibody that causes the depletion of B lymphocytes. The aim of this study was to compare a rituximab-administered and a non-administered group of highly sensitized recipients.
METHODS
Forty-three kidney recipients with a PRA level of > or =50% were included. Sixteen (group R) received one dose of rituximab at 2 days prior to transplantation and 27 patients (group NR) did not.
RESULTS
Patients' demographics, such as age, sex, dialysis duration, and type of immunosuppressive agent were not different in the two groups. No side effects due to rituximab administration were observed in group R. Class I PRA of group R (75.6 +/- 37.7%) was higher than that of group NR (45.7 +/- 35.8%, P = 0.013). More acute rejection episodes occurred within 1 year after transplantation in group NR but the difference between the groups was not significant (18.8% in group R vs. 29.6% in group NR, P = 0.631). However, two AMR episodes occurred only in group NR. Renal functions were not different in the two groups. In group R, CD19 and CD20 rapidly decreased 2 days after rituximab infusion. Furthermore, the administration of rituximab was not linked to acute rejection.
CONCLUSION
To confirm the long-term anti-rejection and beneficial effects of rituximab, further studies should be performed with a larger cohort. In conclusion, rituximab administration 2 days prior to transplantation is both effective and safe.

Keyword

Kidney transplantation; Immunological sensitization; Rituximab

MeSH Terms

Antibodies, Monoclonal, Murine-Derived
B-Lymphocytes
Cohort Studies
Demography
Dialysis
Graft Survival
Humans
Immunization
Kidney
Kidney Transplantation
Rejection (Psychology)
Rituximab
Transplants
Antibodies, Monoclonal, Murine-Derived

Figure

• 

  Fig. 1 Changes in serum CD19 and CD20 after rituximab infusion. a)P < 0.05 compared with pre-rituximab status. b)P < 0.05 compared with 2 days after rituximab.

Reference

1. Jordan S, Cunningham-Rundles C, McEwan R. Utility of intravenous immune globulin in kidney transplantation: efficacy, safety, and cost implications. Am J Transplant. 2003. 3:653–664.

2. Jordan SC, Pescovitz MD. Presensitization: the problem and its management. Clin J Am Soc Nephrol. 2006. 1:421–432.

3. Iwaki Y, Terasaki PI. Sensitization effect. Clin Transpl. 1986. 257–265.

4. Crespo M, Pascual M, Tolkoff-Rubin N, Mauiyyedi S, Collins AB, Fitzpatrick D, et al. Acute humoral rejection in renal allograft recipients: I. Incidence, serology and clinical characteristics. Transplantation. 2001. 71:652–658.

5. Alausa M, Almagro U, Siddiqi N, Zuiderweg R, Medipalli R, Hariharan S. Refractory acute kidney transplant rejection with CD20 graft infiltrates and successful therapy with rituximab. Clin Transplant. 2005. 19:137–140.

6. Aranda JM Jr, Scornik JC, Normann SJ, Lottenberg R, Schofield RS, Pauly DF, et al. Anti-CD20 monoclonal antibody (rituximab) therapy for acute cardiac humoral rejection: a case report. Transplantation. 2002. 73:907–910.

7. Becker YT, Becker BN, Pirsch JD, Sollinger HW. Rituximab as treatment for refractory kidney transplant rejection. Am J Transplant. 2004. 4:996–1001.

8. Salama AD, Pusey CD. Drug insight: rituximab in renal disease and transplantation. Nat Clin Pract Nephrol. 2006. 2:221–230.

9. Sarwal M, Chua MS, Kambham N, Hsieh SC, Satterwhite T, Masek M, et al. Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N Engl J Med. 2003. 349:125–138.

10. Racusen LC, Colvin RB, Solez K, Mihatsch MJ, Halloran PF, Campbell PM, et al. Antibody-mediated rejection criteria: an addition to the Banff 97 classification of renal allograft rejection. Am J Transplant. 2003. 3:708–714.

11. Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant. 2006. 6:346–351.

12. Munoz AS, Rioveros AA, Cabanayan-Casasola CB, Danguilan RA, Ona ET. Rituximab in highly sensitized kidney transplant recipients. Transplant Proc. 2008. 40:2218–2221.

13. Vieira CA, Agarwal A, Book BK, Sidner RA, Bearden CM, Gebel HM, et al. Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation: 1. Safety, pharmacodynamics, and pharmacokinetics. Transplantation. 2004. 77:542–548.

14. Maloney DG, Grillo-López AJ, Bodkin DJ, White CA, Liles TM, Royston I, et al. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997. 15:3266–3274.

15. Faguer S, Kamar N, Guilbeaud-Frugier C, Fort M, Modesto A, Mari A, et al. Rituximab therapy for acute humoral rejection after kidney transplantation. Transplantation. 2007. 83:1277–1280.

16. Genberg H, Hansson A, Wernerson A, Wennberg L, Tydén G. Pharmacodynamics of rituximab in kidney allotransplantation. Am J Transplant. 2006. 6:2418–2428.

17. Yoon HE, Hyoung BJ, Hwang HS, Lee SY, Jeon YJ, Song JC, et al. Successful renal transplantation with desensitization in highly sensitized patients: a single center experience. J Korean Med Sci. 2009. 24:Suppl 1. S148–S155.

18. Toki D, Ishida H, Horita S, Setoguchi K, Yamaguchi Y, Tanabe K. Impact of low-dose rituximab on splenic B cells in ABO-incompatible renal transplant recipients. Transpl Int. 2009. 22:447–454.

19. Tyden G, Genberg H, Tollemar J, Ekberg H, Persson NH, Tufveson G, et al. A randomized, doubleblind, placebo-controlled, study of single-dose rituximab as induction in renal transplantation. Transplantation. 2009. 87:1325–1329.

20. Jilani I, O'Brien S, Manshuri T, Thomas DA, Thomazy VA, Imam M, et al. Transient down-modulation of CD20 by rituximab in patients with chronic lymphocytic leukemia. Blood. 2003. 102:3514–3520.

21. Cragg MS, Bayne MC, Illidge TM, Valerius T, Johnson PW, Glennie MJ. Apparent modulation of CD20 by rituximab: an alternative explanation. Blood. 2004. 103:3989–3990.