Correspondence

Desensitization during Renal Transplantation

N Engl J Med 2008; 359:1731-1732October 16, 2008

Article

To the Editor:

In their article on desensitization during renal transplantation (July 17 issue), Vo et al.1 report very encouraging results of desensitization with a rather simple and short protocol that combines two doses of intravenous immune globulin and rituximab in highly sensitized renal-transplant candidates. Although the administration of high-dose rituximab seems to have played a major role in the favorable outcomes, the type of immune globulin used in this protocol, not described in detail, should not be discounted. The efficacy of different intravenous immune globulin preparations may vary substantially in vitro2 and probably in vivo. This might be why many transplantation centers have not been able to reproduce the initial good results of other previously described desensitization protocols that used intravenous immune globulin. These variations in efficacy may become apparent not only for products from different manufacturers but also for batches from the same company, as a reflection of the different healthy-donor pool used for each batch. This is a very important issue for anyone who might consider trying the protocol by Vo et al. for sensitized patients undergoing dialysis.

Costas Fourtounas, M.D.
Athanasia Mouzaki, Ph.D.
Jannis G. Vlachojannis, M.D.
Patras University Hospital, 26500 Patras, Greece
cfourt@usa.net

2 References

1. 1

   Vo AA, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 2008;359:242-251
   Full Text | Web of Science | Medline

2. 2

   Clark B, Cole JY, Wortley A, et al. Intravenous immunoglobulin-induced panel reactive antibody A reduction: not all preparations are created equal. Transplantation 2003;75:242-245
   CrossRef | Web of Science | Medline

Author/Editor Response

Fourtounas et al. note the role of intravenous immune globulin in desensitization and the potential variation in efficacy among intravenous immune globulin products. All major intravenous immune globulin products are derived from plasma pooled from thousands of donors. Thus, it seems unlikely that variation in antibody repertoire and efficacy would occur. Indeed, in our experience using various products for desensitization in several hundred patients and in in vitro studies, there have been no discernible differences.1,2

Our data also show that most patients did not have a completely negative cross-match by the time of transplantation. Thus, one has to be prepared to perform transplantation in patients in whom donor-specific antibodies have been reduced but not eliminated. We also believe that using a combination of flow cytometry and monitoring of donor-specific antibodies helps predict the efficacy of desensitization.3

In summary, it is our opinion that intravenous immune globulin products from all major manufacturers probably have similar efficacy with regard to desensitization. Intravenous immune globulin has other immunomodulatory actions that should aid in desensitization.4 The addition of rituximab may also improve the chances for successful desensitization.

Stanley C. Jordan, M.D.
Ashley A. Vo, Pharm.D.
Nancy L. Reinsmoen, Ph.D.
Cedars–Sinai Medical Center, Los Angeles, CA 90048
sjordan@cshs.org

4 References

1. 1

   Vo A, Cam V, Toyoda M, et al. Safety and adverse event profiles of intravenous gammaglobulin products used for immunomodulation: a single-center experience. Clin J Am Soc Nephrol 2006;1:844-852
   CrossRef | Web of Science | Medline

2. 2

   Toyoda M, Pao A, Petrosian A, Jordan SC. Pooled human gammaglobulin modulates surface molecule expression and induces apoptosis in human B cells. Am J Transplant 2003;3:156-166
   CrossRef | Web of Science | Medline

3. 3

   Reinsmoen N, Lai C, Vo A, et al. Acceptable donor-specific antibody levels allowing for successful deceased and living donor kidney transplantation after desensitization therapy. Transplantation (in press).
   

4. 4

   Kaveri SV, Lacroix-Desmazes S, Bayry J. The antiinflammatory IgG. N Engl J Med 2008;359:307-309
   Full Text | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Weijie Zhang, Dong Chen, Zhishui Chen, Fanjun Zeng, Changsheng Ming, Zhengbin Lin, Ping Zhou, Gang Chen, Xiaoping Chen. (2011) Successful kidney transplantation in highly sensitized patients. Frontiers of Medicine 5:1, 80-85
   CrossRef