Renal transplantation has long been recognized as the treatment of choice for end-stage renal disease, as it offers improved quality of life and survival.  As a result, the demand for donor kidneys continues to outpace the supply and the ongoing organ shortage crisis persist. Currently, there are more than 96,538 ESRD patients on the deceased donor waiting list, and almost 30,000 new patients register annually, yet fewer than 16,680 kidney transplants were performed in 2011 (based on OPTN data as of March 2013). Unfortunately, the most rapidly growing aspect of kidney transplantation  is the number of patients who need one. As the demand for organs continues to exceed the supply, the number of days spent waiting for a kidney transplant increases exponentially, particularly for patients that are difficult to match secondary to having broadly reactive HLA-specific alloantibodies or difficult to match blood types.

The disparity in waiting time experienced by these patients is a by-product of an organ allocation policy adopted in the context of an ongoing organ shortage crisis, which dictates that deceased donor kidneys are allocated to blood type compatible recipients who have a negative complement- dependent cytotoxic crossmatch with their donor. A positive crossmatch (+CMX) indicates the presences of donor specific alloantibodies (DSA) in the serum of a potential recipient, and is associated with a rate of graft loss that exceeds 80%.  In addition, the development of de novo DSAs is associated with poor allograft outcomes long-term.  Alloantibodies develop following exposure to foreign HLA molecules, usually through pregnancy, transfusion, and or transplantation.

While local and national efforts to increase organ donation have had some success, the increase is unlikely to provide a large enough donor pool capable of supplying an ABO compatible and a perfectly matched donor for every potential recipient. The scarcity of donor organs has contributed to the disenfranchisement of this group of highly sensitized ESRD patients. Thus, in an effort to optimize organ availability and offer the benefit of renal transplantation to these patients, several transplant centers have developed protocols to overcome sensitization and blood group incompatibilities.

As a result of these efforts, it is now possible to perform successful renal transplantation in the presence of blood group incompatibilities and +CMX. Two main desensitization regimens are currently utilized - low-dose intravenous immunoglobulin (IVIG) with plasma exchange (PLEX) and high-dose IVIG. Low-dose IVIG/PLEX has been used successfully in live donor ABO incompatible and +CMX renal  transplantation, while high-dose IVIG has been used to desensitize both living-donor +CMX and highly-HLA sensitized deceased donor (DD) recipients from the waitlist.  High dose IVIG (2gm/kg) alone has been accepted as a reasonable approach to desensitization (-). Rituximab has emerged as an increasingly used agent in desensitization protocols. The B-cell depleting agent is often used in combination with high-dose IVIG and PLEX  + low-dose IVIG protocols.  Here we will discuss the options modification of antibody and B-cells as techniques to improve transplantation of sensitized patients.