Doc, I am very sensitized! (part 2)

Let’s continue our discussion from our last blog about sensitized kidney recipients. In summary, we have this 60 yo man interested on a second transplant. He has a high PRA (98%) as well as anti-HLA Abs against his only potential donor (his son).

So, what is his best option? His best outcome would be to obtain a kidney from a donor that he does not have any HLA Abs against (DSA). If he waits in the deceased donor list, this might take many years based on his elevated PRA (most kidneys from the population will have HLAs that he is sensitized to). Similar problem would be faced by enlisting on a paired kidney donation (PKD) program, since he will likely be sensitized to most of the donors. However, this has a great potential in near future since the larger the size of the enrolled pool of recipients, the greatest the chance of success in finding a donor.

Finally, we could attempt to desensitize our kidney recipient so that he could get a kidney from his son. The best predictor of success in desensitizing a patient is his titers of DSA. The general literature suggests that the higher the titer the lower the success in obtaining a negative crossmatch pretransplantation (ultimate goal). There are two major protocols of desensitization:

-high dose IVIG (2g/kg)
-Plasmapheresis associated with low dose IVIG (100mg/kg).

The goal of desensitization is to decrease the number of circulating DSA and decrease the production of these Abs, preventing hyperacute rejection in the immediate posttransplant period and minimizing the risk of subacute antibody-mediated rejection (AMR). Plasmapheresis (TPE) is able to remove physically the antibodies, however is associated with great rebound of antibodies if used alone. IVIG is effective in reducing anti-HLA Abs, through multiple hypothesized mechanisms (Figure above). There has been no randomized trials comparing both protocols, however a retrospective analysis suggested that combination of IVIG with TPE might be more effective in desensitizing patients. Even though both protocols are able to reduce hyperacute rejection and decrease DSA in most patients, they are not effective in patients with high titers of DSA and they are still associated with high prevalence of AMR (20-50%) after transplantation. The presence of AMR significantly decreases long-term graft survival . Moreover, the combination TPE and IVIG is impractical for deceased kidney transplantation, leaving high dose IVIG as the only option for those patients without potential living donors. Finally, Rituximab has been added in some protocols with some good additional results.

In our patient, the DSA titers were low at 1:4 and repeat DSA was 82%. Our recommendation was to enlist him on a paired kidney donation as well as deceased donor list (he gets extra points for his high PRA). We would also start preparing him for a potential desensitization in case no donors were available in the PKD program. A combination of TPE and low dose IVIG is used in our center and we estimate a minimal of 4 TPE before obtaining a negative AHG-CDC crossmatch (based on titers). Immunosuppressive drugs are started 4 days prior to potential tx day. Lastly, we would also perform a minimum of 3 sessions of TPE after tx with IVIG, followed by monitoring for DSA. Based on our own’s center data, we expect a good short-term outcome on his case with ~90% graft survival on the first year after transplant. Long-term is still suboptimal due to high degree of AMR with all available protocols, but with better survival then staying on dialysis.