About 1 million people in the US have End Stage Renal Disease (ESRD). Treatment is divided roughly 70/30 between dialysis and kidney transplantation. The annual cost of the ESRD program, almost all of which is funded by Medicare, is more than $48 billion. It costs about $89,000 a year to care for a dialysis patient. The cost of caring for a kidney transplant patient after the first year post-op is far less, approximately $25,000. Thus, kidney transplantation is often touted as being more cost effective than dialysis. But the first year costs likely exceed $260, 000. These costs are billed charges, Medicare may pay less. The average survival on dialysis is about 6 years. As about 20% of transplanted kidneys fail, the cost differential favoring kidney transplantation over dialysis is real, but not as great as is often advertised. What is indisputable is that the quality of life for a patient with a successful transplant is far greater than for a dialysis patient.
About 15,000 patients are on the waiting list for a transplant, but only about 15% will receive a transplant of which about a third are from living donors. One of the limiting factors for transplanting kidneys from living donors is that increasing numbers of waitlisted patients have HLA sensitization. If such patients have specific HLA antibodies against the donor (i.e., donor-specific alloantibodies), then there is a risk of antibody-mediated rejection, which inexorably leads to loss of the grafted kidney.
In the March 10, 2016 issue of The New England Journal of Medicine, Orandi and colleagues present a collaborative study, Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors, which examined the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting- list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group).
This is an important paper that is presented in a remarkably opaque fashion suggesting that the editors and/or reviewers at the NEJM were not up to their usual game. What was done to counter the problem of HLA-incompatibility? It was not included in the abstract. If you move to the Methods section of the paper you find this: “Recipients of kidney transplants from HLA-incompatible live donors were defined as those undergoing perioperative desensitization therapy for donor-specific antibodies detected before transplantation, as previously defined.(25)” Thus they were desensitized. Reference 25 doesn’t describe how these patients were desensitized, nor does the rest of the paper. Desensitization may be accomplished by strong immunosuppression and antibody clearance with the use of apheresis (e.g., immunoadsorption 6 and plasmapheresis) and B-cell modulating therapies (e.g., administration of high-dose immune globulins or rituximab). Desensitization may also include plasma-cell depletion (with bortezomib) 7 and complement inhibition (with eculizumab).
So we’ll assume desensitization was successfully accomplished by whatever means, what happened then? The figure below summarizes the study’s findings.
As is obvious, the desensitized patients who received an incompatible transplant had a better survival rate than did the two control groups. Not presented are data from patients who received kidneys from donors that were not incompatible or data on graft survival. This study strongly indicates that with proper desensitization kidneys can be given to recipients with HLA antibodies against the donors and thus increase the number of patients with ESRD treated with a medically superior modality. It will be interesting to see if the number of transplants increases in the US over the next few years.