Approach to the Highly Sensitized Kidney Transplant Candidate

Abstract

For patients with ESRD, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, wait times have traditionally been long and options limited. The approach to the highly sensitized candidate for kidney transplant has changed substantially over time owing to new advances in desensitization, options for paired donor exchange (PDE), and changes to the deceased-donor allocation system. Initial evaluation should focus on determining living-donor availability because a compatible living donor is always the best option. However, for most highly sensitized candidates this scenario is unlikely. For candidates with an incompatible donor, PDE can improve the prospects of finding a compatible living donor but for many highly sensitized patients the probability of finding a match in the relatively small pools of donors in PDE programs is limited. Desensitization of a living donor/recipient pair with low levels of incompatibility is another reasonable approach. But for pairs with high levels of pathologic HLA antibodies, outcomes after desensitization for the patient and allograft are less optimal. Determining the degree of sensitization by calculated panel-reactive antibody (cPRA) is critical in counseling the highly sensitized patient on expected wait times to deceased-donor transplant. For candidates with a high likelihood of finding a compatible deceased donor in a reasonable time frame, waiting for a kidney is a good strategy. For the candidate without a living donor and with a low probability of finding a deceased-donor match, desensitization on the waiting list can be considered. The approach to the highly sensitized kidney transplant candidate must be individualized and requires careful discussion among the transplant center, patient, and referring nephrologist.

Keywords: HLA antigens; allografts; chronic’ living donors; humans; immunology; kidney; kidney failure; kidney transplantation; quality of life; renal dialysis.

Figure 1.

Algorithm for the management of the highly sensitized patient seeking kidney transplant. ^‡There is no predefined level of incompatibility that is considered insurmountable and decision to pursue desensitization should be individualized for the potential recipient considering medical eligibility, degree of sensitization to the donor, and financial coverage. This decision making is highly center specific. The risks of early graft failure are significantly increased in those pairs with positive CDC crossmatch prior to desensitization and pursuing living donor transplantation in this setting should be attempted with caution. Paired donor exchange may offer candidates the opportunity to seek a more compatible donor, possibly obviating the risks and costs associated with desensitization (14). CDC, complement-dependent cytotoxicity.

Figure 2.

Distribution of calculated panel-reactive antibody (cPRA) values for sensitized candidates on the waiting list for kidney transplantation in the United States as of August 31, 2013 in the Scientific Registry of Transplant Recipients. The distribution of sensitization levels among candidates with a cPRA≥1% is not uniform. More than 20% of sensitized candidates have measured cPRA levels ≥95%.

Figure 3.

Allocation points by calculated panel-reactive antibody (cPRA) in the old versus new kidney allocation system. Candidates listed for kidney transplant receive one point for each year on the list. Under the old kidney allocation system, candidates with cPRA scores >80% received four additional allocation points. Under the new allocation system, additional points are awarded for sensitization on a sliding scale. Candidates with cPRA scores of 98%, 99%, and 100% receive 24.4, 50.1, and 202.1 points respectively.

Figure 4.

All-cause kidney allograft loss based on crossmatch and donor-specific antibody results. All-cause graft loss, by antibody strength. PCC, positive cytotoxic crossmatch; PFNC, positive flow, negative cytotoxic crossmatch; PLNF, positive Luminex, negative flow crossmatch. Reprinted from Orandi et al. (14), with permission.