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.Clin J Am Soc Nephrol 11: 684-693, 2016. doi: 10.2215/CJN.05930615 Case PresentationA 38-year-old black man with type 2 diabetes and ESRD due to diabetic nephropathy presented for evaluation for a second kidney transplant. He was receiving hemodialysis for 1 year before undergoing his first deceased-donor kidney transplant in 1997. His immediate post-transplant course was uncomplicated, without known episodes of rejection. The graft began to fail about 4 years before his resumption of dialysis. A renal allograft biopsy at that time showed calcineurin inhibitor toxicity and chronic allograft nephropathy but no acute rejection. He resumed peritoneal dialysis in 2010, at which time his immunosuppression was weaned to low-dose prednisone, 5 mg daily. He is blood type A, which portends wait times of 3-4 years in our organ procurement organization (OPO), the geographically defined unit of organ allocation. An historical panel-reactive antibody (PRA) on full immunosuppression was 0% but repeat testing at current evaluation reveals a calculated panel-reactive antibody (cPRA) of 100% with multiple HLA antibodies against class II antigens. See candidate HLA t...

Immunoglobulin G–Degrading Enzyme of Streptococcus pyogenes (IdeS), Desensitization, and the Kidney Allocation System

“…Patients with calculated panel reactive antibodies $99.95% accounted for 34.0% of candidates with calculated panel reactive antibodies $99% (approximately 2700 candidates in the United States) but received only 8% of the transplants for those with calculated panel reactive antibodies $99% in the first year after the KAS was implemented (3). For any given calculated panel reactive antibodies percentage, the probability of finding an acceptable match can be estimated with the following formula: 12 (calculated panel reactive antibodies percentage) n , where n is the number of potential donors (4). Using this formula, candidates with calculated panel reactive antibodies of 99.95% would need approximately 6000 match runs to have a 95% probability of an acceptable crossmatch.…”

Desensitization protocols for prospective pediatric renal transplant recipients

“…There is increasing evidence in the literature that kidney transplant offers significant survival and quality-of-life advantages compared to dialysis, but that waiting times are long with limited options for highly sensitized patients [6,7]. Adults who receive kidney transplants from HLAi live donors have a substantial survival benefit as compared to patients who do not undergo transplantation and those who wait for transplants from deceased donors [8,9].…”

Desensitization strategies: is it worth it?

“…Four transplant possibilities are currently available for this disadvantaged group of dialysis patients. The first is to wait for a compatible deceased donor transplant, which may take years without a suitable donor ever being identified . It is estimated that patients with a cPRA of 100% must be offered in excess of 300 000 donor organs before finding one that would lead to a negative crossmatch.…”

“…It is estimated that patients with a cPRA of 100% must be offered in excess of 300 000 donor organs before finding one that would lead to a negative crossmatch. . Fortunate ones who have a living donor can undergo transplantation if the immunological barrier can be successfully crossed (option 2).…”