Improving Access to Renal Transplantation for Highly Sensitized Patients.

Abstract

Transplantation is accepted to be the best form of treatment for end-stage renal disease, and it is also clear that the longer the patients wait on dialysis, the worse their overall graft and patient outcomes are, posttransplantation. The presence of increasing levels of anti-HLA antibodies progressively increases waiting times, especially highly sensitized patients (HSP) with panel reactivity (PRA) >85%. Currently, in the EuroTransplant (ET) allocation programs, the presence of antibody, even at a low level as detected by single antigen beads, generates a virtual PRA (vPRA). This results in unacceptable antigen matches so that offers are not made to these patients, increasing their expected wait time. ET allocates organs in three different systems. The Acceptable match program is successful in transplanting sensitized patients, but only a tiny percentage of potential recipients are eligible. The standard ET kidney allocation system integrates patients’ PRA into a mismatch probability (MMP), which generates additional points with the aim of assisting HSP to be transplanted. However, despite this, and partly because of the low donor rates in Germany, the median waiting time for patients with a vPRA of >95% is 13.2 y (and >10 y for patients with vPRA <95%). The ET senior programme that allocates kidneys on the basis of blood group, waiting time, and region (to minimize ischemic time) also disadvantages HSP. In this article, Zecher et al1 have analyzed the impact of vPRA levels of the various ET allocation systems in Germany and the factors disadvantaging HSP, including the effectiveness of the MMP to compensate for sensitization. Many of their findings are not surprising. For HSP, the higher their vPRA, the longer their median wait times are, except organs offered in the acceptable match system. This is only open to about 2% of patients, and the shorter waiting times reflect that the German patients in this program are in a pool with all ET countries, most of whom have much shorter waiting times. The MMP was designed to compensate for sensitization (as well as blood group and HLA type), and although incorporation of vPRA in 2020 did improve the correlation between vPRA and the score, the effect was not marked, and a high score could be generated with low or even zero vPRA. Furthermore, the maximum MMP score is only 100 out of a total of 800 points, thus limiting its efficacy to significantly reduce waiting times for HSP. The analysis of their cohort of patients on the waiting list, therefore, demonstrated that the MMP compensation was very inadequate. They also found that there was a high organ rejection rate in transplant centers for immunological reasons, suggesting inadequate or incorrect unacceptable antigen mismatches data provided to ET. Finally, the authors found large (> 2-fold) differences in the probability of transplantation between the 7 regions within Germany. This may partly be explained by variation in donation rate but is likely to represent different approaches to listing unacceptable antigen mismatches, including single antigen beads data. Clearly, HSP are and will always be disadvantaged by their sensitization, but in the interest of equity, their waiting times should be reduced as much as possible to improve long-term outcomes. Zecher et al1 highlight several important issues resulting in excessive waiting times, especially for HSP. There should be considerable scope to modify reporting of acceptable and unacceptable antigens to ET, and modification of the allocation algorithms could significantly improve waiting times for these severely disadvantaged patients. Comparison of individual center practice is also likely to identify factors that might reduce center and regional variation. German (and all ET) data could be used to model alterations to the allocation algorithms to improve waiting times for HSP and for better equity to other groups of patients, such as ethnic minorities. Lessons may be learned from offering algorithms in other countries. For instance, one of the key objectives for the 2019 UK Kidney Offering Scheme was to avoid prolonged waiting times that are predictable, which is particularly relevant to HSP. In the development of the scheme, different methods of prioritization were considered. These included priority tiers and different points weightings based on factors including sensitization, matchability, and waiting time, and the methods were evaluated by analyzing simulated data across different potential schemes. The 2019 UK scheme is expected to significantly reduce variation in waiting time in sensitized patients, and this reduction is also expected to be seen across other factors, including ethnicity. Although this paper highlights inequities in the ET system and Germany in particular, it highlights the need for all organ allocation algorithms to be reviewed and alternatives extensively modeled to generate algorithms to improve overall equity.