Transplanting the Elderly: Mandatory Age- and Minimal Histocompatibility Matching

Abstract

Worldwide over 40% of patients receiving renal replacement therapy (RRT) are aged 65 years or older, a number that is still increasing. Renal transplantation is the preferred RRT, providing substantial survival benefit over those remaining on dialysis, including the elderly. Only 3% of patients aged 65 years or older accepted on the waiting list actually received a kidney transplant offer within the Eurotransplant allocation region. To increase the chance for elderly to receive a timely kidney transplant, the Eurotransplant Senior Program was introduced. The ESP supports local allocation of older kidneys to older donors in order to decrease cold ischemia time, while disregarding former exchange principles based on matching for HLA antigens. As a consequence, more elderly received a kidney transplant and a relative higher incidence of acute rejection resulted in additional courses of high steroids and/or depleting antibody therapy. Since death with a functioning graft due to infections is the dominant reason of graft loss in elderly, more intense clinical immunosuppression to prevent or treat acute rejection is not a very attractive option. Therefore in elderly kidney transplant candidates, we advocate reintroduction of minimal histocompatibility criteria (i.e., HLA-DR matching) followed by age-matching with mandatory local/regional allocation to also facilitate short cold ischemia.

Impact of HLA compatibility in recipients of kidneys from expanded criteria donors: A Collaborative Transplant Study Report

“…A high degree of HLA incompatibility between donor and recipient has been shown to predispose to development of de novo donor‐specific HLA antibodies (DSAs) as well as to reactivation of preformed DSAs (Dreyer & de Fijter, 2020; Foroutan et al., 2019; Mohan et al., 2012). This may lead to antibody‐mediated rejection and subsequently impair long‐term allograft survival (Mehra & Baranwal, 2016; Slavcev, 2013).…”

“…Therefore, it has been proposed that a minimal degree of HLA matching (e.g. for HLA‐DR) should be introduced also for the Eurotransplant Senior Program in order to reduce the incidence of rejection episodes and thus the need for more intense immunosuppression, thereby diminishing excess mortality due to infection (Dreyer & de Fijter, 2020; de Fijter, 2009). This strategy could potentially represent a compromise between short waiting times, short cold ischaemia time and reduced risk of rejection.…”

Hypoproliferative human NPC xenografts survived extendedly in the brain of immunocompetent rats

“…The immunostaining results showed that HLA-ABC expression remained barely detectable in all non-rejecting brains at any time point up to 12 wpt (Fig.S5C), and very few HLA-ABC positive cells could be occasionally identi ed if given much prolonged survival time(data from another experiment with immune-suppression). We also failed to detect HLA-DR expression ( Fig.S5C), which has long been strongly associated to transplant rejection 31 . Thus, the expressions of HLA-ABC and HLA-DR antigens retained a low level in vivo during our observation time window, and should not be responsible for initiation of the late-onset human cell rejection.…”

Should We Perform Old-For-Old Kidney Transplantation during the COVID-19 Pandemic? The Risk for Post-Operative Intensive Stay

“…Indeed, after transplantation, he had to be admitted to the ICU on postoperative day seven due to urosepsis and suspected cardiac infarction. Infectious complications are common among old kidney recipients and have been shown to be their second most frequent cause for DWFG [ 16 ]. In our cohort, 3 out of 17 (17.6%) patients had to be admitted to the ICU because of sepsis.…”

“…The Eurotransplant Senior Program (ESP) is a special kidney transplant program which was initiated in 1999 to reduce waiting times by allocating kidneys from deceased donors aged ≥65 years to old recipients aged ≥65 years. Before that date, only 3% of patients aged 65 years or older actually received a KT offer within the Eurotransplant region, because younger patients with more favorable outcomes were prioritized [ 16 ]. In ESP, organ allocation is not based on immunological compatibility, but on local, regional or national allocation and AB0-compatibility, in order to reduce cold ischemia time (CIT).…”