Association Between Donor-Recipient Biological Relationship and Allograft Outcomes After Living Donor Kidney Transplant

Abstract

IMPORTANCE The proportion of living donor kidney transplants from donors unrelated to their recipients is increasing in the US. OBJECTIVE To examine the association between donor-recipient biological relationship and allograft survival after living donor kidney transplant. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used Organ Procurement and Transplantation Network data on US adult living donor kidney transplants (n = 86 154) performed from January 1, 2000, to December 31, 2014, excluding cases in which recipients previously received a kidney transplant (n = 10 342) or key data were missing (n = 2832). Last follow-up was March 20, 2020. EXPOSURES Donor-recipient biological relationship. MAIN OUTCOMES AND MEASURESThe primary outcome was death-censored allograft failure.Univariate and multivariable time-to-event analyses were performed for death-censored allograft failure for the overall cohort, then separately for recipients with and without primary diagnoses of cystic kidney disease and for transplants from African American and non-African American donors. RESULTSAmong the 72 980 transplant donor and recipients included in the study (median donor age, 41 years; interquartile range [IQR], 32-50 years; 43 990 [60%] female; 50 014 [69%] White), 43 174 (59%) donors and recipients were biologically related and 29 806 (41%) were unrelated. Donors related to their recipients were younger (median [IQR] age, 39 [31-48] vs 44 [35-52] years) and less likely to be female (24 848 [58%] vs 19 142 [64%]) or White (26 933 [62%] vs 23 081 [77%]). Recipients related to their donors were younger (median [IQR] age, 48 [34-58] vs 50 [40-58] years), more likely to be female (18 035 [42%] vs 10 530 [35%]), and less likely to have cystic kidney disease (2530 [6%] vs 4600 [15%]). Related pairs had fewer HLA mismatches overall). After adjustment for HLA mismatches, donor and recipient characteristics, and transplant era, donor-recipient biological relationship was associated with higher death-censored allograft failure (hazard ratio, 1.05; 95% CI, 1.01-1.10; P = .03). When stratified by primary disease, this association persisted only for recipients without cystic kidney disease. When stratified by donor race, this association persisted only for transplants from African American donors. CONCLUSIONS AND RELEVANCEIn this cohort study, living donor kidney transplants from donors biologically related to their recipients had higher rates of allograft failure than transplants from donors unrelated to their recipients after HLA matching was accounted for. Further study is needed to determine which genetic or socioenvironmental factors are associated with this finding.

How good is a living donor? Systematic review and meta-analysis of the effect of donor demographics on post kidney transplant outcomes

“…Finally, concerning the genetic relationship with the recipient, graft function and survival were favored by the biological link between donor and recipient, possibly in relation of better histocompatibility [ 59 ], that also reduces the incidence of acute rejection, as previously discussed. Given that some transplant candidates may have multiple potential donors to choose from, a better understanding of the association between donor-recipient biological relationship and post-transplant outcomes can improve donor selection.…”

Strategies to Overcome HLA Sensitization and Improve Access to Retransplantation after Kidney Graft Loss

“…The advantage of living donation in retransplantation, is even more valuable for the sensitized patients: organ-shortage problem is overcome, and it is easier to cross the HLA barrier challenges. Genetically related donors have better HLA matches [ 90 ], ischemia-reperfusion injury tends to be lower which decreases the exposure to HLA antigens [ 91 ], IS after first graft loss can be maintained in higher doses [ 31 ] and desensitization protocols are more effective [ 92 ]. Living donation also allows kidney-paired donation for AB0 or HLA incompatible pairs, with similar outcomes to direct living donation [ 93 , 94 ].…”

To Understand the Disparities in Living Kidney Transplantation Outcomes, Look to the Community

“…Thus, temporal factors, such as improvements in transplantation surgery and posttransplantation care, were not the primary reasons for the observed differences.What could be responsible for these surprising findings? The clues may be found in Table 3 of the study by Husain et al 3 When the donor was African American, the hazard ratio of allograft failure was 1.12 (95% CI, 1.01-1.23), but when the donor was not African American, the hazard ratio was no longer significant (hazard ratio, 1.03; 95% CI, 0.98-1.08). These added findings suggest that additional factors common to African American donors beyond what was measured were negatively associated with allograft survival.In the absence of reliable patient-level measures of socioeconomic position and other factors that may affect patient outcomes, investigators often use area-based measures.…”

“…What could be responsible for these surprising findings? The clues may be found in Table 3 of the study by Husain et al 3 When the donor was African American, the hazard ratio of allograft failure was 1.12 (95% CI, 1.01-1.23), but when the donor was not African American, the hazard ratio was no longer significant (hazard ratio, 1.03; 95% CI, 0.98-1.08). These added findings suggest that additional factors common to African American donors beyond what was measured were negatively associated with allograft survival.…”

“…Because the first living successful kidney transplant to remain functional for several years was performed in 1954 between identical twins, it has been assumed that relatedness between donors and recipients leads to superior outcomes. Husain et al challenge that assumption.…”