HLA-DQ Mismatching and Kidney Transplant Outcomes

Abstract

Background and objectives: Recent evidence suggests that HLA epitope-mismatching at HLA-DQ loci is associated with the development of anti-DQ donor-specific antibodies and adverse graft outcomes. However, the clinical significance of broad antigen HLA-DQ mismatching for graft outcomes is not well examined.

Design, setting, participants, & measurements: Using the United Network Organ Sharing/the Organ Procurement and Transplantation Network (UNOS/OPTN) data, patients with primary kidney transplants performed between 2005 and 2014 were included. Patients were classified as having either zero HLA-DQ mismatches, or one or two HLA-DQ mismatches. Primary outcomes were death-censored graft survival and incidence of acute rejection.

Results: A total of 93,782 patients were included. Of these, 22,730 (24%) and 71,052 (76%) received zero and one or two HLA-DQ mismatched kidneys, respectively. After adjusting for variables including HLA-ABDR, HLA-DQ mismatching was associated with a higher risk of graft loss in living kidney donor recipients with an adjusted hazard ratio (HR) of 1.18 (95% confidence interval [95% CI], 1.07 to 1.30; P<0.01), but not in deceased kidney donor recipients (HR, 1.05; 95% CI, 0.98 to 1.12; P=0.18) (P value for interaction <0.01). When taking cold ischemic time into account, HLA-DQ mismatching was associated with a higher risk of graft loss in deceased kidney donor recipients with cold ischemic time ≤17 hours (HR, 1.12; 95% CI, 1.02 to 1.27; P=0.002), but not in deceased kidney donor recipients with cold ischemic time >17 hours (HR, 0.97; 95% CI, 0.88 to 1.06; P=0.49) (P value for interaction <0.01). Recipients with one or two HLA-DQ mismatched kidneys had a higher incidence of acute rejection at 1 year, with adjusted odds ratios of 1.13 (95% CI, 1.03 to 1.23; P<0.01) in deceased donor and 1.14 (95% CI, 1.03 to 1.27; P=0.02) in living donor kidney transplant recipients. Specific donor-DQ mismatches seemed to be associated with the risk of acute rejection and graft failure, whereas others did not.

Conclusions: HLA-DQ mismatching is associated with lower graft survival independent of HLA-ABDR in living donor kidney transplants and deceased donor kidney transplants with cold ischemia time ≤17 hours, and a higher 1-year risk of acute rejection in living and deceased donor kidney transplants.

Keywords: Cold Ischemia; Epitopes; Graft Survival; HLA-DQ Antigens; Humans; Incidence; Living Donors; Odds Ratio; Tissue and Organ Procurement; kidney transplantation; transplant outcomes.

Graphical abstract

Figure 1.

Patients who had missing data on HLA-DQ matching, discrepant data between donor's initial HLA-DQ typing and retyping, and patients who had HLA-DQ1 and/or HLA-DQ3 serotypes or patients whose donor kidneys had HLA-DQ1 and/or HLA-DQ3 serotypes were excluded in the patient selection process for the primary outcome analyses. MM, mismatches.

Figure 2.

Patients with HLA-DR mismatches and two HLA-DQ mismatches were excluded to better examine the effect of each HLA-DQ antigen mismatches. These recipients were divided into three cohorts: (1) deceased donor kidney transplant (DDKT) recipients with cold ischemic time of ≤17 hours and living donor kidney transplant (LDKT) recipients, (2) deceased donor kidney transplant recipients with cold ischemic time (CIT) of ≤17 hours only, and (3) living donor kidney transplant recipients only. MM, mismatches.