Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival

Abstract

Background and objectives: Panel reactive antibody informs the likelihood of finding an HLA-compatible donor for transplant candidates, but has historically been associated with acute rejection and allograft survival because testing methods could not exclude the presence of concomitant donor-specific antibodies. Despite new methods to exclude donor-specific antibodies, panel reactive antibody continues to be used to determine the choice of induction and maintenance immunosuppression. The study objective was to determine the clinical relevance of panel reactive antibody in the absence of donor-specific antibodies.

Design, setting, participants, & measurements: Retrospective observational study of kidney allograft survival among 4058 zero HLA-A-, B-, DR-, and DQB1-mismatched transplant recipients without antibodies to donor kidney antigens encoded by these HLA gene loci.

Results: Among 4058 first and repeat transplant recipients, patients with calculated panel reactive antibody (cPRA) 1%-97% were not at higher risk of transplant failure, compared with patients with cPRA of 0% (death censored graft loss: hazard ratio, 1.07; 95% confidence interval, 0.82 to 1.41). Patients with cPRA ≥98% had a higher risk of graft loss from any cause including death (hazard ratio, 1.39; 95% confidence interval, 1.08 to 1.79) and death censored allograft failure (hazard ratio, 1.78; 95% confidence interval, 1.27 to 2.49). In stratified analyses, the higher risk of graft loss among patients with cPRA ≥98% was only observed among repeat, but not first, transplant recipients. In subgroup analysis, there was no association between cPRA and graft loss among living related transplant recipients.

Conclusions: Calculated panel reactive antibody is poorly associated with post-transplant immune reactivity to the allograft in the absence of donor-specific antibody.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_25_CJN13640820_final.mp3.

Keywords: acute rejection; antibodies; risk factors; transplant outcomes.

Graphical abstract

Figure 1.

Assembly of the study cohort. cPRA, calculated panel reactive antibody.

Figure 2.

Unadjusted Kaplan-Meier curves of time to graft loss from any cause including death, death-censored graft loss, and death with a functioning graft, by calculated panel reactive antibody group. Time to graft loss from any cause including (A) death, (B) death-censored graft loss, and (C) death with a functioning graft, by calculated panel reactive antibody (cPRA) group. The number of patients at risk for individual outcomes is provided in Supplemental Table 1.

Figure 3.

Unadjusted Kaplan-Meier curves of time to death-censored graft loss among first transplant recipients and repeat transplant recipients. Time to death-censored graft loss among (A) n=2996 first transplant recipients; (B) n=1062 repeat transplant recipients. The number of patients at risk for individual outcomes is provided in Supplemental Table 2. cPRA, calculated panel reactive antibody.

Figure 4.

Unadjusted Kaplan-Meier curves of subgroup analyses show time to death-censored graft loss among recipients of a living related transplant grouped by cPRA, patients treated with depleting antibody induction, patients treated with nondepleting antibody induction, and patients treated without antibody induction. Subgroup analyses show time to death-censored graft loss among (A) 1250 recipients of a living related transplant grouped by cPRA; (B) 2598 patients treated with depleting antibody induction; (C) 922 patients treated with nondepleting antibody induction; (D) 517 patients treated without antibody induction. The number of patients at risk for individual outcomes is provided in Supplemental Table 3.