Assessing the specificity of the virtual cross-match in kidney transplant patients: A quality improvement initiative in a Canadian institution

Background The virtual crossmatch (VXM) is a novel tool used to identify donor-specific antibodies (DSA) in kidney transplantation without requiring physical donor samples, reducing cold ischemia time (CIT). This study evaluates the specificity of VXM compared to the prospective crossmatch (PXM)/flow cytometric crossmatch (FCXM) in kidney transplant recipients with varying levels of cumulative panel reactive antibodies (cPRA) at a Canadian tertiary care institution. Methods We conducted a retrospective analysis of all VXMs performed at the London Health Sciences Centre, Ontario from 2020 to 2023. Data included patient demographics, cPRA levels, FCXM results, and DSA titers. Patients were categorized by cPRA levels (0–20, 21–40, 41–60, 61–80, and 81–100%), and the Z-test was used to compare the proportion of positive crossmatches across these groups. A p-value of 0.05). However, significantly higher positive PXM rates were observed in the 61–80% and 81–100% groups ( p = 0.0001 and p = 0.00013, respectively). Positive DSA titers were statistically significant only in the cPRA 81–100% group (24%, p = 0.0002). VXM demonstrated high specificity for predicting negative PXM outcomes in cPRA ≤60% but was less predictive for highly sensitized patients (cPRA >60%). Conclusions The VXM reliably predicts negative FCXM outcomes in patients with cPRA ≤60%, supporting its use in this population to streamline workflows and reduce CIT. For cPRA >60%, confirmatory FCXM remains necessary prior to transplantation due to the persistent likelihood of positive crossmatches, likely driven by non-HLA antibodies and allele-specific DSAs. Tailored protocols and technological advancements are essential to optimize crossmatch processes.