Enhancing Kidney Transplant Success: Simulation of Prospective Pirche-Ii Molecular Matching in Canada

Organ allocation to minimize Human Leukocyte Antigens (HLA) disparity between donor and recipient has been shown to improve outcomes but is limited by the enormous HLA diversity. PIRCHE-II in silico model considers the HLA peptide binding characteristics of recipients to quantitate molecular compatibility. We have applied a simplified match algorithm in a well characterised nested population-based cohort of ~1500 heterogenous renal patients and donors to develop a basic model to simulate PIRCHE-II optimised kidney allocation within the National Canadian organ transplant program. Simulation models optimising for PIRCHE-II score demonstrate that molecular matching across all 5 HLA gene loci (A, B, C, DR, DQ) is achievable in <10% of patients, and hence is not realistic for clinical allocation. In contrast, molecular matching with a low PIRCHE-II score at the principal HLA class II DRB1 or DQB1 loci may be achieved in over 90% of patients compared with the base-case scenario. In reality, the precise matching probability is governed by multiple factors including waiting-list size, donor frequency, and other allocation restrictions (i.e. ABO blood type, presence of anti-HLA antibodies, clinical urgency), which would further impact match probability. Single-gene PIRCHE-II estimates therefore provide a rapid and realistic instrument for prospective molecular matching and may be combined with real-time nanopore donor sequencing and solid-phase HLA antibody detection at the time of transplant to enable prospective epitope-based allocation.