Introduction: Although limiting the number of HLA mismatches between donor and recipient effectively reduces the risk of kidney allograft rejection, this approach has some limitations.   Several algorithms have been developed, aiming to predict alloimmune reactivity. HLA matchmaker (HLA-EPMM) and PIRCHE-II (Predicted Indirectly Recognizable HLA Epitopes) algorithms are promising solutions to estimate the risk for alloreactivity after kidney transplantation.
Method: Retrospective, single-center study, 200 kidney transplant recipients were examined from June 2001 to April 2023. “High Total Eplet MM (≥17) and High All Abv Eplet MM(≥ 7)” and “High PIRCHE-II (≥70) were defined, respectively.“A nadir Tacrolimus concentration” was defined as the lowest FK trough levels < 6ng/ml were collected at least once during the past 12 months.“High intrapatient variability (IPV) of tacrolimus” was also defined as ≥13%.
The primary purpose of our study was to verify whether a combination of HLA-EPMM and PIRCHE-II algorithm can improve risk stratification of kidney transplantation. The 2nd purpose was to evaluate whether high nadir of Tacrolimus concentration (<6ng/ml) and high Intrapatient variability (>13%) are associated with graft failure regarding patients with high-HLA-EP MM (≥17), or high-PIRCHE-II (≥70).
Result: Either high-HLA-EP MM (≥17), or high-PIRCHE-II (≥70) cut-offs did not predict the risk of graft failure. Given that each high-IPV (>13%) or high- -nadir of tacrolimus concentration (<6ng/ml) combined with high-PIRCHE-II or high-HLA total EP MM had an influence on graft outcome, all of every combination of the high/high group had a significantly higher risk of allograft failure than that of the low/low group respectively. High- PIRCHE and high-Total EP MM group had significantly the lowest death censored-graft survival rate compared with high-/low-, low-/high-, and low-/low- groups, respectively.
Conclusion: Either PIRCH-II or HLA-Total EP MM alone was not enough to predict the risk of graft failure. Our study demonstrated that high- PIRCHE / high-EP MM group had the worst graft outcome. Both combination of PIRCHE II and HLA EP MM can stratify the risk of graft failure. Given that each high-IPV or high-nadir of tacrolimus concentration combined with high-PIRCHE-II or high-HLA total EP MM influenced poor graft outcome, our study suggested that patients with high-HLA-EP MM or high-PIRCHE-II require careful monitoring of IPV and a nadir of tacrolimus concentration. Together with HLA EP MM, The PIRCHE-II algorithm can provide a better estimated alloreactive risk for individual patients and eventually an improved allograft kidney survival.