Immunosuppression Efficacy via Nonlinear Modeling and Probabilistic Analysis of Human Leukocyte Antigen Match and Dose Effects on Allograft Rejection Risk

Background Human Leukocyte Antigen (HLA) compatibility is a key driver of kidney allograft outcomes, yet how matching interacts with immunosuppressant dosing remains unclear. This study evaluates whether low‐resolution HLA match fractions affect mean dosing and quantified the joint impact of match quality and dose on rejection risk. Methods In 519 transplants grouped by HLA match (0–1.0 in 7 strata), full data completeness and variance homogeneity is confirmed, followed by the usage of one‐way ANOVA to compare mean doses. Ridge‐penalized logistic regression models was fitted at each match level to predict rejection probability across low‐ and high‐dose regimens, deriving absolute and relative risk reductions. Results ANOVA showed no significant dosing differences by match ( F 6,512 = 0.93, p = 0.47). Logistic models revealed that Absolute Risk Reduction rose from ~0.75% at zero match to ~1.25% at perfect match, while mid‐range match groups (0.2–0.6) yielded the highest total prevented rejections under high‐dose therapy. Conclusion Uniform baseline dosing eliminates bias, allowing clear attribution of benefit to immunologic compatibility. These findings endorse a risk‐tailored immunosuppression approach intensifying doses where match is low and potentially reducing them in highly compatible transplants and identify match ranges that maximize rejection prevention.