Immunologic clustering of donor-specific antibodies and clinical outcomes in kidney transplant recipients.

BACKGROUND: Donor-specific antibodies (DSA) against human leukocyte antigens (HLA) are associated with increased immunologic risk in kidney transplant recipients (KTR). However, outcomes among DSA-positive patients are highly variable. Traditional markers, such as DSA class and mean fluorescence intensity (MFI), often fail to capture the multidimensional nature of immunologic risk. AIM: This retrospective study aims to stratify DSA-positive KTR into immunologic risk groups using unsupervised machine learning and to assess the relationship between antibody profiles and early post-transplant outcomes. METHODS: During the study period, 260 kidney transplants were performed at King Fahad Armed Forces Hospital in Saudi Arabia, of which 151 recipients were DSA-positive. Clustering analysis was performed in 112 DSA-positive recipients with complete immunologic and follow-up data. Key variables used for clustering included DSA class, number of DSA, cumulative MFI, early graft function (estimated glomerular filtration rate at 4 months), and HLA mismatch. K-means clustering was applied to identify distinct immunologic risk groups. Clinical outcomes, including acute rejection, graft loss, delayed graft function, and mortality, were compared across clusters. RESULTS: Three distinct clusters were identified: High-risk (n = 58) with both Class I and II DSA, high DSA numbers and MFI, and the highest rates of acute rejection (6.9%), graft loss (6.9%), and mortality (5.2%); intermediate-risk (n = 34) with predominantly Class II DSA, moderate MFI, and mild graft loss and mortality; and low-risk (n = 20) with isolated Class I DSA, low DSA numbers and MFI, and excellent early graft function with minimal complications. Clusters demonstrated a clear gradation of immunologic burden, which corresponded with early post-transplant outcomes. Principal component analysis showed clear separation among the three groups. CONCLUSION: Unsupervised clustering effectively stratifies DSA-positive KTR into clinically meaningful risk groups. High-risk recipients with broad and strong DSA profiles are more likely to experience early adverse outcomes. Low-risk recipients have favorable early graft function. This data-driven approach may help guide individualized monitoring, donor selection, and immunosuppression strategies for DSA-positive KTR.