NPJ Digit Med. 2026 Jan 10. doi: 10.1038/s41746-025-02323-5. Online ahead of print.
ABSTRACT
We address a critical clinical gap in real-world kidney transplantation (KT), the long-standing disconnect between structured longitudinal follow-up and text-defined clinical rules, which often leads to inconsistent reporting, poor policy compliance, and non-reproducible outcomes across centers. To resolve this, we introduce KT-LLM, a verifiable orchestration layer that bridges sequence modeling with policy and terminology-aware reasoning, tailoring explicitly to KT clinical workflows. KT-LLM ensures clinical decision-making is grounded in authority by constraining knowledge access to Banff kidney allograft pathology references, OPTN, and SRTR policy documents via retrieval-augmented generation. This design anchors answers and computable checklists to versioned sources, enabling full auditability and reducing subjective interpretation errors. The system coordinates three clinically focused, auditable agents: (i) Agent-A (SRTR-MambaSurv): Optimizes discrete-time survival and competing risk prediction from TRF-aligned trajectories via a linear-time inference backbone to personalize follow-up scheduling; (ii) Agent-B (OPTN-BlackClust): identifies clinically distinct population subtypes using stable deep embedded clustering, supporting individualized treatment stratification; (iii) Agent-C (Policy-Ops): encodes OPTN and UNOS submission timelines, SRTR reporting cadence, and Banff terminology into executable rules, returning pass, warn and fail outcomes with versioned evidence to ensure policy compliance. On de-identified OPTN and UNOS cohorts, KT-LLM outperformed strong baselines in evidence attribution and predictive calibration. Critically, it retained the ability to surface clinically distinct subgroups among Black recipients, which aligns with prior reports of outcome heterogeneity, while avoiding overgeneralization of claims beyond the analyzed window. This supports equitable subgroup analysis while avoiding clinical overreach. By anchoring reasoning and outputs to versioned policies and terminology, KT-LLM transforms the model to govern KT workflows into an auditable, clock-synchronized process. This offers a practical solution to enhance reproducibility, monitor fairness across centers and eras, and standardize clinical practice, addressing unmet needs for scalable, reliable KT care in real-world settings.
PMID:41520040 | DOI:10.1038/s41746-025-02323-5