Claims-Based Phenotyping of Acute Kidney Transplant Rejection in a National Medicare Cohort.

INTRODUCTION

National transplant registries record acute rejection (AR) without the granularity needed to study rejection heterogeneity and prognosis at scale. Whether AR can be stratified by type and severity in national claims data using a claims-based algorithm, and whether these phenotypes correlate with graft outcomes, remains unclear.

METHODS

We conducted a cohort study using the US Renal Data System (USRDS) data including adult kidney transplant recipients from 2012-2021. AR within 12 months posttransplant was identified using International Classification of Diseases codes for transplant complications with evidence of antirejection treatment within 2 weeks. Episodes were categorized by type and severity based on treatment regimen. Biopsy-associated AR was defined by renal biopsy within 14 days before the treatment. Death-censored graft survival was assessed using Kaplan-Meier methods and multivariable Cox proportional hazards models.

RESULTS

Among 92,845 recipients, 5712 AR episodes were identified (69.4% mild acute-cellular rejection [ACR], 8.8% severe ACR, 19.7% antibody-mediated rejection [AMR], and 2.1% mixed [ACR + AMR]). Among 3052 biopsy-confirmed episodes, 3-year death-censored graft survival differed meaningfully across phenotypes (87.9% mild ACR, 80.7% severe ACR, 73.5% AMR, and 68.4% mixed [ACR + AMR] [P < 0.05]), with trends persisting after adjustment for recipient and donor characteristics.

CONCLUSION

Claims-based phenotyping can identify clinically meaningful AR subtypes and prognostic gradients at national scale, enabling more granular national rejection surveillance.