Molecular Classification Predicts Clinical Outcomes of Kidney Transplant Recipients With Microvascular Inflammation, Donor-specific Antibodies-negative and C4d-negative.

BACKGROUND

Microvascular inflammation (MVI), donor-specific antibodies (DSAs)-negative and C4d-negative, was recently defined as a distinct phenotype by Banff 2022 and has been associated with adverse clinical outcomes. We have developed a model for rejection-related molecular classification of renal allograft biopsies using gene expression profiling of formalin-fixed paraffin-embedded renal biopsy tissue and evaluated its performance in patients with MVI.

METHODS

Using this updated gene expression profiling-based multiclass model, we evaluated 138 biopsy specimens obtained from a large US transplant center, which included 42 biopsies diagnosed as MVI, DSA-negative, and C4d-negative. Clinical outcomes of patients in this MVI biopsy group were analyzed in relation to their molecular classifications.

RESULTS

The molecular rejection classifications exhibited robust concordance with histology diagnoses of no rejection, antibody-mediated rejection, and T-cell-mediated rejection in this independent cohort, with concordance rates varying in each group from 85% to 93%. The molecular classification also showed a significant association with differential renal function and graft survival in the MVI, DSA-negative, and C4d-negative group.

CONCLUSIONS

Our model demonstrates significant molecular differentiation among antibody-mediated rejection, T-cell-mediated rejection, and no rejection. In addition, our model classified MVI, DSA-negative, and C4d-negative samples into molecular subgroups associated with divergent clinical outcomes.