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The threshold for intimal arteritis (v-lesion) is low, and detection of v1 is sufficient for a diagnosis of TCMR Grade II-III, and in the presence of DSA for a diagnosis of probable AMR. Banff 2024 questions the significance of so-called isolated v-lesions when tubulointerstitial inflammation or microvascular inflammation is absent. Biopsy-based transcript diagnostics might help with clarification.
We analyzed 675 kidney allograft biopsies assessed by histology and biopsy-based transcript diagnostics using the Molecular Microscope Diagnostics System (MMDx) platform from two centers (Zurich and Prague). 133 kidney allograft biopsies with v-lesions (isolated v-lesion, n=32; v-lesion with TCMR/Borderline, n=10; v-lesion with AMR/MVI, n=64; and v-lesion with mixed rejection, n=27) were compared to 542 biopsies without v-lesions (no rejection, n=244; TCMR/Borderline, n=42; AMR/MVI, n=228; and mixed rejection, n=28).
Isolated v-lesions showed molTCMR in 1/32 and molAMR in 1/32 cases, comparable to non-rejection (11/244, p=0.25; 19/244, p=0.94). V-lesions with TCMR/Borderline showed molTCMR in 3/10 (30%), comparable to 13/42 (31%) cases with TCMR/Borderline w/o v-lesions (p=0.34). Interestingly, v-lesions with AMR/MVI showed molTCMR in 9/64 (14%) compared to only 7/228 (3%) cases with AMR/MVI w/o v-lesions (p <0.001). Among 55 cases with mixed rejection, v-lesions significantly increased the median molTCMR score (0.24 (IQR 0.04-0.77) vs 0.06 (IQR 0.01-0.41), p=0.02), with no difference in AMR score (0.37 (IQR 0.08-0.8) vs 0.37 (0.15-0.84), p=0.6). MolAKI categories were consistently higher in biopsies with v-lesions across all groups.
V-lesions are associated with molAKI. With respect to rejection, biopsies with isolated v-lesions are molecularly comparable to non-rejection biopsies, supporting the new Banff 2024 category of “isolated v” instead of TCMR grade II-III. Interestingly, v-lesions appear to be a driver of molTCMR among cases with microvascular inflammation, but not tubulointerstitial inflammation. Biopsy-based transcript diagnostics have the potential to clarify mixed rejection phenotypes in the presence of v-lesions.
