Intimal arteritis (v-lesions) in kidney transplant biopsies has been believed to have major prognostic and diagnostic significance. We assessed the relationship of v-lesions to prognosis and rejection in 703 indication biopsies from two prospective studies, three days to 35 years post transplant. V-lesions, usually mild (v1), were noted in 49 biopsies (7%) and surprisingly had no impact on survival compared to biopsies with no v-lesions, whether in all biopsies, in ABMR, or in TCMR (Figure 1). Pathologists using current conventions almost always interpreted v-lesions as T cell-mediated rejection (TCMR), either pure or mixed with antibody-mediated rejection (ABMR). We used microarray-based molecular tests as a histology-independent assessment of the relationship of v-lesions to rejection. The molecular scores questioned the conventional diagnoses in 29/49 biopsies (59%): for example, 10 conventional “TCMR” had no molecular rejection, and nine conventional “mixed” had only pure molecular ABMR. We sub-classified v-lesion biopsies into 21 i>1/t>1 v-lesion (“itv”) biopsies and 28 isolated v-lesion biopsies. The extent of inflammation and tubulitis was critical to interpretation of v-lesions. Molecular TCMR scores were positive in 95% of itv biopsies but only 21% of isolated v biopsies. Molecular ABMR scores were often positive in isolated v-lesion biopsies (46%), associated with donor-specific antibody (DSA). Time of biopsy post transplant was important for interpreting isolated v-lesions: early isolated v biopsies often had no molecular rejection and were DSA negative, whereas most after one year had positive DSA and ABMR scores. Thus v-lesions in indication biopsies have no impact on prognosis and can reflect TCMR, ABMR, or no rejection. Time post transplant, DSA, and accompanying tubule-interstitial inflammation provide a probabilistic basis for interpreting v-lesions (Table 1) until molecular tests are available.

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