Reassessing the Significance of Intimal Arteritis in Kidney Transplant Biopsy Specimens.
Intimal arteritis (the presence of v-lesions) in kidney transplant biopsy specimens is believed to have major prognostic and diagnostic significance. We assessed the relationship of v-lesions to prognosis in 703 indication biopsy specimens and used microarray-based molecular tests to re-examine the relationship of v-lesions to rejection. v-Lesions were noted in 49 specimens (7%) and were usually mild (v1). The presence of v-lesions had no effect on graft survival compared with the absence of v-lesions. Pathologists using current conventions almost always interpreted v-lesions as reflecting T cell-mediated rejection (TCMR), either pure or mixed with antibody-mediated rejection (ABMR). The molecular scores questioned the conventional diagnoses in 29 of 49 specimens (59%), including ten that were conventional TCMR with no molecular rejection and nine that were conventional TCMR mixed with pure ABMR molecularly. The presence of tubulointerstitial inflammation (i-t) meeting TCMR criteria allowed subclassification of v-lesion specimens into 21 i-t-v-lesion specimens and 28 isolated v-lesion specimens. Molecular TCMR scores were positive in 95% of i-t-v-lesion specimens but only 21% of isolated v-lesion specimens. Molecular ABMR scores were often positive in isolated v-lesion biopsies (46%). Time of biopsy after transplantation was critical for understanding isolated v-lesions: most early isolated v-lesion specimens had no molecular rejection and were DSA negative, whereas most isolated >1 year after transplantation had positive DSA and ABMR scores. Therefore, v-lesions in indication biopsy specimens do not affect prognosis and can reflect TCMR, ABMR, or no rejection. Time after transplantation, DSA, and accompanying inflammation provide probabilistic basis for interpreting v-lesions.
Alberta Transplant Applied Genomics Center, Edmonton, Alberta, Canada; Department of Medicine, Viedma Hospital, Cochabamba, Bolivia; Caja National Health Hospital, Cochabamba, Bolivia; and.
Israel D R
ID
Salazar
Alberta Transplant Applied Genomics Center, Edmonton, Alberta, Canada;
Maribel
M
Merino López
Alberta Transplant Applied Genomics Center, Edmonton, Alberta, Canada;
Jessica
J
Chang
Alberta Transplant Applied Genomics Center, Edmonton, Alberta, Canada; Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada phallora@ualberta.ca.
Philip F
PF
Halloran
D000906:Antibodies / Q000276:immunology*; D001167:Arteritis / Q000276:immunology / Q000473:pathology*; D001706:Biopsy; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*
D000906:Antibodies; D006680:HLA Antigens
kidney; kidney biopsy; kidney transplantation