title: Platelet CD61 expression in vascular calcineurin inhibitor toxicity of renal allografts.
abstract: Calcineurin inhibitor (CI) toxicity in renal allografts is frequently associated with arteriolar injury. Platelet activation occurs in response to vascular injury associated with CI therapy. Platelets are detectable in tissue sections by immunohistochemistry for CD61. This immunohistochemical study examines patterns of platelet deposition in CI-associated vascular toxicity of renal allografts. Renal allograft biopsies were grouped into (i) CI-associated thrombotic microangiopathy (CITMA, n = 28); (ii) vascular CI toxicity without thrombotic microangiopathy (VTox, n = 43); and (iii) allograft controls with minimal arteriolopathy abnormalities, both with CI exposure (MA, n = 10) and without CI exposure (NCI, n = 15). Two-micrometer paraffin sections were stained using a monoclonal antibody to CD61 by standard immunoperoxidase methods. Mural and luminal CD61 deposits in arterioles were graded from 0 to 3+, and proportions of arteriolar and glomerular profiles with CD61 deposits were determined for each biopsy. Granular CD61 deposits were detected in arterioles in biopsies with CITMA (92.9%) and VTox (81%) and less frequently in MA (30%) and NCI (33%). The proportion of arterioles with CD61 deposits was greater in CITMA than in VTox (46.3% +/- 28.5% vs 21.3% +/- 22.2%, P = .001) and more extensive than in controls (MA, 3.6% +/- 8.9%; NCI, 3.2% +/- 5.5%). Median arteriolar CD61 grades for CITMA exceeded grades for VTox (2 vs 0.5, P = .001), and CD61 grades in VTox were significantly greater than in controls with MA (0) and NCI (0) (P = .0001). In conclusion, arteriolar mural platelet CD61 deposition was observed in vascular CI toxicity and was most extensive and severe in CI-associated thrombotic microangiopathy. Identification of "insudative platelet arteriolopathy" in renal allograft biopsies, by immunohistochemical detection of CD61, may facilitate recognition of vascular CI toxicity.
authors.affiliation: Department of Pathology, Renal Pathology Laboratory, University of Chicago, Chicago, IL 60637, USA. shane.meehan@uchospitals.edu
authors.forename: Shane M
authors.initials: SM
authors.lastname: Meehan
authors.forename: Rajendra
authors.initials: R
authors.lastname: Baliga
authors.forename: Rajiv
authors.initials: R
authors.lastname: Poduval
authors.forename: Anthony
authors.initials: A
authors.lastname: Chang
authors.forename: Pradeep V
authors.initials: PV
authors.lastname: Kadambi
mesh_terms: D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001792:Blood Platelets / Q000737:chemistry*; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D039661:Integrin beta3 / Q000032:analysis*; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D015539:Platelet Activation; D010974:Platelet Aggregation
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; C061248:ITGB3 protein, human; D007166:Immunosuppressive Agents; D039661:Integrin beta3