title: The significance of renal C4d staining in patients with BK viruria, viremia, and nephropathy.
abstract: Peritubular capillary C4d staining in allograft kidney is an important criterion for antibody-mediated rejection. Whether BK virus infection can result in complement activation is not known. We studied 113 renal allograft biopsies from 52 recipients with a history of BK virus activation. The samples were classified into four groups according to the concurrent detection of BK virus DNA in urine, plasma, and/or biopsy: BK-negative (n=37), viruria (n=53), viremia (n=7), and nephropathy (n=16) groups. The histological semiquantitative peritubular capillary C4d scores in the viremia (0.3+/-0.8) and BK nephropathy (0.6+/-0.9) groups were lower than those in the BK-negative group (1.2+/-1.1, P=0.05 and P=0.06, respectively) and the viruria group (1.2+/-1.1, P=0.04 and P=0.06, respectively). Diffuse or focal peritubular capillary C4d staining was present in 9/76 (12%) and 14/76 (19%) of all samples with concurrent BK virus reactivation (viruria, viremia, and nephropathy). The diagnosis of antibody-mediated rejection could be established in 7/9 (78%) and 5/14 (36%) of these samples, respectively. Diffuse tubular basement membrane C4d staining was restricted to BK nephropathy cases (4/16, 25%). Semiquantitative tubular basement membrane C4d scores were higher in BK nephropathy (1.2+/-1.3) compared with BK-negative (0.05+/-0.3, P=0.017) and viruria (0.0+/-0.0, P=0.008) groups. Bowman's capsule C4d staining was more frequent in BK nephropathy (5/16) compared with the aforementioned groups (2/36 (P=0.023) and 4/51 (P=0.03), respectively). Within the BK nephropathy group, samples with tubular basement membrane stain had more infected tubular epithelial cells (12.1+/-7.6% vs 4.4+/-5.0%, P=0.03) and a trend toward higher interstitial inflammation scores. In conclusion, peritubular capillary C4d staining remains a valid marker for the diagnosis of antibody-mediated rejection in the presence of concurrent BK virus infection. A subset of biopsies with BK nephropathy shows tubular basement membrane C4d staining, which correlates with marked viral cytopathic effect.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. batali2@upmc.edu
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Batal
authors.forename: Hanady
authors.initials: H
authors.lastname: Zainah
authors.forename: Sean
authors.initials: S
authors.lastname: Stockhausen
authors.forename: Amit
authors.initials: A
authors.lastname: Basu
authors.forename: Henkie
authors.initials: H
authors.lastname: Tan
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: Alin
authors.initials: A
authors.lastname: Girnita
authors.forename: Parmjeet
authors.initials: P
authors.lastname: Randhawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001739:BK Virus / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002648:Child; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D027601:Polyomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014412:Tumor Virus Infections / Q000378:metabolism* / Q000473:pathology; D014766:Viremia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014775:Virus Activation
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d