The significance of renal C4d staining in patients with BK viruria, viremia, and nephropathy

Ibrahim Batal, Hanady Zainah, Sean Stockhausen, Amit Basu, Henkie Tan, Ron Shapiro, Adriana Zeevi, Alin Girnita, Parmjeet Randhawa

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20 Scopus citations


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 (n37), viruria (n53), viremia (n7), and nephropathy (n16) groups. The histological semiquantitative peritubular capillary C4d scores in the viremia (0.30.8) and BK nephropathy (0.60.9) groups were lower than those in the BK-negative group (1.21.1, P0.05 and P0.06, respectively) and the viruria group (1.21.1, P0.04 and P0.06, 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 (1.21.3) compared with BK-negative (0.050.3, P0.017) and viruria (0.00.0, P0.008) groups. Bowman's capsule C4d staining was more frequent in BK nephropathy (5/16) compared with the aforementioned groups (2/36 (P0.023) and 4/51 (P0.03), respectively). Within the BK nephropathy group, samples with tubular basement membrane stain had more infected tubular epithelial cells (12.17.6% vs 4.45.0%, P0.03) 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.

Original languageEnglish
Pages (from-to)1468-1476
Number of pages9
JournalModern Pathology
Issue number11
StatePublished - Nov 2009
Externally publishedYes


  • BK virus
  • BK virus nephropathy
  • C4d immunostain
  • Viremia
  • Viruria


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