Tubular Basement Membrane Deposits of C4d in Biopsies with BK Virus (BKV) Nephropathy (BKN)
I Batal, H Zainah, S Stockhausen, A Basu, H Tan, R Shapiro, P Randhawa. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: BKN has recently been associated with immune complex deposits in the tubular basement membranes (TBM). This study evaluated the deposition of complement degradation product C4d as a potential marker for this phenomenon and investigated if BKV activation can per se lead to C4d deposition in peritubular capillaries (PTC).
Design: We retrospectively examined 113 renal allograft biopsies from 52 kidney transplant recipients with a history of BKV activation defined as an episode of BK viruria (VU). All biopsies had either BKN, or had been performed within 14 days of paired urine and plasma PCR for BKV DNA. The biopsy samples were classified into 4 groups: BKV negative (NEG) (n=37), VU (n=53), viremia (VM) (n=7), and BKN (n=16). Immunohistochemistry for polyclonal C4d (ALPCO Diagnostics, Windham, NH) was performed on formalin fixed paraffin embedded biopsies. PTC and TBM C4d deposits were semi-quantitatively graded (0-3) corresponding to negative, minimal, focal, and diffuse staining, respectively. Bowman's capsule (BC) deposits were recorded as present or absent.
Results: Diffuse PTC staining was observed only in NEG and VU samples [4/37(11%) and 9/53(17%)], while focal staining was observed in all groups [13/37(35%) NEG, 9/53(17%) VU, 1/7(14%) VM, and 4/16(25%) BKN]. PTC C4d scores in VM (0.29 +/-0.76) and BKN (0.56 +/-0.89) groups were significantly lower than the VU group (1.15 +/-1.09, p=0.035 vs. VM, p=0.046 vs. BKN) and tended to be lower than the NEG group (1.19 +/-0.8, p=0.052 vs. VM and p=0.064 vs. BKN). TBM staining was a rare phenomenon that was, in its diffuse form, limited to BKN group 4/16 (25%). Focal TBM staining was observed in 2/16 (12.5%) BKN and 1/37(3%) NEG cases. TBM C4d scores were significantly higher in the BKN group (1.2 +/-1.32) compared to both NEG (0.054 +/-0.33, p=0.017), and VU (0.0 +/-0.0, p=0.008) groups. Similarly, a higher proportion of BC staining was observed in BKN samples (5/16) compared to both NEG (2/36, p=0.023) and VU (4/51, p=0.03) groups. Within BKN samples, biopsies with TBM deposits had higher percentages of infected tubular epithelial cells (12.1 +/-7.6 vs. 4.4 +/-5.0, p=0.03) and a trend toward higher Banff interstitial inflammation scores (2.7+/-0.5 vs. 2.11+/-0.6, p=0.09) compared with BKN biopsies with no TBM deposits.
Conclusions: A subset of biopsies with BKN is associated with C4d deposits in TBM but not PTC. Biopsies with TBM C4d have more pronounced viral cytopathic effect than those without demonstrable C4d.
Monday, March 9, 2009 1:00 PM
Poster Session II # 198, Monday Afternoon