Clinical significance of the distribution of C4d deposits in different anatomic compartments of the allograft kidney

Ibrahim Batal, Alin Girnita, Adriana Zeevi, Bassel Abou Saab, Sean Stockhausen, Ron Shapiro, Amit Basu, Henkie Tan, Claire Morgan, Parmjeet Randhawa
Modern Pathology 2008, 21 (12): 1490-8
Diffuse C4d deposition in peritubular capillaries is a well-recognized marker of antibody-mediated rejection. The significance of staining patterns that are focal or affect non-peritubular capillary compartments is less well defined. Paired frozen section and paraffin-embedded tissue stains were performed in 52 kidney allograft biopsies, and correlated with clinicopathologic parameters. Diffuse peritubular capillary C4d deposits were more often seen in frozen sections (22/52, 43% frozen tissue vs 10/52, 19% paraffin-embedded tissue), whereas focal staining was observed more frequently within paraffin sections (13/52, 25% paraffin-embedded tissue vs 7/52, 14% frozen tissue). In biopsies taken from patients with a history of donor-specific antibodies, diffuse, focal and negative peritubular capillary C4d staining patterns were seen in 11/14 (79%), 1/14 (7%) and 2/14 (14%) of frozen biopsies vs 5/14 (36%), 6/14 (43%) and 3/14 (21%) of paraffin-embedded biopsies. Transplant glomerulopathy score in paraffin-embedded biopsies was higher in specimens with vs without glomerular basement membrane C4d staining (1.5+/-0.8 vs 1.0+/-0.6, P=0.03). Tubular basement membrane staining was present in 4% paraffin-embedded and 48% frozen specimens independent of tubular atrophy. Arteriolar hyalinosis score in paraffin-embedded specimens was higher in biopsies with vs those without arteriolar C4d deposits (1.3+/-0.9 vs 0.9+/-0.8, P=0.04). Arterial staining was unrelated to the degree of intimal thickening. In conclusion, peritubular capillary deposits correlate well with circulating donor-specific antibody. For paraffin-embedded tissue, combining the results of focal and diffuse staining allows a diagnostic sensitivity comparable to diffuse staining in frozen tissue. Finally, C4d deposits preferentially in lesions of chronic transplant glomerulopathy and arteriolar hyalinosis.

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