Background: Detection of peritubular capillary (PTC) complement C4d on renal allograft biopsy is a histologic marker (along with serum anti-donor antibody, PTC inflammatory cells and renal dysfunction) to diagnose antibody-mediated renal allograft rejection (AMR). Validity of PTC C4d detection has often been restricted to cortical (C) staining for diagnosis, whereas medullary (M) samples considered limited in value. Hence, repeated biopsy is often considered to obtain this diagnosis if the biopsy contains little or no renal cortex. Risk of biopsy complications such as bleeding increases with each needle pass, so efficient biopsy management is important to reduce risk. However, adequate sampling is also important for diagnostic accuracy.

The purpose of this study was to determine the reliability of C vs. M C4d staining in kidney allograft biopsies for the diagnosis of antibody-mediated rejection. Methods: Retrospectively, 11 kidney allograft biopsies (that contained both C and M in one core) from patients with confirmed AMR were dual-stained for C4d (green) and CD31 (red-endothelial cell marker). Each sample was assessed for CD31 and dual (orange) C4d and CD31 staining in at least 10 random fields at 400x magnification. The percentage of double C4d/CD31 PTC (or vasa recta in M) out of CD31-positive vessels was calculated separately for C and M in the same sample. Two-tailed Student t-test was used for comparison between C and M in the samples assessed. Results: (See Figure 1 A & B): Mean and standard deviation for C was 0.79 %+/- 0.10, and for M was 0.84% +/- 0.07. Paired T-test comparison of means showed no significant difference (p = 0.17) between C4d staining in cortex and medulla from the same renal allograft cores.

Conclusion: Our data indicate that C4d staining is similar in capillaries of C and M. While renal allograft cortex is desirable for overall diagnostic purpose in kidney allograft biopsies, samples containing predominantly or exclusively medulla may be sufficient for C4d analysis in attaining the diagnosis of AMR.

CITATION INFORMATION: Von Visger J., Von Visger C., Satoskar A., Nadasdy T., Hemminger J., Brodsky S. Diagnostic Usefulness of Medullary C4d Staining in Renal Allografts Am J Transplant. 2017;17 (suppl 3).

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