*Purpose: With the new allocation rules implemented in 2014, the number of transplants from A₂ and A₂B donors to B or O recipients (minor ABO incompatibility) has increased significantly, but treatment decisions are often based on data from classical ABO incompatible transplants. In particular the presence of c4d, seen diffusely in virtually all classical ABO incompatible transplants, was assumed to be similarly universal in minor ABO incompatible transplants and thus of little consequence. We sought to review our experience with minor ABO incompatible transplants and characterize our biopsy findings.

*Methods: From a single center’s transplant record from 12/14/2014 to 10/31/2018 all blood group B or O patients who received a blood group A₂ or A₂B kidney were identified. Additional demographic and clinical data was extracted from the medical records of these patients. Finalized pathology reports from renal biopsies were collected and scored by Banff criteria.

*Results: Over the 47-month period since the implementation of KAS we have performed a total of 30 minor ABO incompatible kidney transplants (27 A₂/A₂B to B, 3 A₂ to O). A total of 37 renal biopsies were performed on 18 patients with 13 having multiple biopsies. Biopsies were characterized as either for-cause (n=20) or by protocol (n=17). C4d positivity was found in only 7 biopsies (19%) performed on 5 different patients. C4d positive biopsies were found earlier in the post-transplant course (57 + 41.2 vs. 192 + 165 days, p=0.04). Of the 13 patients with multiple biopsies, c4d was never seen to increase over time even in the setting of clinical deterioration. 3 patients with c4d had follow-up biopsies; in all cases c4d consistently declined over time without clinical intervention. C4d was rarely seen in the absence of clinical indications for biopsy (6/20 for-cause biopsies vs. 1/17 protocol biopsies, p= 0.06). It was not correlated to clinical disease as serum creatinine and P/C ratios did not differ significantly between C4d and non-C4d groups (serum Cr 2.15 + 0.92 vs. 1.84 + 0.78, p=0.37, P/C ratio 0.24 + 0.20 vs. 0.71 + 1.11, p=0.31).

*Conclusions: Overall we found c4d in minor ABO incompatible transplants was clinically insignificant and often an isolated finding on biopsy. Nevertheless, in contrast to classical ABO incompatibility, we found c4d only in a subset of cases in a pattern suggesting early expression which faded over time and without treatment. Further studies should be done to refine our understanding of what causes it to appear in only select cases.

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