Diffuse C4d staining of peritubular capillaries in renal allograft following bamlanivimab therapy

Neutralizing monoclonal antibodies such as bamlanivimab emerged as promising agents in treating kidney transplant recipients with COVID‐19. However, the impact of bamlanivimab on kidney allograft histology remains unknown. We report a case of a kidney transplant recipient who received bamlanivimab for COVID‐19 with subsequent histologic findings of diffuse peritubular capillary C4d staining. A 33‐year‐old man with end‐stage kidney disease secondary to hypertension who received an ABO compatible kidney from a living donor, presented for his 4‐month protocol visit. He was diagnosed with COVID‐19 44 days prior to his visit and had received bamlanivimab with an uneventful recovery. His 4‐month surveillance biopsy showed diffuse C4d staining of the peritubular capillaries without other features of antibody‐mediated rejection (ABMR). Donor‐specific antibodies were negative on repeat evaluations. ABMR gene expression panel was negative. His creatinine was stable at 1.3 mg/dl, without albuminuria. Given the temporal relationship between bamlanivimab and our observations of diffuse C4d staining of the peritubular capillaries, we hypothesize that bamlanivimab might bind to angiotensin‐converting enzyme 2, resulting in classical complement pathway and C4d deposition. We elected to closely monitor kidney function which has been stable at 6 months after the biopsy. In conclusion, diffuse C4d may present following bamlanivimab administration without any evidence of ABMR. Peritubular C4d staining observed in the kidney allograft of a patient who received Bamlanivimab for COVID‐19 may reflect classical complement pathway activation by the interaction of Bamlanivimab and angiotensin converting enzyme 2.