Unexpected Legacy: Donor-Derived Alport Syndrome and Subclinical Antibody-Mediated Rejection in a Kidney Transplant Recipient with FSGS

Introduction: Alport syndrome is a hereditary glomerulopathy caused by mutations in type IV collagen, characterized by abnormalities in the glomerular basement membrane (GBM). It is rare to identify donor-derived Alport syndrome in kidney transplants. Concurrent antibody-mediated rejection (AMR) can further threaten allograft survival. We present a unique case of donor-derived Alport syndrome identified on surveillance biopsy in a stable kidney transplant recipient. Case Description: A 27-year-old woman with ESKD due to FSGS received a pediatric en bloc deceased donor kidney transplant in June 2021. Baseline creatinine was 0.8 mg/dL. In April 2025, she developed Class II donor-specific antibodies (DQ2, MFI 21,000) amidst prednisone non-adherence. Creatinine remained stable at 0.92 mg/dL with improved proteinuria (0.16 from 0.28). Surveillance biopsy was performed. The biopsy showed 35 glomeruli, four globally sclerosed, with ~10% interstitial fibrosis and tubular atrophy. Light microscopy revealed segmental mild glomerulitis (g1), focal moderate peritubular capillaritis (ptc2) in ~20% of capillaries, and C4d positivity in ~30%—consistent with active AMR. Two glomeruli showed nonspecific segmental sclerosis, without foot process effacement on electron microscopy (EM), ruling out recurrent FSGS. EM showed segmental thickening and lamellation of the GBM with focal basket-weave appearance—hallmark features of Alport syndrome. No immune complex deposits were seen on EM or immunofluorescence. These findings indicate donor-derived Alport syndrome, given the pediatric donor origin. The patient was treated with IV methylprednisolone, plasmapheresis, IVIG and Rituximab. Discussion: Donor-derived Alport syndrome is a rare finding in kidney transplant recipients, especially those with other primary diseases like FSGS. This case highlights the importance of surveillance biopsies in high-risk patients with de novo DSAs. Early detection of subclinical AMR and donor-derived pathology allows timely intervention, potentially preserving long-term graft function despite complex pathology.