Abstract Introduction Anti-GBM Disease is a small vessel vasculitis where autoantibodies directed against the alveolar and glomerular basement membranes cause diffuse alveolar hemorrhage (DAH) and nephritic syndrome. Individuals with Alport Syndrome (AS) suffer from a genetic disorder caused by mutations in Type IV collagen that leads to end-stage-renal disease (ESRD). Patients with AS who undergo renal transplant may develop anti-GBM antibody formation against the antigenic type IV collagen in the transplanted kidney, called “Alport Post-Transplant Nephritis”. Case A 70-year-old female with history of ESRD secondary to AS, and three prior kidney transplants (most recently in 2019, the priors were complicated by acute rejection) presented with 1 day of dyspnea and hemoptysis. Labs revealed acute kidney injury (creatinine 2.76 mg/dl; baseline 1.3) and glomerular hematuria (3+ on dipstick, dysmorphic red blood cells on microscopy). CT scan of the thorax demonstrated bilateral diffuse ground glass opacities. The patient was intubated for severe hypoxemic respiratory failure. Bronchoscopy demonstrated macrophages with hemosiderin deposition and increasingly bloodier return of serial aliquots consistent with DAH. Serum anti-neutrophil cytoplasmic antibody (ANCA) testing and an anti-GBM enzyme immunoassay panel were negative. Vasopressors were started for shock. Despite negative serology and inability to obtain a kidney transplant due to instability, empiric plasmapheresis was initiated given the known risk of nephritic syndrome in AS transplant recipients. Repeat bronchoscopy demonstrated improved airway bleeding and the patient’s renal function improved. Unfortunately, her circulatory status deteriorated, and the patient ultimately expired from sepsis secondary to E.coli bacteremia. Discussion Anti-GBM disease manifests as a nephritic syndrome, accompanied by alveolar hemorrhage in 30-60% of cases. 5% of patients with AS experience “Alport Post-Transplant Nephritis,” which classically presents with renal findings within the first year of transplant, though delayed cases such as this one are possible. DAH is a previously unreported feature among patients with Alport Post-Transplant Nephritis, who tend to make antibodies solely against the donor type IV collagen in the graft kidney, resulting in a pure nephritic syndrome. Anti-GBM serology is often negative among those with AS, as in this case, who make alloantibodies against the alpha 5 chain of type IV collagen instead of the Goodpasture Antigen. This case highlights an atypical presentation of Anti-GBM disease in the setting of AS, given the initial symptom presentation with prominent pulmonary symptoms and onset years after several transplants, as well as the need for high clinical suspicion and empiric therapy when kidney biopsy is not feasible. This abstract is funded by: None
Gay et al. (Fri,) studied this question.