Diagnostic Challenge for Anti-Glomerular Basement Membrane Disease: Pulmonary-Renal Syndrome in a Kidney Transplant Recipient with Alport Syndrome

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune condition, affecting approximately 1 in 1,000,000 people annually. In patients with Alport syndrome who undergo kidney transplantation, de novo anti-GBM disease may develop in up to 5% of cases and often leads to rapid graft loss. This response is thought to result from exposure to wild-type type IV collagen in the donor kidney, absent in the native kidneys of Alport patients. Diagnosis is difficult due to delayed onset and frequently undetectable circulating anti-GBM antibodies. We present a rare case of post-transplant anti-GBM disease manifesting as diffuse alveolar hemorrhage (DAH), highlighting diagnostic complexity and the need for clinical vigilance. Case Description: A 70-year-old woman with ESRD due to X-linked COL4A5 Alport syndrome and three prior kidney transplants (most recently in 2019) presented with acute shortness of breath and renal dysfunction. She required intubation and vasopressors for shock. Labs revealed leukocytosis (WBC 19.68), anemia (Hb 8.4), elevated BUN (105), creatinine (2.76 mg/dL; baseline 1.3), hematuria (3+), and a supratherapeutic tacrolimus level (50.7 ng/mL). Imaging showed bilateral infiltrates and diffuse ground-glass opacities. Bronchoscopy revealed hemosiderin-laden macrophages, consistent with DAH. Continuous renal replacement therapy was started for worsening renal function and volume overload. Despite negative anti-GBM serologies and inability to obtain a biopsy due to instability, empiric plasmapheresis was initiated. Repeat bronchoscopy showed decreased bleeding, but her respiratory and circulatory status deteriorated. She died on hospital day 8; blood cultures later grew ESBL-producing E. coli. Discussion: Post-transplant anti-GBM disease in Alport syndrome is a rare but severe complication caused by alloimmunization to type IV collagen. Diagnosis is challenging due to seronegativity—particularly in Alport patients whose antibodies often target the α5 rather than α3 chain. Though most cases occur within a year of transplant, delayed presentation is possible. DAH is a rare and previously unreported feature in this setting. Prognosis remains poor despite treatment. This case underscores the need for high clinical suspicion and early empiric therapy when biopsy is not feasible.