Atypical HUS Unmasked by Infection and Calcineurin Inhibitors Post Lung Transplant

Abstract

<h3>Introduction</h3> Lung transplant recipients are maintained on multiple lifelong immunosuppressive medications including steroids, calcineurin inhibitors (CNI), and antimetabolite (AM) medications. We report a unique case of a double lung transplant (DLT) recipient developing thrombotic microangiopathy (TMA) from atypical hemolytic uremic syndrome (aHUS) unmasked by infection and CNI therapy. <h3>Case Report</h3> 63-year-old male developed delirium and thrombocytopenia after initiation of CNI therapy with tacrolimus post DLT. Evaluation was otherwise negative and patient improved with cessation of therapy. CNI was switched to cyclosporine without further issues. Four-week biopsy was negative for acute cellular rejection. Five days later, he presented with hypoxia, dyspnea, dizziness, confusion, and impaired gait. His immunosuppressive regimen included prednisone & cyclosporine. His AM therapy was held for leukopenia. All testing and imaging were negative apart from bronchial lavage cultures positive for pseudomonas, klebsiella, and parainfluenza. Appropriate antibiotics and antiviral therapies were started. He developed delirium, acute kidney injury, hemolysis, and thrombocytopenia. Impression was CNI-induced TMA, and CNI was held. All additional work up was negative including shiga-like toxin producing E.Coli. He failed to improve with removal of offending agent and concern was for aHUS given complement panel was suggestive of alternative pathway dysregulation (absent AH50, normal C4 and decreased factors B and H). Patient did not respond to plasmapheresis, and eculizumab was started. He remained thrombocytopenic with positive hemolytic parameters despite 2 doses of therapy. Complement genetic panel testing is pending. Treatment is now held due to respiratory failure and septic shock. <h3>Summary</h3> aHUS is a rare form of TMA, associated with excess activation of the alternate complement pathway which is part of innate immunity. It usually responds to treatment with eculizumab, an anti-C5 monoclonal antibody that inhibits terminal complement complex generation. Our case is inconsistent with secondary HUS from drugs or solid organ transplant and has failed standard aHUS therapy. This is a complex and uniquely challenging case, limited second line options are available including a recently approved long-acting C5 complement inhibitor, which is under review at our institution.