A Diagnostic Dilemma: Renal Limited Thrombotic Microangiopathy in a Stem-Cell Transplant Recipient

Introduction: Kidney disease following hematopoietic stem cell transplantation is attributed to a variety of etiologies Case Description: A 59 year old male with history of diffuse large B cell lymphoma was seen in consultation for an elevated serum creatinine (SCr) of 1.8 mg/dL. He had previously failed therapy with multiple treatments, initially Rituximab, Etoposide phosphate, Prednisone, Vincristine sulfate, Cyclophosphamide, Doxorubicin hydrochloride (R-EPOCH), followed by CAR-T therapy, and most recently allogenic stem cell transplant. He was being treated with Epcoritamab (anti-CD20 agent) at time of consultation. He was not on a Calcineurin inhibitor. Urinalysis and imaging studies were unremarkable. Urine total protein creatinine ratio was mildly elevated at 0.32 mg/mg, with no monoclonal protein on urine electrophoresis. There were no schistocytes on peripheral smear and no thrombocytopenia on complete blood count. LDH was mildly elevated to 340. A renal biopsy was performed given no clear etiology of SCr elevation. Renal biopsy showed diffuse double contouring of glomerular basement membranes (arrows), focal segmental mesangiolysis with red cell fragmentation and microaneurysm formation (circle) and focal segmental endocapillary hypercellularity. There were no immune complexes by immunofluorescence. These findings were indicative of chronic endothelial injury (so-called Chronic Thrombotic Microangiopathy [TMA]). Discussion: Early detection of transplant associated TMA is critical given potential for multiple organ dysfunction syndrome and death. Management options include Rituximab, Defibrotide and Eculizumab but evidence is limited to small cohorts and observational data. The patient was planned to start Eculizumab, and renal function remained stable at follow up visit. This case highlights the importance of renal biopsy in making this diagnosis since there were no obvious clues to suggest TMA from history and lab investigations.