Membranous Glomerulopathy After Hematopoietic Stem-Cell Transplant in a Patient with Sickle Cell Disease

Introduction: Membranous Glomerulopathy (MGN) Post-Hematopoietic Stem Cell Transplant (HSCT) in a Sickle Cell Disease (SCD) Patient is a rare but clinically significant scenario that raises several important considerations. MGN post-HSCT usually occurs months to years' post-transplant. Often considered a manifestation of chronic graft-versus-host disease (cGVHD). MGN may also result from Immune reconstitution with donor-derived lymphocytes attacking host tissues, chronic infections (e.g., hepatitis B/C, CMV) or medications (e.g., calcineurin inhibitors). Early recognition and targeted treatment are crucial to prevent irreversible organ damage. Case Description: Patient is a 23-year-old female with a history of sickle cell disease, status post-MUD HSCT in April 2021, HTN, obesity, GAD, and CVA in 2015 without residual effects who was admitted with AKI, nephrotic syndrome in the setting of fever, CMV viremia, and ocular and throat strep pyogenes infection. Serum creatinine was 4.28 mg/dL up from baseline 0.74 mg/dL. Serum albumin was <1.5 g/dL, C3 122.9, C4 37.9 and WBC 27.3. UPCR was 52 g/g. There was 46,149 mg of proteinuria on 24-hour collection. CMV and HBV were negative. Kidney biopsy revealed collapsing FSGS (ApoL1-mediated; ApoL1 genotype G1/G2), Membranous Nephropathy and Severe Acute Tubular Injury. PLA2R, NELL1, EXT1 and THSD7a staining negative on biopsy. Patient Proteinuria responded to Rituximab therapy, decreasing from >46g to 4.4 g on 24hr Urine studies. Subsequently, the patient has been managed with RAAS inhibition and SGLT2 inhibition therapy for Proteinuria and loop diuretic for edema. Discussion: Membranous Glomerulopathy in a post-HSCT sickle cell patient is a rare but important complication. This case is unique in the complexity of the patient's possible etiologies-ranging from APOL1 mediated, CMV viremia, medication induced to acute MSSA bacteremia. Early diagnosis via biopsy and appropriate immunosuppressive treatment are key to preserving renal function.