B279 - Use of Daratumumab and Empagliflozin for the Treatment of Pediatric Post-Transplant Severe Recurrent Nephrotic Syndrome: A Case Report

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Author Block: S. Katz, J. Byrns, M. Harris, Pharmacy, Duke University Hospital, Durham, NC
*Purpose: Recurrence of nephrotic syndrome (NS) after kidney transplant (KTx) poses a major challenge that may lead to early graft loss despite current therapies. We report a severe case of recurrence in a pediatric patient successfully treated with daratumumab (DARA) and empagliflozin (EMPA) in addition to conventional plasmapheresis (PLEX), IVIG, and rituximab (RTX).
*Methods: A 17-year-old male underwent KTx for late steroid-resistant NS from FSGS with C1q nephropathy and anti-nephrin autoantibodies. NS was diagnosed at age 2 and ultimately became refractory to steroids, cyclosporine, mycophenolate (MMF), RTX, PLEX, and IVIG. The patient was initiated on dialysis and received a KTx the following year. Induction immunosuppression (IS) was rabbit anti-thymocyte globulin. Maintenance IS was steroids, MMF, and tacrolimus.
*Results: Post-KTx course was complicated by early recurrence of NS within 12 hours of KTx and resultant graft dysfunction requiring dialysis. Urine protein-creatinine ratio (UPCR) peaked at >20,000 mg/g (Figure 1). Emergent PLEX was initiated post-operative day (POD) 1, and the patient received RTX 375 mg/m² on POD 2 and 17. DARA 16 mg/kg subQ for 4 weekly doses was started POD 6. UPCR and SCr decreased with treatment, and the patient was discharged on POD 20 with UPCR ~3,000 mg/g and normal SCr. On POD 90, biopsy was performed due to worsening proteinuria and was notable for mild, patchy podocyte foot process effacement and punctate IgG staining of podocytes, consistent with the presence of anti-nephrin autoantibodies. On POD 132, DARA 16 mg/kg was restarted for 4 biweekly doses. UPCR remained ~3,000-5,000 mg/g. The patient received an additional dose of RTX 375 mg/m² on POD 202. On POD 208, EMPA 10 mg daily was initiated and later increased to 20 mg daily on POD 255. Due to worsening proteinuria to >10,000 mg/g, PLEX was again resumed with plans to convert to biweekly DARA. Despite refractory proteinuria, the patient has remained off dialysis since index hospitalization. DARA infusions were well-tolerated. Infectious complications were limited to a brief period of low-level BK viremia, and no urinary tract infections were noted with the addition of EMPA.
*Conclusions: This case of severe recurrent NS after KTx highlights the challenge of achieving sustained reduction in proteinuria. While some data exists on the use of DARA for treating recurrent NS, to our knowledge, this case describes the first use of EMPA in combination with DARA. Further investigation into the role of these agents in managing post-KTx NS recurrence that fails to respond to conventional therapy is warranted.
Figure 1.