Refractory Primary Podocytopathy: Any Role for Daratumumab?

Introduction: Primary Podocytopathy is an autoimmune injury of the podocytes with a characteristic histopathologic lesion of focal and segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). It is associated with abrupt onset of nephrotic syndrome and treated with corticosteroid and anti-B cell therapy. Case Description: 30-year-old male previously healthy presented with peripheral edema and shortness of breath, his urine protein to creatinine ratio (UPCR) was 5.8 g/g for which he underwent kidney biopsy showing MCD. The patient had a complete remission following a prednisone course however he relapsed at 4 months (during the prednisone tapering) and had a prolonged course of steroid-refractory nephrotic syndrome a repeat kidney biopsy showed FSGS tip lesion. The immunosuppressive therapies and adverse events (AE) were sequentially: 1. Prednisone 80mg for additional 4 months (AE: retinal detachment) 2. Rituximab 1g x2 with successful depletion of CD19+ B cells without decrease in proteinuria (AE: hypogammaglobulinemia) 3. Obinutuzumab 1g x2 followed by 1g at 6 months with worsening proteinuria to 6.4 g/g (AE: fungal pneumonia) 4. Repeat steroid course, tacrolimus (trough: 5-7 μg/l) and Dapagliflozin 10 mg daily (AE: AKI) The patient received Daratumumab 1800mg SC weekly for 8 doses with improvement of the UPCR to to 0.89 g/g, increase albumin to 3.4 g/dL and resolution of the edema that was persistent for more than 2 years. Discussion: Guidelines recommend high-dose steroids as first-line the treatment for primary FSGS and MCD. Tip glomerular lesion has been described to respond to glucocorticoid therapy more than patients with the other FSGS variants. Calcineurin inhibitors and rituximab (anti-CD20 mAb) can be used for the treatment of frequently relapsing MCD or FSGS. Although not yet widely use, the anti-CD38 mAb, Daratumumab, has been used in some cases of post-transplant recurrent FSGS with promising results. Further randomized control trials of patient with multi-drug resistant primary podocytopathy are needed to determine the efficacy of daratumumab.Clinical course and treatment