Patient with THSD7A Antibody-Positive Primary Membranous Nephropathy (PMN) Refractory to Treatment with Rituximab Achieves Immunologic and Partial Clinical Remission Using the Ponticelli Regimen

Introduction: Thrombospondin type 1 domain-containing protein 7A (THSD7A) antibodies are detected in approximately 2% of cases of PMN. Though ideal initial treatment in PMN is debated, many clinicians opt for rituximab due to its efficacy and favorable side effects. Little is known regarding optimal therapy to induce remission following rituximab failure, and even less so withTHSD7A antibodies. Case Description: 48 year-old lady with a past history of Hashimoto’s thyroiditis was transferred to our facility for an escalation in care due to complications from PMN. Patient diagnosed by a private nephrology group with PLA2R negative membranous nephropathy 6 months prior and after a negative malignancy screen was started immediately on rituximab. On presentation to our center, patient was 50 lbs over baseline weight and had developed a complete right sided hydropneumothorax and a left sided pleural effusion. Serum albumin was 0.8 gm/dL, and 24-hour urine protein was greater than 40 grams. Serum creatinine was 0.8 mg/dL. CD19 and CD20 levels were undetectable 6 months after rituximab induction. Decision was made to repeat the biopsy and stain for alternate antibodies to confirm diagnosis of PMN. Biopsy resulted positive for THSD7A staining and circulating serum THSD7A antibodies were positive. Modified Ponticelli regimen was initiated. At the end of 6 month treatment, serum THSD7A antibodies were undetectable consistent with immunologic remission and the patient had achieved a substantial clinical response with serum albumin improved to 2.8 mg/dL and urine protein/creatinine ratio improved to 5.37 gm/gm. Patient continues to show clinical improvement and achieved partial clinical remission 5 months after treatment end with 24 hour urine protein of 2.54 gm. Serum creatinine remained unchanged through treatment. Discussion: Little information exists on Rituximab refractory membranous nephropathy and even less so on THSD7A PMA. At 6 months post rituximab infusion, our patient was CD19 and CD20 undetectable confirming adequate Rituximab induction but still had circulating THSD7A antibody on re-biopsy. Immunologic and partial clinical remission was induced with modified Ponticelli regimen. Our case emphasizes that the Ponticelli regime may be effective in cases of rituximab refractory membranous nephropathy.