Successful use of obinutuzumab in focal segmental glomerulosclerosis with inadequate response to rituximab: a case report

Introduction: Podocytopathies such as minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remain therapeutic challenges in adults. Although corticosteroids and rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, are effective in most patients, up to 10% show resistance or relapse despite B-cell depletion. Obinutuzumab (OBZ), a humanized type II anti-CD20 monoclonal antibody, achieves deeper and more sustained B-cell depletion and may overcome RTX inadequate response. Case report: A 33-year-old woman presented with nephrotic syndrome (proteinuria 7.1 g/24 h, serum albumin 2.6 g/dL, preserved renal function). Kidney biopsy revealed primary FSGS. She achieved only partial remission with corticosteroids and cyclosporine. RTX (1 g × 2 doses) induced transient peripheral B-cell depletion but no complete remission. A second biopsy excluded chronic changes, and genetic testing for hereditary podocytopathy was negative. Thus 67 weeks after diagnosis and initial treatment with persistent proteinuria > 1g/24 h and hypoalbuminemia, the patient received OBZ (1 g × 2 doses, two weeks apart). Two months later, she achieved complete remission (proteinuria 0.2 g/24 h, serum albumin 3.7 g/dL), with sustained B-cell depletion and no adverse events. A repeat administration of OBZ (1 g) was performed 10 months later due to B-cell repopulation, rising proteinuria (0.6 g/24 h), and mild hypoalbuminemia (serum albumin 3.4 g/dL), successfully re-inducing complete remission (proteinuria 0.2 g/24 h, serum albumin 3.8 g/dL). Discussion: This case illustrates the potential of OBZ as an effective therapeutic option in podocytopathies with RTX inadequate response. The superior efficacy of OBZ may result from enhanced antibody-dependent cellular cytotoxicity, depletion of tissue-resident B cells, and reduced immunogenicity compared with RTX. OBZ may thus offer an alternative in refractory MCD/FSGS.