Obinutuzumab for refractory minimal change disease in obese patients: a case series

Minimal change disease (MCD) is a common cause of nephrotic syndrome in adults. Rituximab, a type I anti-CD20 antibody, is effective in many cases, but up to 40% of patients show an insufficient or transient response. Obesity, a frequent comorbidity, is associated with chronic low-grade inflammation and B-cell dysfunction, which may contribute to suboptimal treatment outcomes. Obinutuzumab, a type II anti-CD20 antibody, induces more profound B-cell depletion than rituximab. We report two obese patients (BMI 32.10 and 42.45 kg/m²) with biopsy-confirmed MCD who had an insufficient response to multiple immunosuppressive therapies, including rituximab. Patient 1 achieved complete remission with corticosteroids and tacrolimus; obinutuzumab (1 g) was added to enable rapid steroid withdrawal due to severe corticosteroid-induced acne. He remained in remission for >26 months after obinutuzumab, with CD19⁺ B-cell counts showing complete depletion (0 cells/μL), a rise to 103 cells/μL at 9 months (prompting a second dose). Patient 2 received obinutuzumab (1 g) for active disease after rituximab failure. He achieved complete remission but relapsed after immunosuppressant withdrawal. CD19⁺ B-cells had reconstituted to 75 cells/μL at relapse; a second obinutuzumab dose re-induced depletion (0 cells/μL) and remission, which was maintained at last follow-up. These observations suggest that obinutuzumab may induce and sustain remission in some obese patients with rituximab-insufficient MCD, and that obesity should be considered a potential modifier of treatment response in MCD.