Focal segmental glomerular sclerosis can be effectively treated using an intensive B-cell depletion therapy.

Abstract

Focal segmental glomerular sclerosis (FSGS) is a histologic lesion rather than a specific disease entity and represents a cluster of different conditions affecting both children and adults that includes primary, secondary and genetically mediated forms. These forms can be distinguished by electron microscopy and genetic assessment and show different responsiveness to steroids and immunosuppressants. Despite some promising effects of rituximab in nephrotic syndrome in children, the results in adults with FSGS are disappointing. Our group previously explored the effectiveness of rituximab in eight adult patients with unselected forms of FSGS and achieved a consistent reduction in proteinuria in one case. Following this experience, we developed an alternative therapeutic option intended to enhance the potential of rituximab with the support of other synergic drugs. We herein report the results of this therapeutic protocol (six administrations of rituximab plus two of intravenous cyclophosphamide plus glucocorticoids) in seven prospectively enrolled patients with extensive podocyte effacement and recurrent relapses or steroid dependence. Patients had a median baseline serum creatinine level of 2.2mg/dl (range 1-4.7) that decreased to 1.1mg/dl (range 0.9-2.2) and 1.1mg/dl (range 0.75-2.21) after 3 and 6months, respectively, and remained unchanged at 12months. Three of five patients with renal failure turned to normal function while the other two patients maintained a stable impairment after 18 and 52months. The median proteinuria decreased from 6.1g/24h to 3.5, 3.5 and 1.9g/24h at 3, 6 and 12months, respectively. Specifically, five of seven patients had a partial response at 12months and became non-nephrotic. One of them had a complete response at 18months and was still in complete remission at the last follow-up visit at 36months. Proteinuria persisted unchanged in two of seven patients with a genetic-related disease. No serious late adverse events were observed. Our results show that intensive B-cell depletion therapy is able to reverse the nephrotic syndrome of steroid-dependent or frequently relapsing adult patients with putatively idiopathic FSGS (i.e. with extensive podocyte effacement).