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

Dario Roccatello; Alessandra Baffa; Carla Naretto; Antonella Barreca; Raffaella Cravero; Elisabetta Roscini; Savino Sciascia; Roberta Fenoglio

doi:10.1093/ckj/sfac207

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

Clin Kidney J. 2022 Sep 12;16(8):1258-1264. doi: 10.1093/ckj/sfac207. eCollection 2023 Aug.

Authors

Dario Roccatello¹, Alessandra Baffa¹, Carla Naretto¹, Antonella Barreca², Raffaella Cravero³, Elisabetta Roscini⁴, Savino Sciascia¹, Roberta Fenoglio¹

Affiliations

¹ University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnet and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, 10154 Turin, Italy.
² Division of Pathology, Città della Salute e della Scienza Hospital and University of Turin, Turin, Italy.
³ Unit of Nephrology and Dialysis, Ospedale degli Infermi, Biella, Italy.
⁴ Unit of Nephrology and Dialysis, Casale Monferrato and Novi Ligure Hospitals, Alessandria, Italy.

Abstract

Background: 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.

Results: Patients had a median baseline serum creatinine level of 2.2 mg/dl (range 1-4.7) that decreased to 1.1 mg/dl (range 0.9-2.2) and 1.1 mg/dl (range 0.75-2.21) after 3 and 6 months, respectively, and remained unchanged at 12 months. Three of five patients with renal failure turned to normal function while the other two patients maintained a stable impairment after 18 and 52 months. The median proteinuria decreased from 6.1 g/24 h to 3.5, 3.5 and 1.9 g/24 h at 3, 6 and 12 months, respectively. Specifically, five of seven patients had a partial response at 12 months and became non-nephrotic. One of them had a complete response at 18 months and was still in complete remission at the last follow-up visit at 36 months. Proteinuria persisted unchanged in two of seven patients with a genetic-related disease. No serious late adverse events were observed.

Conclusions: 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).

Keywords: cyclophosphamide; focal segmental glomerulosclerosis; glucocorticoids; renal biopsy; rituximab.