Rituximab Treatment of Adult Patients with Steroid-Resistant Focal Segmental Glomerulosclerosis

Abstract

Background and objectives: Isolated case reports have shown a beneficial effect of rituximab on pediatric patients with primary FSGS, but there is no information about rituximab treatment of FSGS in adults.Design, setting, participants, & measurements: All patients who had biopsy-proven FSGS and were treated with rituximab in Spain were identified, independent of their positive or negative response, among the nephrology departments that belong to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Their characteristics and outcome after rituximab treatment were studied.Results: Eight patients were identified. Rituximab failed to improve nephrotic syndrome in five of eight patients, who continued to show massive proteinuria and exhibited a rapidly deteriorating renal function in two cases. Among the remaining three patients, two of them showed an improvement of renal function and a remarkable proteinuria reduction and one experienced a beneficial but transitory effect after rituximab. There were no differences in clinical or laboratory characteristics or in the CD20 B lymphocyte count after rituximab between these three patients and the five who had a negative response. The only difference was in the regimen of rituximab administration: Whereas the five patients with a negative response received only four weekly consecutive infusions of 375 mg/m 2 , the three remaining patients received additional doses of rituximab.Conclusions: Only a minority (three of eight) of patients in our series of adult patients with FSGS showed a positive influence of rituximab. More studies are necessary to characterize further the optimal dosages and the mechanisms of action of rituximab in FSGS.

Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

“…FSGS is more common in the adult population and can be a challenge not only in the native kidney, but as recurrent disease in the renal allograft. The use of RTX in primary FSGS in adults has had variable, but mostly negative results in small case series [90], [91] and [92]. However, it may be useful in treating posttransplant relapse [93], [94] and [95].…”

IgM Contributes to Glomerular Injury in FSGS

“…9,10 Furthermore, recent reports suggest that rituximab, a mAb to CD20 that depletes mature B cells, may be beneficial in some patients with the nephrotic syndrome. [11][12][13][14][15][16] However, the mechanisms by which rituximab alleviates the nephrotic syndrome are not yet known. Recent work has demonstrated that "natural antibody" contributes to tissue injury in a number of different diseases.…”

Rituximab in immunologic glomerular diseases

“…[30][31][32][33][34] On the contrary, Spanish Group for the Study of Glomerular Diseases (GLOSEN) reported that rituximab was successful in improving renal function and achieving a sustained reduction in proteinuria in two of eight adult patients with FSGS. 35 No differences were observed in CD20 + B lymphocyte count among the responder and non-responders. It is therefore plausible that rituximab may induce anti-proteinuric effect through mechanisms independent of B-cell depletion.…”