Rituximab Treatment for Relapsing Minimal Change Disease and Focal Segmental Glomerulosclerosis: A Systematic Review

Abstract

Background: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remain a therapeutic challenge, since steroids and other immunosuppressive agents exhibit an unfavorable adverse event spectrum. The aim of this review was to systematically summarize and analyze data from preexisting studies reporting the outcome of rituximab (RTX) treatment in these patients. Methods: Study data on adult patients with either steroid-dependent or frequently relapsing MCD/FSGS were identified by a PubMed and Embase search. The number of relapses was calculated and the use of immunosuppressive co-medication prior to and after RTX treatment was quantified. Results: We identified14 studiesincluding 86 patients with frequently relapsing and steroid-dependent MCD or FSGS. Treatment with RTX reduced the number of relapses per year from 1.3 (0-9) relapses prior to treatment compared to 0 (0-2) after therapy (p < 0.001). Proteinuria decreased from 2.43 (0-15) g/day to 0 (0-4.89) g/day (p < 0.001), while serum albumin increased from 2.9 (1.2-4.6) at baseline to 4.0 (1.8-5.09) g/l after RTX (p = 0.001). The use of immunosuppression used at the time of RTX administration was also reduced after RTX therapy (p < 0.001). Baseline serum albumin was lower (p = 0.018), whereas the number of immunosuppressants prior to RTX was higher (p = 0.018) in patients with relapse after RTX. Conclusions: The published data suggest that RTX is effective in reducing the number of relapses and sparing immunosuppression in frequently relapsing and steroid-dependent nephrotic syndrome due to MCD and FSGS. These promising findings have to be confirmed in controlled and prospective studies.

Synaptopodin is upregulated by IL-13 in eosinophilic esophagitis and regulates esophageal epithelial cell motility and barrier integrity

“…Idiopathic nephrotic syndrome is a clinical syndrome associated with a variety of kidney pathologies, including minimal change disease (MCD) (34), in which there is effacement of the foot processes of podocytes, leading to loss of epithelial integrity and increased permeability associated with proteinuria (35,36). Importantly, MCD can be successfully treated by immunosuppressive drugs, suggesting that immunologic responses are critical (23,37,38). Numerous reports associate MCD with atopy, as evidenced by elevated expression of IgE and increased prevalence of atopy in patients with MCD compared with control subjects (39)(40)(41)(42).…”

Causes and pathogenesis of focal segmental glomerulosclerosis

“…Interestingly, rituximab (a chimeric monoclonal antibody against CD20, which is expressed on B cells) has shown benefit in reducing incidence of relapses in some children and adults with FSGS. 27 Whether this reduction could be the result of effects of rituximab on B cells, or direct effects on podocytes that protect the cytoskeleton and prevent apoptosis, is not known. 27 …”

Rituximab in Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis

“…Moreover, a high number of immunosuppressants used prior to RTX revealed a higher risk of relapse in a recent analysis of reported experience. This finding may be attributable to a more severe disease course entailing more immunosuppressive strategies [14]. Steroid-resistant forms of MCD and FSGS are underrepresented so far.…”

“…In addition, the number of immunosuppressants could be significantly reduced following therapy. However, there was an association between a high number of immunosuppressive agents used before RTX and an increased risk of relapse after therapy [14]. …”