Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance

Guitard, Joëlle; Hebral, Anne-Laure; Fakhouri, Fádi; Joly, Dominique; Daugas, Éric; Rivalan, Joseph; Guigonis, Vincent; Ducret, F; Presne, Claire; Pirson, Yves; Hourmant, Maryvonne; Glachant, Jean-Claude; Vendrely, Benoı̂t; Moranne, Olivier; Faguer, Stanislas; Chauveau, Dominique

doi:10.1093/ndt/gfu209

Cited by 55 publications

(56 citation statements)

References 27 publications

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“…22,23 However, persistent remission induced by RTX can be maintained in some patients with INS also after CD19 + recovery. 13,24 This observation suggests a disease-modifying effect of RTX in INS that goes beyond total B cell depletion. A single study showed in vitro a direct effect of RTX on podocyte function.…”

Section: Discussionmentioning

confidence: 94%

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

Colucci¹,

Carsetti²,

Cascioli

et al. 2015

JASN

170

165

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The pathogenesis of nephrotic syndrome is unclear. However, the efficacy of rituximab, a B cell-depleting antibody, in nephrotic syndrome suggests a pathogenic role of B cells. In this retrospective study, we determined by flow cytometry levels of B and T cell subpopulations before and after rituximab infusion in 28 pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome. At baseline, patients had lower median percentages of transitional and mature B cells than age-matched healthy controls (P,0.001). Rituximab induced full depletion of B cells (,1% of lymphocytes). At 1 year, most patients exhibited complete total and mature B cell recovery, whereas memory B cell subsets remained significantly depleted. Total T cell concentration did not change with rituximab, whereas the CD4 + /CD8 + T cell ratio tended to increase. Fourteen patients relapsed within 24 months, with a median follow-up of 11.2 months (interquartile range, 8-17.7 months). We observed no difference at baseline between nonrelapsing and relapsing patients in several clinical parameters and cell subset concentrations. Reconstitution of all memory B cell subpopulations, number of immunosuppressive drugs, and dose of tacrolimus during the last 4 months of follow-up were predictive of relapse in univariate Cox regression analysis. However, only delayed reconstitution of switched memory B cells, independent of immunosuppressive treatment, was protective against relapse in multivariate (P,0.01) and receiver operator characteristic (P,0.01 for percentage of lymphocytes; P=0.02 for absolute count) analyses. Evaluation of switched memory B cell recovery after rituximab may be useful for predicting relapse in patients with nephrotic syndrome.

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Section: Discussionmentioning

confidence: 94%

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

Colucci¹,

Carsetti²,

Cascioli

et al. 2015

JASN

170

165

View full text Add to dashboard Cite

show abstract

“…The largest adult cohort of patients with biopsy confirmed that minimal-change glomerulopathy treated with rituximab had a 61% (25/41) complete clinical response with 52% of responders relapsing and had successful re-treatment with rituximab [24]. Similar recent work of 16 adults, one of whom was corticosteroid-resistant, showed full remission in 81% (13/16) of patients with 7 eventually relapsing after 9–28 months with a mean follow-up of 44 months [19].…”

Section: Discussionmentioning

confidence: 99%

The Evolving Role of Rituximab in Adult Minimal Change Glomerulopathy

Brown

Jobson²,

Schober³

et al. 2017

Am J Nephrol

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Background: Minimal-change glomerulopathy is defined histologically by the presence of normal glomeruli on light microscopy and diffuse podocyte effacement on electron microscopy. Although effective in children, corticosteroid treatment in adults is more variable and time to response can be prolonged. Data to support rituximab use in adults with corticosteroid-dependent or resistant minimal-change glomerulopathy are limited. Here, we describe the clinical course of adults with corticosteroid-dependent or -resistant minimal-change glomerulopathy who received rituximab. Methods: Demographic and clinical data were collected and analyzed from all adult patients with native kidney, biopsy-proven, minimal-change glomerulopathy who were administered rituximab between 2009 and 2014 and cared for at the UNC Kidney Center. Results: Ten patients with corticosteroid-resistant (n = 5) or corticosteroid-dependent (n = 5) idiopathic minimal-change glomerulopathy were treated with rituximab between 2009 and 2014. Rituximab treatment induced remission in all 10 patients with a median time to remission of 2 months. The median time from rituximab to corticosteroid discontinuation was 3.5 months. The median remission time was 29 months and follow-up time was 39.5 months. No serious adverse events attributable to rituximab were observed. Conclusion: Rituximab induced remission in all patients with corticosteroid-dependent or -resistant minimal-change glomerulopathy, and may hold great therapeutic potential with good efficacy and minimal toxicity. Mounting evidence implies that a well-conducted randomized controlled clinical trial using rituximab in adults with minimal-change glomerulopathy in both corticosteroid-resistant and corticosteroid-dependent patients is warranted.

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“…In general, the mechanism of MCNS is not precisely known, although it is hypothesized that the induction of CD80 in podocytes is triggered by circulating cytokines, microbial products or allergens and is perpetuated by regulatory T cell dysfunction or impaired autoregulatory podocyte functions (2,7). However, recent reports or evidence from clinical practice suggest that rituximab, an anti-CD20 monoclonal antibody, ameliorated the refractory nephrotic syndrome, including frequently relapsing MCNS (8,9). The etiological analysis is difficult because rituximab leads to direct lysis of B cells only, not T cells.…”

Section: Discussionmentioning

confidence: 99%

Minimal Change Nephrotic Syndrome Which Was Most Likely Caused by Chronic Sinusitis

et al. 2015

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A 33-year-old Japanese man was admitted with severe edema, and a renal biopsy confirmed minimal change nephrotic syndrome (MCNS). CT revealed his severe chronic sinusitis, and he first received antimicrobial therapy, which resulted in decreased proteinuria. The surgical operation for sinusitis resulted in the complete disappearance of proteinuria without corticosteroid or immunosuppressant therapy within one week. MCNS may be triggered by infection, but there are no previously reported cases of MCNS that is completely remitted by infection control alone. Therefore, we herein report the first case of MCNS that attained complete remission following therapy for chronic sinusitis alone, which suggests a strong etiology of chronic sinusitis for MCNS.

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Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance

Abstract: RTX is safe and effective in adult patients with MCNS and could be an alternative to steroids or CNIs in patients with a long history of relapsing MCNS.

Cited by 55 publications

References 27 publications

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

The Evolving Role of Rituximab in Adult Minimal Change Glomerulopathy

Minimal Change Nephrotic Syndrome Which Was Most Likely Caused by Chronic Sinusitis

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