Efficacy of Rituximab in Treatment-Resistant Focal Segmental Glomerulosclerosis With Elevated Soluble Urokinase-Type Plasminogen Activator Receptor and Activation of Podocyte β3 Integrin

Hladunewich, Michelle A.; Cattran, Dan; Sethi, Sanjeev; Hayek, Salim S.; Li, Jing; Wei, Changli; Mullin, Sarah; Reich, Heather N.; Reiser, Jochen; Fervenza, Fernando C.

doi:10.1016/j.ekir.2021.10.017

Cited by 11 publications

(16 citation statements)

References 41 publications

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Section: Discussionmentioning

confidence: 98%

“…To be clarified is also whether higher RTX doses may provide some benefits for SR patients, where response is poor. 33 Importantly, in the case series of Fernandez-Fresnedo et al, 23 the 3 SR patients who experienced remission after RTX received the highest cumulative dose. Furthermore, our data support a trend toward a transient and mild response at 3 months also in patients classified as NR at 6 months, leaving unanswered the question as to whether or not RTX dose may play a role in this context.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

Tedesco

Mescia

Pisani

et al. 2022

Kidney International Reports

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

Tedesco

Mescia

Pisani

et al. 2022

Kidney International Reports

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“…A refinement in the weekly monitoring of dipstick urine might be an approach to detect recurrence early. Further insights into the pathomechanism of FSGS and MCD, especially with respect to potential biomarkers such as anti-nephrin antibodies and suPAR may lead to a more individualized treatment approach and help identify patients with no or little benefit from therapy 11 . With respect to primary RTX resistance, advanced anti-CD20 antibodies have anecdotally been used in MCD and FSGS, but their role remains ill-defined in relation to RTX 57 , 58 .…”

Section: Discussionmentioning

confidence: 99%

“…Although suPAR levels are elevated in various other diseases, recent observations showed that suPAR levels are higher in patients with FSGS compared to other glomerular disease, and increased levels of suPAR are associated with progression to ESKD 10 . Additionally, in patients with FSGS and high levels of suPAR, rituximab was shown to be ineffective 11 . suPAR, together with other FSGS risk factors, may increase the pathogenicity of glomerular disease, for example by cooperating with a risk variant version of Apolipoprotein L1 (APOL1) 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

Repetitive administration of rituximab can achieve and maintain clinical remission in patients with MCD or FSGS

Osterholt¹,

Todorova²,

Kühne³

et al. 2023

Sci Rep

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Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are glomerulopathies associated with nephrotic syndrome. Primary forms of these diseases are treated with various regimes of immunosuppression. Frequently relapsing or glucocorticoid-dependent courses remain challenging. Here, a B-cell-depleting strategy with rituximab represents a salvage option although data are sparse in the adult population. In particular, there is limited evidence on the efficacy of restoring remission after initial successful treatment with rituximab and whether patients benefit from an individualized, relapse-based approach. We identified 13 patients who received multiple therapies with rituximab from the FOrMe-registry (NCT03949972), a nationwide registry for MCD and FSGS in Germany, or from the University Hospital of Cologne. Disease status, changes in serum creatinine, proteinuria, and time to relapse were evaluated. Relapse-free survival was compared to the patients’ previous therapy regimens. Through all treatment cycles, an improvement of disease activity was shown leading to a complete remission in 72% and partial remission in 26% after 3 ($$p<$$ p < 0.001) and 6 months ($$p<$$ p < 0.001). Relapse-free survival increased from 4.5 months (95%-CI 3–10 months) to 21 months (95%-CI 16–32 months) ($$p<$$ p < 0.001) compared to previous immunosuppression regimens with no loss in estimated glomerular filtration over time (p = 0.53). Compared to continuous B-cell depletion, an individualized relapse-based approach led to a reduced rituximab exposure and significant cost savings. Relapse-based administration of rituximab in patients with MCD/FSGS with an initial good clinical response did not result in a decreased efficacy at a median follow-up duration of 110 months. Thus, reinduction therapies may provide an alternative to continuous B-cell-depletion and reduce the long-term side effects of continuous immunosuppression.

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“…They did not find a correlation between the increased suPAR and decreased GFR, however, this study had a limitation in the number of patients (only 52 cases) [ 21 ]. A recent study showed that patients with treatment-resistant primary FSGS with a high suPAR level and evidence of podocyte activation were resistant to rituximab therapy [ 22 ]. The study by Winnicki et al showed that patients with FSGS presented significantly higher suPAR levels than patients with other glomerulonephritis and healthy individuals.…”

Section: Potential Circulating Permeability Factorsmentioning

confidence: 99%

Biomarkers in Primary Focal Segmental Glomerulosclerosis in Optimal Diagnostic-Therapeutic Strategy

Musiała

Donizy

Augustyniak−Bartosik

et al. 2022

JCM

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Focal segmental glomerulosclerosis (FSGS) involves podocyte injury. In patients with nephrotic syndrome, progression to end-stage renal disease often occurs over the course of 5 to 10 years. The diagnosis is based on a renal biopsy. It is presumed that primary FSGS is caused by an unknown plasma factor that might be responsible for the recurrence of FSGS after kidney transplantation. The nature of circulating permeability factors is not explained and particular biological molecules responsible for inducing FSGS are still unknown. Several substances have been proposed as potential circulating factors such as soluble urokinase-type plasminogen activator receptor (suPAR) and cardiolipin-like-cytokine 1 (CLC-1). Many studies have also attempted to establish which molecules are related to podocyte injury in the pathogenesis of FSGS such as plasminogen activator inhibitor type-1 (PAI-1), angiotensin II type 1 receptors (AT1R), dystroglycan(DG), microRNAs, metalloproteinases (MMPs), forkheadbox P3 (FOXP3), and poly-ADP-ribose polymerase-1 (PARP1). Some biomarkers have also been studied in the context of kidney tissue damage progression: transforming growth factor-beta (TGF-β), human neutrophil gelatinase-associated lipocalin (NGAL), malondialdehyde (MDA), and others. This paper describes molecules that could potentially be considered as circulating factors causing primary FSGS.

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Efficacy of Rituximab in Treatment-Resistant Focal Segmental Glomerulosclerosis With Elevated Soluble Urokinase-Type Plasminogen Activator Receptor and Activation of Podocyte β3 Integrin

Cited by 11 publications

References 41 publications

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

Repetitive administration of rituximab can achieve and maintain clinical remission in patients with MCD or FSGS

Biomarkers in Primary Focal Segmental Glomerulosclerosis in Optimal Diagnostic-Therapeutic Strategy

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