Proteinuria selectivity index predicts response to rituximab in adults with minimal change disease and focal segmental glomerulosclerosis

Allinovi, Marco; Trivioli, Giorgio; Lugli, Gianmarco; Villanti, Maurizio; Gianassi, Iacopo; Antognoli, Giulia; Romagnani, Paola; Vaglio, Augusto; Caroti, Leonardo; Cirami, Calogero

doi:10.1093/ndt/gfab323

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…Provided that this association is not driven by the lower baseline proteinuria per se , the mechanisms underlying this observation are to be clarified; putative factors include milder glomerular damage or better RTX pharmacokinetic profiles in patients with lower proteinuria. 30 , 31 This finding may also lead to speculations as to whether RTX dose may affect response, as already questioned in other glomerulonephritides. 25 , 32 In our study, where heterogeneous RTX dosing regimens were used, no clear dose-response association emerged, although in the context of an underpowered analysis.…”

Section: Discussionmentioning

confidence: 87%

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: 87%

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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“…In a study of 29 adult patients (15 MCD and 14 FSGS) who were treated with rituximab, all patients with PSI ≤0.20 attained remission while no patients with PSI >0.20 did. Responses to previous glucocorticoids and other immunosuppressive agents were lower in the PSI >0.20 group, and most of these patients suffered from FSGS [ 51 ]. Soluble urokinase plasminogen activator receptor (suPAR) is one proposed circulating factor.…”

Section: Introductionmentioning

confidence: 99%

Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group

Mirioglu,

Daniel-Fischer,

Berke

et al. 2024

Nephrology Dialysis Transplantation

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The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are entities without immune complex deposits which can cause podocyte injury, thus frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA), and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field.

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“…Many studies have found most of the patients who did not respond to RTX had advanced kidney impairment, while the renal function was mostly preserved among responders. Kidney dysfunction is associated with treatment resistance and is frequently observed in cases with non-selective proteinuria [ 33 – 35 ].The findings from Allinovi et al [ 36 ] highlighted a strong association between PSI and response to RTX in adults with MCD and FSGS. Proteinuria selectivity Index (PSI), the ratio of urinary immunoglobulin G clearance to transferrin clearance, may help identify patients for whom B-cell targeted therapy is effective.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of low-dose rituximab in minimal change disease and prevention of relapse

Zhang

Zhao

et al. 2023

BMC Nephrol

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Background Minimal change disease (MCD) is a major cause of nephrotic syndrome (NS) in children and a minority of adults. The higher tendency to relapse put patients at risk for prolonged exposure to steroids and other immunosuppressive agents. B cell depletion with rituximab (RTX) may be beneficial to the treatment and prevention of frequently relapsing MCD. Therefore, this study aimed to verify the therapeutic/preventive effects of low-dose RTX on the relapse in adult with MCD. Methods A total of 33 adult patients were selected for the study, including 22 patients with relapsing MCD in relapse treatment group who were treated with low-dose RTX (200 mg per week × 4 following by 200 mg every 6 months) and 11 patients in relapse prevention group with complete remission (CR) after steroid therapy were treated with RTX (200 mg ×1 every 6 months) for preventing the relapse of MCD. Results Of the 22 patients with MCD in relapse treatment group, there were 21 cases (95.45%) of remission [2 (9.09%) partial remission (PR), 19 (86.36%) CR], 1 (4.56%) no remission (NR) and 20 (90.90%) relapse-free. The Median duration of sustained remission was 16.3 months (3, 23.5 months, inter quartile range (IQR)). 11 patients in the relapse prevention group during a follow-up of 12 months (9–31 months) had no relapse. The average dose of prednisone in two groups after RTX treatment was significantly lower than before treatment. Conclusion The results of this study suggested low-dose RTX can significantly reduce relapse rate and steroid dose in adults with MCD with fewer side effects. Low-dose RTX regimens may be beneficial for the treatment of relapsing MCD in adults and may be the preferred regimen for patients at high risk for the development of adverse events from corticosteroids.

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Proteinuria selectivity index predicts response to rituximab in adults with minimal change disease and focal segmental glomerulosclerosis

Cited by 5 publications

References 14 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

Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group

Efficacy of low-dose rituximab in minimal change disease and prevention of relapse

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