Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy

Fervenza, Fernando C.; Appel, Gerald B.; Barbour, Sean J.; Rovin, Brad H.; Lafayette, Richard A.; Aslam, Nabeel; Jefferson, J. Ashley; Gipson, Patrick E.; Rizk, Dana V.; Sedor, John R.; Simon, James F.; McCarthy, Ellen T.; Brenchley, Paul; Sethi, Sanjeev; Ávila-Casado, Carmen; Beanlands, Heather; Lieske, John C.; Philibert, David; Li, Tingting; Thomas, Lesley F.; Green, Dolly F.; Juncos, Luis A.; Beara-Lasić, Lada; Blumenthal, Samuel S.; Sussman, Amy; Erickson, Stephen B.; Hladunewich, Michelle A.; Canetta, Pietro A.; Hebert, Lee A.; Leung, Nelson; Radhakrishnan, Jay; Reich, Heather N.; Parikh, Samir; Gipson, Debbie S.; Lee, Dominic K.; Costa, Bruno R. da; Jüni, Peter; Cattran, Daniel C.

doi:10.1056/nejmoa1814427

Cited by 399 publications

(390 citation statements)

References 32 publications

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“…In the CsA arm, if proteinuria was reduced (at least 25%), treatment was continued for an additional 6 months, then tapered, and discontinued after 2 months. It is important to emphasize that at month 12, there were no significant differences between both treatment arms regarding the number of responses (60% vs. 52%) [18] and that the poor results in the CsA arm were most likely due to the rapid discontinuation of the drug, contravening previously agreed recommendations [76]. Noteworthy, none of the patients in the RTX arm had complete remission at 6 months; therefore, all patients with significant reduction of proteinuria were re-treated [18].…”

Section: Treatment: a Holistic Approachmentioning

confidence: 91%

“…It is important to emphasize that at month 12, there were no significant differences between both treatment arms regarding the number of responses (60% vs. 52%) [18] and that the poor results in the CsA arm were most likely due to the rapid discontinuation of the drug, contravening previously agreed recommendations [76]. Noteworthy, none of the patients in the RTX arm had complete remission at 6 months; therefore, all patients with significant reduction of proteinuria were re-treated [18]. One important consideration is that RTX is lost in the urine in patients with NS compared to non-proteinuric subjects [77].…”

Section: Treatment: a Holistic Approachmentioning

confidence: 91%

“…Previous studies have reported complete or partial remission rates in about 60-65% of cases, with a median time to remission of approximately 7 months [20,30,72]. In a recent prospective randomized trial, the MENTOR investigators reported that RTX was superior to CsA in maintaining proteinuria remission in patients with MN and high risk of progression [18]. After 24 months, 60% of patients in the RTX group versus 20% in the CsA group had complete or partial remission.…”

Section: Treatment: a Holistic Approachmentioning

confidence: 99%

“…Prognosis is variable, with approximately 30% of affected patients reaching spontaneous remission (SR), one-third remaining stable, and one-third presenting with persistent NS [15,16]. In those who continue to have NS, ESRD may develop in about half of patients over a 10-year period [17,18].…”

Section: Introductionmentioning

confidence: 99%

“…In fact, the aforementioned study was published long before the description of anti-PLA2R1 antibodies, leading the way for the rationale of anti-CD20 antibody treatment even in subjects without evidence of nephritogenic autoantibodies. Moreover, in recent years, prospective clinical trials have demonstrated a beneficial role of RTX in patients with MN and nephrotic-range proteinuria [18,20]. Beyond a one-sizefits-all approach, it seems that at the present time, a personalized therapy should be applied based on antibody titers and clinical evolution.…”

Section: Introductionmentioning

confidence: 99%

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New Ways of Understanding Membranous Nephropathy

Trujillo

Alonso

Praga

2020

Nephron

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Background: In the last decade, great advances have been made in the field of membranous nephropathy (MN). The autoimmune nature of the disease has been confirmed with the description of diverse antigens, and few but very important prospective trials regarding treatment alternatives have been published, changing profoundly the way we understand this entity. Nowadays, an individualized therapeutic scheme based on clinical and serologic data appears to be the most appropriate method to manage patients with MN. Although there is still a long way to go, it is expected that future scientific progress will enable a patient-centered medicine based on concept-driven therapies. Summary: MN is the most common cause of nephrotic syndrome (NS) in white adults. Approximately one-third of patients achieve spontaneous remission, one-third remain stable, and onethird have an aggressive course with persistent NS and deterioration of renal function. About 80% of patients have circulating autoantibodies to phospholipase A2 receptor 1. Numerous therapies have been described including alkylating agents, rituximab, and calcineurin inhibitors, but new drugs are currently being explored. Here, we review the most important aspects regarding MN with an emphasis on results of the most recent clinical trials and pathophysiologic advances. Key Messages: 1. Evolving pathophysiologic concepts and recently published clinical trials have deeply changed our view of MN. 2. Most patients with MN present autoantibodies against diverse glomerular antigens. 3. Currently, an individual patient-centered management based on clinical and serologic markers is the most adequate approach to treat patients with MN.

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Section: Treatment: a Holistic Approachmentioning

confidence: 91%

Section: Treatment: a Holistic Approachmentioning

confidence: 91%

Section: Treatment: a Holistic Approachmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

New Ways of Understanding Membranous Nephropathy

Trujillo

Alonso

Praga

2020

Nephron

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Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome

Groote

Williams

et al. 2021

Cochrane Database of Systematic Reviews

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Monoclonal gammopathy of renal significance (MGRS): Real‐world data on outcomes and prognostic factors

et al. 2022

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Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis‐related to MGRS (MGRS‐A) was present in 180 patients; nonamyloidosis MGRS (MGRS‐NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0–121.0). Patients with MGRS‐A had a shorter overall survival than patients with MGRS‐NA (HR = 0.41, 95%CI: 0.25–0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04–115.96; p < 0.0001), one‐fourth of patients with ≥VGPR were renal nonresponders. In MGRS‐A, factors associated with poor prognosis included elevated levels of creatinine, beta‐2‐microglobulin, and hemodialysis at diagnosis. In MGRS‐NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.

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Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy

Cited by 399 publications

References 32 publications

New Ways of Understanding Membranous Nephropathy

New Ways of Understanding Membranous Nephropathy

Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome

Monoclonal gammopathy of renal significance (MGRS): Real‐world data on outcomes and prognostic factors

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