Management of Membranous Nephropathy after MENTOR

Trivin-Avillach, Claire; Beck, Laurence H.

doi:10.2215/cjn.10240819

Cited by 10 publications

(13 citation statements)

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“…These comorbidities likely have an unfavorable influence on long-term kidney and patient health. Given these considerations, along with the relapse-free remission rates, 16 , 20 we advocate the use of CNIs as an adjunct therapy to other immunosuppression such as rituximab 21 for antiproteinuric-resistant PMN, as opposed to first-line single (or with GC) therapy.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Follow-Up of Cyclical Cyclophosphamide and Steroids Versus Tacrolimus and Steroids in Primary Membranous Nephropathy

Ramachandran

Kumar

Bharati

et al. 2021

Kidney International Reports

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Introduction Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommends cyclical cyclophosphamide plus glucocorticoids (GC) (modified Ponticelli regimen) or calcineurin inhibitors (CNIs) such as tacrolimus (TAC) or cyclosporine as the first-line agents for the management of primary membranous nephropathy (PMN) that is resistant to antiproteinuric therapy with renin-angiotensin system blockers. However, the long-term outcome of patients treated with CNIs is not known. Methods We report the outcomes of 70 patients randomized 1:1 to receive modified Ponticelli regimen or TAC/GC for renin-angiotensin system–resistant PMN who were prospectively followed for 6 years. Patients were followed monthly for 12 months, then quarterly for 12 months, and then every 6 months through the end of 6 years. Results At the end of 6 years, 21 (61.76%) and 9 (28.12%) patients maintained relapse-free remission in modified Ponticelli regimen and TAC/GC groups, respectively (relative risk [RR]: 2.19, 95% confidence interval [CI]: 1.23 to 4.15), and 30 (88.23%) and 17 (53.12%) patients were in remission (including relapses) in modified Ponticelli regimen and TAC/GC groups (RR: 1.66; 95% CI: 1.21 to 2.45), respectively. There was no significant difference in the proportion of patients who had a 40% decline in the estimated glomerular filtration rate (eGFR), death, or end-stage kidney disease between the groups. None of the patients treated with modified Ponticelli regimen reported a solid organ or hematological malignancy. Conclusions To conclude, in the long-term, modified Ponticelli regimen is superior to TAC/GC as first-line therapy for the management of antiproteinuric-resistant PMN.

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Section: Discussionmentioning

confidence: 99%

Long-Term Follow-Up of Cyclical Cyclophosphamide and Steroids Versus Tacrolimus and Steroids in Primary Membranous Nephropathy

Ramachandran

Kumar

Bharati

et al. 2021

Kidney International Reports

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“…Disease evolution is highly variable with spontaneous remission, persistent proteinuria or end-stage kidney diseases (ESKD) (12). Rituximab is a first line anti-CD20 immunosuppressive drug often used to treat MN patients which induces remission in about 35% to 67% of cases (13)(14)(15), while MN recurs after remission in about 20% of cases (14). Nephrotic syndrome has been correlated with an exceptionally high risk of venous thromboembolic events (16,17).…”

Section: Introductionmentioning

confidence: 99%

Th17-Immune Response in Patients With Membranous Nephropathy Is Associated With Thrombosis and Relapses

et al. 2020

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Membranous nephropathy (MN) is a rare autoimmune kidney disease. Most autoimmune diseases are associated with a pro-inflammatory Th17-immune response, but little is known about immune dysregulation in MN. In China, MN was associated with exposure to fine air particulate matter (PM2.5) that could act as a danger signal and redirect immune response toward the Th2 or Th17 pathway. We aimed to analyze the cytokine profile of MN patients and to study the possible environmental factors involved in this immune reorientation, as well as the consequences on the prognosis of the disease. In this prospective study, 59 MN patients filled a comprehensive lifestyle questionnaire. Peripheral blood cells from MN patients were stimulated in vitro to measure the cytokines produced in supernatant. Cytokine profiles of MN patients were compared to 28 healthy donors and analyzed regarding individual PM2.5 exposure. Compared to healthy donors, MN patients had higher serum levels of Th17 and Th2 cytokines IL-17A (62 pg/ml [IQR, 16–160] versus 31 [IQR, 13–51], P=0.035), IL-6 (66767 pg/ml [IQR, 36860–120978] versus 27979 [IQR, 18672–51499], P=0.001), and IL-4 (12 pg/ml [IQR, 0–33] versus 0 pg/ml [IQR, 0–0], P=0.0003), respectively, as well as a deficiency of Th1 and regulatory T cell cytokines IFN-γ (5320 pg/ml [IQR, 501–14325] versus 18037 [IQR, 4889–31329], P=0.0005) and IL-10 (778 pg/ml [IQR, 340–1247] versus 1102 [IQR, 737–1652], P=0.04), respectively. MN patients with high IL-17A levels lived in areas highly exposed to PM2.5: 51 μg/m3 versus 31 μg/m3 for patients with low IL-17A levels (P=0.002) while the World Health Organization recommends an exposition below 10 μg/m3. MN patients with Th17-mediated inflammation had more venous thromboembolic events (P=0.03) and relapsed more often (P=0.0006). Rituximab treatment induced Th1 and regulatory T cell cytokines but did not impact Th17 cytokines. MN patients with Th17-mediated inflammation which appears to be related to an urban environment have worse prognosis. Alternative strategies targeting dysregulated cytokine balance could be considered for these patients at high risk of relapse.

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“…The main strength of our study is the long follow-up period that allowed us to assess the influence of the therapeutic intervention on kidney survival. The slow-to-form, slower-toresolve immune deposits 33 suggest that remissions in membranous nephropathy may take years; hence, clinical trials limited to 24 months may not fully describe the true impact on kidney outcomes. We consider that studies based on "real world experience",…”

Section: Discussionmentioning

confidence: 99%

Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy

et al. 2020

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BackgroundOptimal immunosuppressive treatment for membranous nephropathy is still a matter of controversy. Current recommendations include oral cyclophosphamide combined with steroids (modified Ponticelli regimen) as first-line treatment in patients who are high risk. However, concerns about the cumulative toxicity of oral cyclophosphamide persist. In the last 30 years, a protocol based on low-dose intravenous cyclophosphamide plus steroids has been used to treat membranous nephropathy in Uruguay. We aimed to assess the efficacy of this regimen to induce clinical remission in patients with membranous nephropathy.MethodsIn this retrospective, observational cohort study, we analyzed the outcome of 55 patients with membranous nephropathy treated between 1990 and 2017 with a 6-month course of alternating steroids (months 1, 3, and 5) plus intravenous cyclophosphamide (single dose of 15 mg/kg on the first day of months 2, 4, and 6).ResultsAt 24 months, 39 (71%) patients achieved clinical response with complete remission observed in 23 patients (42%) and partial remission in 16 (29%). Median time to achieve partial and complete remission was 5.9 and 11.5 months, respectively. Absence of response was observed in 16 patients (29%), five of whom started chronic RRT after a median follow-up of 3.5 years. Clinical relapse occurred in nine of 33 (27%) patients at a median of 34 months after treatment discontinuation.ConclusionsReplacement of oral cyclophosphamide with a single intravenous pulse on months 2, 4, and 6 of the modified Ponticelli regimen can be an effective and safe alternative for treatment of membranous nephropathy.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_09_24_KID0002802020.mp3

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Management of Membranous Nephropathy after MENTOR

Cited by 10 publications

References 10 publications

Long-Term Follow-Up of Cyclical Cyclophosphamide and Steroids Versus Tacrolimus and Steroids in Primary Membranous Nephropathy

Long-Term Follow-Up of Cyclical Cyclophosphamide and Steroids Versus Tacrolimus and Steroids in Primary Membranous Nephropathy

Th17-Immune Response in Patients With Membranous Nephropathy Is Associated With Thrombosis and Relapses

Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy

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