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Grant support

Research by the authors was supported by FIS/Fondos FEDER (PI18/01366, PI19/00588, PI19/00815, DTS18/00032, ERAPerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Espanola de Nefrologia, Fundacion Renal Inigo Alvarez de Toledo (FRIAT), and Comunidad de Madrid en Biomedicina B2017/BMD3686 CIFRA2-CM.

Analysis of institutional authors

Ortiz, AAuthor

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January 3, 2022
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Review

Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy

Publicated to:DRUGS. 82 (2): 109-132 - 2022-02-01 82(2), DOI: 10.1007/s40265-021-01656-1

Authors: Rojas-Rivera, Jorge; Fervenza, Fernando C.; Ortiz, Alberto;

Affiliations

Autonomous Univ Madrid, Ave Reyes Catolicos 2, Madrid 28040, Spain - Author
Hosp Univ Fdn Jimenez Diaz, IIS Fdn Jimenez Diaz, Div Nephrol & Hypertens, Ave Reyes Catolicos 2, Madrid 28040, Spain - Author
Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA - Author

Abstract

Immunosuppressive therapy is mandatory for primary membranous nephropathy with persistent nephrotic proteinuria or anti-phospholipase A2 receptor antibodies, reduced kidney function, or another risk factor for progression. Rituximab has demonstrated efficacy for proteinuria remission compared with renin-angiotensin system blockade or cyclosporine in two well-powered randomized controlled trials. More recently, STARMEN showed that alternating glucocorticoid-cyclophosphamide is superior to sequential tacrolimus-rituximab for proteinuria remission, although it was associated with a higher risk of non-serious adverse events. However, sequential tacrolimus-rituximab involved delayed lower dose rituximab and was the worst-performing rituximab regimen among those tested in randomized clinical trials. The RI-CYCLO pilot study did not demonstrate superiority of glucocorticoid-cyclophosphamide over rituximab and found no difference in adverse events. Overall, STARMEN and RI-CYCLO confirmed the efficacy of glucocorticoid-cyclophosphamide in patients with high-risk membranous nephropathy and the role of rituximab as a valid alternative. However, none of the trials tested an optimized rituximab protocol involving a second rituximab cycle before declaring treatment failure. Calcineurin inhibitors should be considered third-line drugs and sequential use of calcineurin inhibitor rituximab did not add over rituximab-only regimens. We critically review recent randomized controlled trials, propose a research agenda, and call for multinational pragmatic trials that enroll patients at referral centers to address unmet research needs.

Keywords

CorticosteroidsCyclosporineFollow-upMethylprednisoloneNephrotic syndromePlus cyclophosphamideRandomized-trialRituximab therapySteroidsTacrolimus monotherapy

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal DRUGS due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 2/94, thus managing to position itself as a Q1 (Primer Cuartil), in the category Toxicology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 2.2. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 2.89 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 6.41 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-22, the following number of citations:

  • WoS: 8
  • Scopus: 11
  • Europe PMC: 9

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-22:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 22.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 22 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 12.15.
  • The number of mentions on the social network X (formerly Twitter): 9 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/708060

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Rojas-Rivera, J) and Last Author (ORTIZ ARDUAN, ALBERTO).

the author responsible for correspondence tasks has been Rojas-Rivera, J.