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Grant support

This work was supported by grants from Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119, PI20/00140, DTS20/00083, PI18/01366, PI19/00588, PI19/00815, DTS18/00032, Red de Investigacion Renal REDINREN: RD16/0009, RICORS2040 RD21/0005/0001) Comunidad Autonoma de Madrid FEDER-a way to build Europe (B2017/BMD-3751 NOVELREN-CM to MR-O and SL) ; Convocatoria Dinamizacion Europa Investigacion 2019" MINECO (EIN2019-10329 4 to M.R-O B2017/BMD-368 6 CIFRA2-CM to AO) ; Innovation programme under the Marie Skodowska-Curie grant of the European Union's Horizon 2020 (IMPROVE-PD ID: 812699) to MR-O; and ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, Sociedad Espanola de Nefrologia, FRIAT, Comunidad de Madrid en Biomedicina and Ministerio de Ciencia e Innovacion: PID2019-104233RB-I00/AEI/10.13039/501100011033 to SL.

Analysis of institutional authors

Ruiz-Ortega MAuthorOrtiz ACorresponding Author

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March 9, 2022
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Review

Antifibrotic Agents for the Management of CKD: A Review

Publicated to:AMERICAN JOURNAL OF KIDNEY DISEASES. 80 (2): 251-263 - 2022-08-01 80(2), DOI: 10.1053/j.ajkd.2021.11.010

Authors: Ruiz-Ortega M, Lamas S, Ortiz A

Affiliations

Ctr Biol Mol Severo Ochoa, Program Physiol & Pathol Proc, Madrid, Spain - Author
Program of Physiological and Pathological Processes, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), 28049, Madrid, Spain. - Author
Red Invest Renal, Madrid, Spain - Author
Univ Autonoma Madrid, Fdn Jimenez Diaz, IIS, Nephrologyand Hypertens, Av Reyes Catolicos 2, Madrid 28040, Spain - Author
Univ Autonoma Madrid, Fdn Jimenez Diaz, Inst Invest Sanitaria, Nephrol & Hypertens, Madrid, Spain - Author
Univ Autonoma Madrid, Fdn Jimenez Diaz, Mol & Cellular Biol Renal & Vasc Pathol, Inst Invest Sanitaria, Madrid, Spain - Author
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Abstract

Kidney fibrosis is a hallmark of chronic kidney disease (CKD) and a potential therapeutic target. However, there are conceptual and practical challenges to directly targeting kidney fibrosis. Whether fibrosis is mainly a cause or a consequence of CKD progression has been disputed. It is unclear whether specifically targeting fibrosis is feasible in clinical practice as most drugs that decrease fibrosis in preclinical models also target additional and often multiple pathogenic pathways (e.g. renin-angiotensin-aldosterone system blockade). Finally, tools to assess whole kidney fibrosis in routine clinical practice are lacking. Pirfenidone, a drug used for idiopathic pulmonary fibrosis (IPF), is undergoing a phase 2 trial for kidney fibrosis. Other drugs in use or being tested for IPF (e.g. nintedanib, PRM-151, epigallocatechin gallate) are also potential candidates to treat kidney fibrosis. Novel therapeutic approaches may include antagomirs (e.g. lademirsen) or drugs targeting IL-11 or NKD2. Reversing dysfunctional tubular cell metabolism that leads to kidney fibrosis offers additional therapeutic opportunities. However, any future drug targeting fibrosis of the kidneys should demonstrate added benefit to a novel standard of care combining renin-angiotensin system with mineralocorticoid receptor (e.g. finerenone) blockade or with SGLT2 inhibitors.Copyright © 2022. Published by Elsevier Inc.

Keywords

diabetic-nephropathyfailurefibrosisfresolimumabhealthmortalitypirfenidoneprogressionprotectsAdaptor proteins, signal transducingAntifibrotic agentAntifibrotic agentsBg00011Brain natriuretic peptideCalcium binding proteinCalcium-binding proteinsCanagliflozinCause of deathCell metabolismChronic kidney diseaseChronic kidney disease (ckd)Chronic kidney failureChronic kidney-diseaseClinical practiceComplicationDapagliflozinDisease exacerbationDrug candidateDrug mechanismDrug targetingEpigallocatechin gallateEplerenoneEstimated glomerular filtration rateFibromirFibrosing alveolitisFibrosisFinerenoneFresolimumabGcs 100GlomerulosclerosisGlomerulus filtration rateHumanHumansHypoxia inducible factorIdiopathic pulmonary fibrosisInterleukin 11Kidney fibrosisKidney polycystic diseaseLademirsenLife expectancyLy2382770Mineralocorticoid antagonistMineralocorticoid receptorMitochondriaMolecular imagingNintedanibNkd2 protein, humanNuclear magnetic resonance imagingPamrevlumabPentoxifyllinePhase 2 clinical trialPirfenidonePlaceboRenal insufficiency, chronicRenin angiotensin aldosterone systemRenin-angiotensin systemReviewSignal transducing adaptor proteinSignal transductionSpironolactoneTrametinibTreatmentVascular fibrosisWnt signalingX-ray computed tomographyZinpentraxin alfaZiritaxestat

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal AMERICAN JOURNAL OF KIDNEY DISEASES 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 6/88, thus managing to position itself as a Q1 (Primer Cuartil), in the category Urology & Nephrology. 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: 6.69. 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: 7.3 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 32.12 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-05, the following number of citations:

  • WoS: 20
  • Scopus: 27
  • Europe PMC: 19

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 2025-08-05:

  • 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: 87.
  • 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: 91 (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: 24.25.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 44 (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.

Leadership analysis of institutional authors

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 (RUIZ ORTEGA, MARTA) and Last Author (ORTIZ ARDUAN, ALBERTO).

the author responsible for correspondence tasks has been ORTIZ ARDUAN, ALBERTO.