Evidence mapPaperPMID 40842026Full record

ArticleJournal of translational medicine2025

In silico prediction of optimal multifactorial intervention in chronic kidney disease.

Agnieszka Latosinska, Ioanna K Mina, Thi Minh Nghia Nguyen, Igor Golovko, Felix Keller, Gert Mayer, Peter Rossing, Jan A Staessen, Christian Delles, Joachim Beige and 12 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Circulating and Urinary CCL20 in Human Kidney Disease.International journal of molecular sciences · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Agnieszka LatosinskaMosaiques Diagnostics GmbH, Rotenburger Straße 20, 30659, Hannover, Germany.
Ioanna K MinaMosaiques Diagnostics GmbH, Rotenburger Straße 20, 30659, Hannover, Germany.
Thi Minh Nghia NguyenMosaiques Diagnostics GmbH, Rotenburger Straße 20, 30659, Hannover, Germany.
Igor GolovkoMosaiques Diagnostics GmbH, Rotenburger Straße 20, 30659, Hannover, Germany.
Felix KellerDepartment of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria.
Gert MayerDepartment of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria.
Peter RossingSteno Diabetes Center Copenhagen, Herlev, Denmark.
Jan A StaessenNon-Profit Research Institute Alliance for the Promotion of Preventive Medicine, Mechlin, Belgium.
Christian DellesSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Joachim BeigeDivision of Nephrology and KfH Renal Unit, Hospital St Georg, Leipzig, Germany.
Griet GlorieuxDepartment of Internal Medicine and Paediatrics, Nephrology Section, Ghent University Hospital, Ghent, Belgium.
Andrew L ClarkHull and East Yorkshire NHS Hospitals Trust, Castle Hill Hospital, Cottingham, UK.
Joost P SchanstraInstitute of Cardiovascular and Metabolic Disease, Institut National de La Santé Et de La Recherche Médicale (INSERM), U1297, Toulouse, France.
Antonia VlahouCentre of Systems Biology, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Karlheinz PeterAtherothrombosis and Vascular Biology Program, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Ivan RychlíkDepartment of Internal Medicine, Third Faculty of Medicine, Charles University, and University Hospital Královské Vinohrady, Prague, Czech Republic.
Alberto OrtizInstituto de Investigación Sanitaria de La Fundación Jiménez Díaz (IIS-FJD) UAM, Madrid, Spain.
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Harald RupprechtDepartment of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH, Bayreuth, Germany.
Frederik PerssonDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Harald MischakMosaiques Diagnostics GmbH, Rotenburger Straße 20, 30659, Hannover, Germany. mischak@mosaiques-diagnostics.com.ORCID 0000-0003-0323-0306
Justyna SiwyMosaiques Diagnostics GmbH, Rotenburger Straße 20, 30659, Hannover, Germany.

Funding

Agence Nationale de la Recherche ANR-22-PERM-0002-06Austrian Science Fund Grant-DOI 10.55776/I6464Austrian Science Fund I 6464Bundesministerium für Bildung und Forschung 01EK2105ABundesministerium für Bildung und Forschung 01EK2105BBundesministerium für Bildung und Forschung 01EK2105CBundesministerium für Bildung und Forschung 01KU2307Bundesministerium für Wirtschaft und Klimaschutz ZIMKK5560002AP3Comunidad de Madrid en Biomedicina CIFRACOR-CMComunidad de Madrid en Biomedicina P2022/BMD-7223European Cooperation in Science and Technology CA21165European Health and Digital Executive Agency 101101220FIS/Fondos FEDER AC22/00027Horizon 2020 Framework Programme 848011HORIZON EUROPE Marie Sklodowska- Curie Actions 101072828HORIZON EUROPE Marie Sklodowska-Curie Actions 101072828HORIZON EUROPE Marie Sklodowska-Curie Actions 101168626Instituto de Salud Carlos III RICORS program to RICORS2040 (RD21/0005/0001)Instituto de Salud Carlos III SPACKDc PMP21/00109
6 · The paper itself

Abstract

backgroundChronic kidney disease (CKD) contributes to global morbidity and mortality. Early, targeted intervention can help mitigate its impact. CK273 is a urinary peptide classifier previously validated in a prospective clinical trial for the early detection of nephropathy. We hypothesized that drug-induced molecular changes in the urinary peptidome could be predicted in silico and guide selecting interventions for individual patients.

methodsThe efficacy of the urinary peptidomic classifier CKD273 in predicting major adverse kidney events (≥ 40% decline in estimated glomerular filtration rate or kidney failure -median follow-up: 1.50 (95%CI 0.35, 5.0) years), was confirmed in a retrospective cohort of 935 participants. In silico prediction of treatment effects from four drug-based interventions (Mineralocorticoid receptor antagonist, Sodium-glucose co-transporter 2 inhibitor, Glucagon-like peptide-1 receptor agonist, and Angiotensin receptor blocker), dietary intervention (olive oil), and exercise was performed based on: a) individual baseline urinary peptide profiles, and b) previously defined fold changes in peptide abundance after treatment in clinical trials. Following recalibration to align with outcomes of these trials, CKD273 scores were calculated for each patient after in silico treatment. For combination treatments, the effects of multiple interventions were combined.

resultsSimulated interventions demonstrated a significant reduction in median CKD273 scores, from 0.57 (IQR: 0.19-0.81) before to 0.039 (IQR: -0.192-0.363) after the most beneficial intervention (paired Wilcoxon test, P < 0.0001). The combination of all available treatments was not the most frequently predicted optimal intervention. Patients with higher baseline CKD273 scores required more complex intervention combinations to achieve the greatest score reduction.

conclusionsThis study supports the feasibility of in silico predicting effects of therapeutic interventions on CKD progression. By identifying the most beneficial treatment combinations for individual patients, this approach paves the way for precision medicine trials in CKD. A prospective study is currently being planned to validate the in silico-guided intervention approach and determine its exact benefits on patient-relevant outcomes.

Indexed as

Computer SimulationRenal Insufficiency, ChronicAgedFemaleHumansMaleMiddle AgedPeptidesPeptidesChronic kidney diseaseClinical proteomicsDrug response predictionOptimizing interventionUrine peptides

Identifiers

PMID40842026
PMCPMC12372250

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.