Evidence mapPaperPMID 41745778Full record

ReviewToxins2026

Uremic Toxin-Driven Vascular Calcification in Chronic Kidney Disease: Molecular Pathways and Integrated Phenotypes.

Rodolfo Fernando Rivera, Maria Teresa Sciarrone Alibrandi, Nadia Edvige Foligno, Lorenza Magagnoli, Paola Ciceri, Mario Cozzolino

Abstract readReview
In one paragraph

Review in Toxins, 2026. 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. Review
  2. Review
  3. Review
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

6 authors.

Rodolfo Fernando RiveraNephrology and Dialysis Unit, Pio XI Hospital ASST-Brianza, 20832 Desio, Italy.ORCID 0000-0002-5456-6785
Maria Teresa Sciarrone AlibrandiNephrology and Dialysis Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.ORCID 0000-0001-6322-0818
Nadia Edvige FolignoNephrology and Dialysis Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.ORCID 0000-0001-9536-9254
Lorenza MagagnoliNephrology and Dialysis, Department of Health Sciences, University of Milan, 20142 Milan, Italy.ORCID 0000-0003-2853-1332
Paola CiceriNephrology and Dialysis, Department of Health Sciences, University of Milan, 20142 Milan, Italy.
Mario CozzolinoNephrology and Dialysis, Department of Health Sciences, University of Milan, 20142 Milan, Italy.ORCID 0000-0002-8494-6252

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundVascular calcification (VC) affects up to 90% of patients with end-stage renal disease and increases cardiovascular mortality 3- to 5-fold. Once considered passive mineral deposition, VC is now recognized as an active, toxin-driven process orchestrating vascular smooth muscle cell transdifferentiation, endothelial dysfunction, and matrix remodeling. However, current uremic toxin classifications remain biochemically oriented, providing limited clinical guidance for risk stratification and therapeutic selection.

methodsThis comprehensive review reframes uremic toxin-driven VC through an integrated phenotypic lens, synthesizing molecular mechanisms, clinical biomarkers, and therapeutic targets into a unified translational framework.

resultsWe propose five mechanistic-clinical phenotypes representing distinct biological trajectories of vascular injury. These include (1) inflammatory-oxidative (dominated by indoxyl sulfate, p-cresyl sulfate, NLRP3 inflammasome activation), (2) mineral-metabolic (hyperphosphatemia, FGF23 excess, Klotho deficiency), (3) epigenetic-senescent (histone modifications, microRNA dysregulation, cellular senescence), (4) endocrine cross-talk (vitamin D, PTH, gut-derived metabolites), and (5) integrated toxic continuum (convergence of multiple pathways in advanced disease). A comprehensive biomarker panel spanning inflammatory markers, mineral metabolism parameters, epigenetic indicators, and endocrine-gut metabolites enables phenotypic stratification and therapeutic monitoring. Emerging therapies-including tissue-nonspecific alkaline phosphatase inhibition, ectonucleotide pyrophosphatase/phosphodiesterase 1 enzyme replacement, vitamin K

conclusionsThis phenotype-oriented paradigm transforms VC from an inevitable complication into a targetable and potentially reversible manifestation of uremic toxicity, establishing a translational foundation for precision-based vascular medicine in chronic kidney disease. The framework enables biomarker-guided patient stratification, rational therapeutic selection, and phenotype-enriched clinical trial design.

Indexed as

Renal Insufficiency, ChronicUremic ToxinsVascular CalcificationAnimalsBiomarkersFibroblast Growth Factor-23HumansPhenotypeBiomarkersFGF23 protein, humanFibroblast Growth Factor-23Uremic Toxinschronic kidney diseaseindoxyl sulfatephenotypic clustersprecision medicinetherapeutic targetsuremic toxinsvascular calcification

Identifiers

PMID41745778
PMCPMC12944978

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.