Evidence map›Paper›PMID 41654492›Full record

Trial reportNature communications2026

Urinary clusterin as a biomarker of human kidney disease progression and response to the endothelin receptor antagonist atrasentan: An exploratory analysis from the SONAR trial.

Wenjun Ju, Viji Nair, Priya Vart, J David Smeijer, Kelly L Hudkins, Erik Moedt, Maria Larkina, Paul Perco, Frédéric Burdet, Kerby Shedden and 12 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01858532 (A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects With Type 2 Diabetes and Nephropathy. SONAR), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

NCT01858532 phase3terminatednot on this map

A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects With Type 2 Diabetes and Nephropathy. SONAR: Study Of Diabetic Nephropathy With Atrasentan

TypeinterventionalSponsorAbbVieRan2013 to 2018Enrolled5,107ConditionsDiabetic NephropathyArmsAtrasentan, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Novel protein biomarkers for risk stratification and personalized medicine.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Article
  2. 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.

Wenjun JuDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA. wenjunj@med.umich.edu.ORCID 0000-0002-9136-8454
Viji NairDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Priya VartDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
J David SmeijerDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Kelly L HudkinsDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Erik MoedtDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID 0009-0003-3983-5136
Maria LarkinaDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Paul PercoDepartment of Internal Medicine IV, Medical University Innsbruck, Innsbruck, Austria.ORCID 0000-0003-2087-5691
Frédéric BurdetVital-IT, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.ORCID 0000-0002-2923-827X
Kerby SheddenDepartment of Statistics, University of Michigan, Ann Arbor, MI, USA.
Michael HwangDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0002-5546-6812
Edmond LeeDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0009-2443-6638
Christopher O'ConnorDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
John HartmanDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Lalita SubramanianDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Markus BitzerDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3711-2984
Mark IbbersonVital-IT, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.ORCID 0000-0003-3152-5670
Kevin L DuffinEli Lilly and Company, Indianapolis, IN, USA.
Maria F GomezDiabetic Complications Unit, Department of Clinical Sciences, Lund University Diabetes Center, Malmö, Sweden.ORCID 0000-0001-6210-3142
Charles E AlpersDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-1859-1772
Matthias KretzlerDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA. kretzler@umich.edu.
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.j.lambers.heerspink@umcg.nl.ORCID 0000-0002-3126-3730

Funding

KPMP Kidney Mapping and Atlas Project (KMAP)U01DK133090 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jonathan Himmelfarb, Matthias Kretzler · 2022 to 2026
$10.4M
University of Michigan O'Brien Kidney Translational Resource Center (MKTC)U54DK137314 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Salim Hayek · 2023 to 2026
$4.7M
European Union’s HORIZON Research and InnovationGeorge M. O’Brien Michigan Kidney Translational Resource CenterInnovative Medicines InitiativeSwedish Foundation for Strategic ResearchSwedish Heart and Lung FoundationSwedish Research CouncilSwedish Strategic Research Area ExodiabU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) U01DK133090U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) U24-DK114886U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) U54-DK-083912U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) U54DK137314
6 · The paper itself

Abstract

The endothelin receptor antagonist atrasentan improved kidney outcomes in the SONAR trial for type 2 diabetes and chronic kidney disease (NCT01858532), though individual responses varied. To identify molecular biomarkers of atrasentan response and outcome, we conducted a nested case-control proteomics study (N = 180) within the SONAR trial population and identified urinary clusterin (uCLU) as the top candidate. Transcriptomic analyses of human kidney biopsies at tissue and single cell level from independent cohorts revealed higher CLU mRNA levels associated with worse kidney function and outcomes. An endothelin signaling activation score derived from pathway genes was reduced by atrasentan in mice with diabetic kidney disease. In the SONAR trial (N = 3,060) population, higher uCLU predicted worse outcomes, while atrasentan reduced uCLU by 42.6% over six weeks. Early uCLU changes independently predict improved kidney outcomes. In summary, uCLU is associated with kidney disease progression and response to atrasentan treatment, supporting its potential as a pharmacodynamic biomarker to target therapy.

Indexed as

AtrasentanClusterinDiabetic NephropathiesEndothelin Receptor AntagonistsRenal Insufficiency, ChronicAnimalsBiomarkersCase-Control StudiesDiabetes Mellitus, Type 2Disease ProgressionFemaleHumansKidneyMaleMiceMiddle AgedAtrasentanBiomarkersCLU protein, humanClusterinEndothelin Receptor Antagonists

Identifiers

PMID41654492
PMCPMC12993053

What OpenQuestion holds

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Registered trials

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 OpenQuestion graph.