Evidence map›Paper›PMID 40548378›Full record

Trial reportJCI insight2025

The distal nephron biomarkers associate with diabetic kidney disease progression.

Christina L Tamargo, Steven G Coca, Heather Thiessen Philbrook, David G Hu, Joachim H Ix, Michael G Shlipak, Linda F Fried, Orlando M Gutierrez, Sushrut S Waikar, Sarah J Schrauben and 9 more

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00555217 (CSP #565 - Combination Angiotensin Receptor Blocker and Angiotensin Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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.

NCT00555217 phase3terminatednot on this map

CSP #565 - Combination Angiotensin Receptor Blocker and Angiotensin Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy (VA NEPHRON-D Study)

TypeinterventionalSponsorUS Department of Veterans AffairsRan2008 to 2014Enrolled1,448ConditionsKidney Disease, Nephropathy, Type 2 DiabetesArmslosartan, lisinopril
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Observational
  4. Review
  5. Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026
    Review
  6. Article
  7. 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

19 authors.

Christina L TamargoDivision of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Steven G CocaBarbara T. Murphy Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Heather Thiessen PhilbrookDivision of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
David G HuDivision of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Joachim H IxDivision of Nephrology-Hypertension, Department of Medicine, UCSD, San Diego, California, USA.
Michael G ShlipakDepartment of Medicine, UCSF, San Francisco, California, USA.
Linda F FriedRenal Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
Orlando M GutierrezDepartment of Medicine and.
Sushrut S WaikarSection of Nephrology, Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Sarah J SchraubenDepartment of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jeffrey R SchellingDepartment of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Peter GanzDepartment of Medicine, UCSF, San Francisco, California, USA.
Paul L KimmelNational Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA.
Jason H GreenbergSection of Pediatric Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA.
Rajat DeoDivision of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ayumi TakakuraDivision of Renal Medicine and Engineering in Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Ramachandran S VasanThe University of Texas School of Public Health San Antonio, San Antonio, Texas, USA.
Joseph V BonventreDivision of Renal Medicine and Engineering in Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Chirag R ParikhDivision of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Funding

University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Kirk Michael Habegger · 2013 to 2026
$19.5M
Novel Kidney Injury Tools in Deceased Organ Donation to Predict Graft OutcomesR01DK093770 · NIDDK · YALE UNIVERSITY · PI Chirag R Parikh · 2012 to 2026
$9.5M
KIDNEY INJURY MOLECULE-1 IN EPITHELIAL REPAIRR01DK072381 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 2005 to 2025
$8.6M
Mechanisms of Ischemic Kidney Injury and RepairR01DK039773 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JOSEPH VINCENT BONVENTRE · 1987 to 2026
$6.2M
Chronic Kidney Disease (CKD) Biomarkers Consortium Data Coordinating CenterU01DK103225 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SCHRAUBEN, SARAH JEANNE · 2014 to 2020
$5.5M
Mechanisms of Ischemic Kidney Injury and RepairR37DK039773 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 1993 to 2021
$5.2M
Post-Discharge Nephrology Follow-up for Improved OutcomesU01DK129984 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI Chirag R Parikh · 2021 to 2026
$4.2M
AKI Matched Phenotype Linked Evaluation with Tissue (AMPLE-Tissue)U01DK114866 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI Chirag R Parikh · 2022 to 2026
$2.6M
Clinical effectiveness of a wearable hydration deviceR42AG080886 · NIA · TRITONX INC. · PI JOHNSON, EAMON, PIKTEL, JOSEPH · 2022 to 2025
$2.0M
Beyond the Glomerulus: Novel Clinical Markers of Kidney Health and PrognosisU01DK102730 · NIDDK · TUFTS MEDICAL CENTER · PI GUTIERREZ, ORLANDO M, IX, JOACHIM H · 2016 to 2020
$1.9M
Identification of CKD and CVD BiomarkersU01DK106965 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI BRUNENGRABER, HENRI, HOSTETTER, THOMAS HEARD · 2015 to 2019
$1.6M
Physical Function in Chronic Kidney Disease: Characterizing the Natural History and Relationship to Clinical OutcomesR01DK137087 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Sarah Jeanne Schrauben · 2023 to 2026
$1.3M
NIA NIH HHS R42 AG080886NIDDK NIH HHS K23 DK118198NIDDK NIH HHS P30 DK079626NIDDK NIH HHS R01 DK039773NIDDK NIH HHS R01 DK072381NIDDK NIH HHS R01 DK093770NIDDK NIH HHS R01 DK137087NIDDK NIH HHS R37 DK039773NIDDK NIH HHS U01 DK102730NIDDK NIH HHS U01 DK103225NIDDK NIH HHS U01 DK106962NIDDK NIH HHS U01 DK106965NIDDK NIH HHS U01 DK114866NIDDK NIH HHS U01 DK129984
6 · The paper itself

Abstract

BACKGROUNDWhile urinary biomarkers show promise in predicting diabetic kidney disease (DKD) progression, distal tubular markers remain understudied. We investigated the association of distal tubule markers, epidermal growth factor (EGF) and uromodulin (UMOD), with DKD progression in the Veterans Affairs Diabetes in Nephropathy (VA NEPHRON-D) clinical trial.

methodsWe used Cox regression models to evaluate the association between each biomarker and DKD progression and the relationship between change over time in biomarker and DKD progression. We used mixed models to investigate biomarker levels at baseline, 12 months, and over time and their relationships with longitudinal eGFR change.

resultsParticipants (n = 1,116) had type 2 diabetes, urine albumin-to-creatinine ratio (UACR) ≥ 300 mg/g, and eGFR 30-89.9 mL/min/1.73 m2. Mean age was 65 years, mean eGFR was 56 (SD 19) mL/min/1.73 m2, and median UACR was 840 (IQR 424-1,780) mg/g. One hundred forty-four participants (13%) had DKD progression over a median follow-up of 2.2 (1.3-3.1) years. Higher baseline EGF and UMOD were independently associated with a lower risk of DKD progression (adjusted HR 0.68, 95% CI 0.47, 0.99 and 0.85, [0.75, 0.98] per 2-fold higher concentration of EGF and UMOD, respectively). Serial biomarker measurements were performed at baseline and 12 months, and a slower decline in biomarkers was associated with a lower risk of DKD progression when adjusted for baseline biomarker levels.

conclusionUrinary EGF and UMOD may serve as valuable prognostic biomarkers in DKD.

trial registrationCLINICALTRIALS: gov NCT00555217.

fundingNIH U01DK102730, U01DK103225, K23 DK118198, R01DK137087, U01DK103225, R37DK039773, U01DK114866, U01DK106962, U01DK129984, and R01DK093770; National Institute of Diabetes and Digestive and Kidney Diseases contract U01DK106965.

Indexed as

Diabetes Mellitus, Type 2Diabetic NephropathiesEpidermal Growth FactorNephronsUromodulinAgedAlbuminuriaBiomarkersDisease ProgressionFemaleGlomerular Filtration RateHumansMaleMiddle AgedBiomarkersEpidermal Growth FactorUMOD protein, humanUromodulinChronic kidney diseaseClinical ResearchDiabetesNephrology

Identifiers

PMID40548378
PMCPMC12220953

What Socratic 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 Socratic graph.