Evidence map›Paper›PMID 38484321›Full record

ArticleDiabetes care2024

Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC.

Christine P Limonte, Xiaoyu Gao, Ionut Bebu, Jesse C Seegmiller, Amy B Karger, Gayle M Lorenzi, Mark Molitch, Harsha Karanchi, Bruce A Perkins, Ian H de Boer and 2 more

Open access · greenAbstract read
In one paragraph

Article in Diabetes care, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Multi-Omics Integration IdentifiesInternational journal of molecular sciences · 2025
    Article
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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

12 authors at 7 institutions in 2 countries.

Christine P LimonteDivision of Nephrology, Department of Medicine, University of Washington, Seattle, WA.ORCID 0000-0002-9162-7428
Xiaoyu GaoBiostatistics Center, The George Washington University, Rockville, MD.
Ionut BebuBiostatistics Center, The George Washington University, Rockville, MD.
Jesse C SeegmillerDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
Amy B KargerDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
Gayle M LorenziDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Mark MolitchNorthwestern University, Chicago, IL.ORCID 0000-0002-8492-3587
Harsha KaranchiDepartment of Medicine, Medical University of South Carolina, Charleston, SC.
Bruce A PerkinsDivision of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Ian H de BoerDivision of Nephrology, Department of Medicine, University of Washington, Seattle, WA.
DCCT
EDIC Research Group
George Washington University · USUniversity of Minnesota · USUniversity of Washington · USMedical University of South Carolina · USNorthwestern University · USUniversity of California San Diego · USUniversity of Toronto · CA

Funding

Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
Limited Competition for the Continuation of Epidemiology of Diabetes Interventions and Complications (EDIC) Study Clinical Research Center (Collaborative U01)U01DK094157 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI Ionut Bebu, Barbara Halina Braffett · 2011 to 2026
$97.6M
Disparities in COVID Disease Severity and Outcomes in New York CityUL1TR002384 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI JULIANNE L IMPERATO-MCGINLEY · 2017 to 2026
$86.2M
Epidemiology of Diabetes Interventions and Complications Data Coordinating CenterU01DK094176 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI BEBU, IONUT, BRAFFETT, BARBARA HALINA · 2012 to 2022
$30.8M
EYE MOVEMENT: PHYSIOLOGICAL ORGANIZATIONR01EY002007 · NEI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BAKER, ROBERT G · 1985 to 2014
$3.9M
Autophagy in Diabetic Kidney DiseaseK23DK135789 · NIDDK · UNIVERSITY OF WASHINGTON · PI Christine Limonte · 2023 to 2026
$753k
MOLECULAR GENETIC STUDIES OF UREA CYCLE DISORDERSK08DK001993 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI FINKELSTEIN, JANICE E · 1990 to 1990
–
Clinical Translational Science CenterDivision of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease 1982-1993NCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1 TR002384NIDDK NIH HHS K23 DK135789NIDDK NIH HHS U01 DK094157NIDDK NIH HHS U01 DK094176the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program 1993-2007
6 · The paper itself

Abstract

objectiveTubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D). RESEARCH DESIGN AND

methodsWe performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate [AER] ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.73 m2) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. Biomarkers included KIM-1 and sTNFR1 in serum/plasma, MCP-1 and EGF in urine, and a composite tubular secretion score reflecting secreted solute clearance. We assessed biomarkers using single values, as mean values from consecutive time points, and as change over consecutive time points, each as time-updated exposures.

resultsAt baseline, mean diabetes duration was 5.9 years, with mean HbA1c 8.9%, eGFR 125 mL/min/1.73 m2, and AER 16 mg/day. There were 4.8 and 3.5 cases per 1,000 person-years of macroalbuminuria and low eGFR, respectively. Assessed according to single biomarker values, KIM-1 was associated with risk of subsequent macroalbuminuria and low eGFR (hazard ratio [HR] per 20% higher biomarker 1.11 [95% CI 1.06, 1.16] and 1.12 [1.04, 1.21], respectively) and sTNFR1 was associated with subsequent macroalbuminuria (1.14 [1.03, 1.25]). Mean KIM-1 and EGF-to-MCP-1 ratio were associated with subsequent low eGFR. In slope analyses, increases in KIM-1 and sTNFR1 were associated with subsequent macroalbuminuria (per 20% biomarker increase, HR 1.81 [1.40, 2.34] and 1.95 [1.18, 3.21]) and low eGFR (2.26 [1.65, 3.09] and 2.94 [1.39, 6.23]).

conclusionsSerial KIM-1 and sTNFR1 are associated with incident macroalbuminuria and sustained low eGFR in T1D.

Indexed as

AlbuminuriaBiomarkersDiabetic NephropathiesGlomerular Filtration RateHepatitis A Virus Cellular Receptor 1AdultChemokine CCL2Diabetes Mellitus, Type 1FemaleHumansKidney TubulesMaleReceptors, Tumor Necrosis Factor, Type IYoung AdultBiomarkersChemokine CCL2HAVCR1 protein, humanHepatitis A Virus Cellular Receptor 1Receptors, Tumor Necrosis Factor, Type I

Identifiers

PMID38484321
PMCPMC11362110
OpenAlexW4392793556

What OpenQuestion holds

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Registered trials

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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.