Evidence map›Paper›PMID 39435665›Full record

ArticleJCI insight2024

Circulating proteins linked to apoptosis processes and fast development of end-stage kidney disease in diabetes.

Katsuhito Ihara, Eiichiro Satake, Parker C Wilson, Bozena Krolewski, Hiroki Kobayashi, Zaipul I Md Dom, Joseph Ricca, Jonathan Wilson, Jonathan M Dreyfuss, Monika A Niewczas and 6 more

Abstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. 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

16 authors.

Katsuhito IharaResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Eiichiro SatakeResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Parker C WilsonDepartment of Pathology and Immunology, Washington University in St. Louis, St. Louis, Missouri, USA.
Bozena KrolewskiResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Hiroki KobayashiResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Zaipul I Md DomResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Joseph RiccaResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Jonathan WilsonDiabetes and Complication Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Jonathan M DreyfussResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Monika A NiewczasResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Alessandro DoriaResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Robert G NelsonResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Marcus G PezzolesiDivision of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Benjamin D HumphreysDivision of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
Kevin DuffinDiabetes and Complication Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Andrzej S KrolewskiResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA.

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Tumor necrosis factor superfamily of ligands and receptors in progressive renal decline in diabetesR01DK041526 · NIDDK · JOSLIN DIABETES CENTER · PI KROLEWSKI, ANDRZEJ S · 1990 to 2018
$7.8M
Causal connections between axon guidance proteins and early progressive kidney function decline in diabetesR01DK131061 · NIDDK · JOSLIN DIABETES CENTER · PI KROLEWSKI, ANDRZEJ S · 2022 to 2025
$2.7M
Development of Prognostic Algorithms to Identify Subjects at High Risk of ESKD in Type 2 DiabetesR01DK126799 · NIDDK · JOSLIN DIABETES CENTER · PI KROLEWSKI, ANDRZEJ S · 2021 to 2024
$2.7M
Understanding the role of the Complement Proteome in progressive Diabetic Kidney DiseaseR01DK123459 · NIDDK · JOSLIN DIABETES CENTER · PI NIEWCZAS, MONIKA ANNA · 2020 to 2024
$2.3M
The role of microRNAs in progressive renal decline in Type 1 diabetesR01DK110350 · NIDDK · UNIVERSITY OF UTAH · PI PEZZOLESI, MARCUS GUY · 2017 to 2021
$1.8M
Proteomic Biomarkers Prognostic for Diabetic Wound HealingR33DK131915 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI NIEWCZAS, MONIKA ANNA, VEVES, ARISTIDIS · 2024 to 2025
$1.1M
Proteomic Biomarkers Prognostic for Diabetic Wound HealingR61DK131915 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI NIEWCZAS, MONIKA ANNA, VEVES, ARISTIDIS · 2022 to 2023
$1.1M
The Single Cell Landscape of Early Human Diabetic NephropathyK08DK126847 · NIDDK · WASHINGTON UNIVERSITY · PI Parker C. Wilson · 2022 to 2026
$840k
NIDDK NIH HHS K08 DK126847NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK041526NIDDK NIH HHS R01 DK110350NIDDK NIH HHS R01 DK123459NIDDK NIH HHS R01 DK126799NIDDK NIH HHS R01 DK131061NIDDK NIH HHS R33 DK131915NIDDK NIH HHS R61 DK131915
6 · The paper itself

Abstract

Many circulating proteins are associated with risk of ESKD, but their source and the biological pathways/disease processes they represent are unclear. Using OLINK proteomics platform, concentrations of 455 proteins were measured in plasma specimens obtained at baseline from 399 individuals with diabetes. Elevated concentrations of 46 circulating proteins were associated (P < 1 × 10-5) with development of ESKD (n = 143) during 7-15 years of follow-up. Twenty of these proteins enriched apoptosis/TNF receptor signaling pathways. A subset of 20 proteins (5-7 proteins), summarized as an apoptosis score, together with clinical variables accurately predicted risk of ESKD. Expression of genes encoding the 46 proteins in peripheral WBCs showed no difference between cells from individuals who did or did not develop ESKD. In contrast, plasma concentration of many of the 46 proteins differed by this outcome. In single-nucleus RNA-Seq analysis of kidney biopsies, the majority of genes encoding for the 20 apoptosis/TNF receptor proteins were overexpressed in injured versus healthy proximal tubule cells. Expression of these 20 genes also correlated with the overall index of apoptosis in these cells. Elevated levels of circulating proteins flagging apoptotic processes/TNF receptor signaling pathways - and likely originating from kidney cells, including injured/apoptotic proximal tubular cells - preceded the development of ESKD.

Indexed as

ApoptosisKidney Failure, ChronicAdultAgedBiomarkersBlood ProteinsDiabetic NephropathiesFemaleHumansMaleMiddle AgedProteomicsSignal TransductionBiomarkersBlood ProteinsApoptosisDiabetesNephrology

Identifiers

PMID39435665
PMCPMC11529980

What Socratic holds

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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.