Evidence map›Paper›PMID 34396789›Full record

ArticleAmerican journal of physiology. Renal physiology2021

Intrarenal modulation of NF-κB activity attenuates cardiac injury in a swine model of CKD: a renal-cardio axis.

Alejandro R Chade, Jason E Engel, Michael E Hall, Alfonso Eirin, Gene L Bidwell

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. When in doubt, pig it out: a versatile translational platform to study CKD, HFpEF, and CKM syndrome.American journal of physiology. Heart and circulatory physiology · 2025
    Review
  5. Article
  6. A minimally invasive swine model of chronic kidney disease-associated heart failure.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  7. Article
  8. Personalized Antifibrotic Therapy in CKD Progression.Journal of personalized medicine · 2024
    Review
  9. The role of PI3K/Akt signaling pathway in chronic kidney disease.International urology and nephrology · 2024
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Novel Drug Delivery Technologies and Targets for Renal Disease.Hypertension (Dallas, Tex. : 1979) · 2022
    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

5 authors at 2 institutions in 1 country.

Alejandro R ChadeDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.ORCID 0000-0002-3672-3409
Jason E EngelDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
Michael E HallDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.ORCID 0000-0002-5733-1025
Alfonso EirinDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Gene L BidwellDepartment of Neurology, University of Mississippi Medical Center, Jackson, Mississippi.ORCID 0000-0001-9104-150X
Jackson Memorial Hospital · USMayo Clinic · US

Funding

The role of leptin in autoimmune-associated hypertensionP20GM104357 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI TAYLOR, ERIN BASSFORD · 2013 to 2022
$23.4M
A Novel Protein Delivery System for Therapy of PreeclampsiaR01HL121527 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI BIDWELL, GENE LEFLORE · 2014 to 2023
$4.1M
Microcirculation in Renovascular HypertensionR01HL095638 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI CHADE, ALEJANDRO ROBERTO · 2010 to 2021
$3.9M
HHS | National Institutes of Health (NIH) P20GM104357NHLBI NIH HHS R01 HL095638NHLBI NIH HHS R01 HL121527NIGMS NIH HHS P20 GM104357
6 · The paper itself

Abstract

Patients with chronic kidney disease (CKD) have a high cardiovascular mortality. CKD and heart failure (HF) coexist in up to 50% of patients, and both associate with inflammation. We aimed to define the cardiac phenotype of a novel swine model of CKD and test the hypothesis that inflammation of renal origin propels the development of precursors of HF in CKD. CKD was induced in 14 pigs, which were followed for 14 wk. Renal (multidetector computed tomography) and cardiac (echocardiography) hemodynamics were quantified before and 8 wk after single intrarenal administration of placebo or a biopolymer-fused peptide inhibitor of NF-κB that blocks NF-κB activity and decreases inflammatory activity (SynB1-ELP-p50i). Blood was collected to quantify cytokines (TNF-α, monocyte chemoattractant protein-1, and interleukins), markers of inflammation (C-reactive protein), and biomarkers of HF (atrial and brain natriuretic peptides). Pigs were then euthanized, and kidneys and hearts were studied ex vivo. Normal pigs were used as time-matched controls. Renal dysfunction in CKD was accompanied by cardiac hypertrophy and fibrosis, diastolic dysfunction, increased renal and cardiac expression of TNF-α, monocyte chemoattractant protein-1, and interleukins, canonical and noncanonical mediators of NF-κB signaling, circulating inflammatory factors, and biomarkers of HF. Notably, most of these changes were improved after intrarenal SynB1-SynB1-ELP-p50i, although cardiac inflammatory signaling remained unaltered. The translational traits of this model support its use as a platform to test novel technologies to protect the kidney and heart in CKD. A targeted inhibition of renal NF-κB signaling improves renal and cardiac function, suggesting an inflammatory renal-cardio axis underlying early HF pathophysiology in CKD.

Indexed as

AnimalsApoptosisBiomarkersCytokinesDiet, High-FatFemaleFibrosisHeart DiseasesKidneyMaleNF-kappa BRenal Insufficiency, ChronicSwineBiomarkersCytokinesNF-kappa Bchronic renal diseasecytokinesdiastolic dysfunctionelastin-like polypeptidenuclear factor-κΒ

Identifiers

PMID34396789
PMCPMC8560407
OpenAlexW3195004356

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.