Evidence map›Paper›PMID 31055735›Full record

ArticleTranslational stroke research2020

Chronic Kidney Disease Increases Cerebral Microbleeds in Mouse and Man.

Wei Ling Lau, Ane C F Nunes, Vitaly Vasilevko, David Floriolli, Long Lertpanit, Javad Savoj, Maria Bangash, Zhihui Yao, Krunal Shah, Sameen Naqvi and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational stroke research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.7field-weighted citation impact, top 3% 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

55 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Sex-specific cardiac dysfunction in mice with chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Cognitive impairment in chronic kidney disease: role of brain imaging, functional imaging, electroencephalography, cerebrospinal fluid biomarkers and sensors.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

14 authors at 1 institution in 2 countries.

Wei Ling LauDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA. wllau@uci.edu.ORCID 0000-0002-3118-1073
Ane C F NunesDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
Vitaly VasilevkoInstitute for Memory Impairments and Neurological Disorders, University of California, 1111 GNRF, Irvine, 92697-4540, CA, USA.
David FloriolliDepartment of Radiological Sciences, Neuroradiology, University of California, Irvine, CA, USA.
Long LertpanitDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
Javad SavojDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
Maria BangashDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
Zhihui YaoDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
Krunal ShahDepartment of Neurology, University of California, Irvine, CA, USA.
Sameen NaqviDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
Annlia Paganini-HillDepartment of Neurology, University of California, Irvine, CA, USA.
Nosratola D VaziriDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
David H CribbsInstitute for Memory Impairments and Neurological Disorders, University of California, 1111 GNRF, Irvine, 92697-4540, CA, USA.
Mark FisherDepartment of Neurology, University of California, Irvine, CA, USA.
University of California, Irvine · US

Funding

HEMORHOLOGICAL FACTORS IN CEREBRAL ISCHEMIAR01NS020989 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRIBBS, DAVID HASTINGS, FISHER, MARK J · 1985 to 2022
$9.1M
NINDS NIH HHS NS20989NINDS NIH HHS R01 NS020989
6 · The paper itself

Abstract

Brain microbleeds are increased in chronic kidney disease (CKD) and their presence increases risk of cognitive decline and stroke. We examined the interaction between CKD and brain microhemorrhages (the neuropathological substrate of microbleeds) in mouse and cell culture models and studied progression of microbleed burden on serial brain imaging from humans. Mouse studies: Two CKD models were investigated: adenine-induced tubulointerstitial nephritis and surgical 5/6 nephrectomy. Cell culture studies: bEnd.3 mouse brain endothelial cells were grown to confluence, and monolayer integrity was measured after exposure to 5-15% human uremic serum or increasing concentrations of urea. Human studies: Progression of brain microbleeds was evaluated on serial MRI from control, pre-dialysis CKD, and dialysis patients. Microhemorrhages were increased 2-2.5-fold in mice with CKD independent of higher blood pressure in the 5/6 nephrectomy model. IgG staining was increased in CKD animals, consistent with increased blood-brain barrier permeability. Incubation of bEnd.3 cells with uremic serum or elevated urea produced a dose-dependent drop in trans-endothelial electrical resistance. Elevated urea induced actin cytoskeleton derangements and decreased claudin-5 expression. In human subjects, prevalence of microbleeds was 50% in both CKD cohorts compared with 10% in age-matched controls. More patients in the dialysis cohort had increased microbleeds on follow-up MRI after 1.5 years. CKD disrupts the blood-brain barrier and increases brain microhemorrhages in mice and microbleeds in humans. Elevated urea alters the actin cytoskeleton and tight junction proteins in cultured endothelial cells, suggesting that these mechanisms explain (at least in part) the microhemorrhages and microbleeds observed in the animal and human studies.

Indexed as

Actin CytoskeletonAnimalsCells, CulturedCerebral HemorrhageDisease Models, AnimalEndothelial CellsFemaleHumansMaleMice, Inbred C57BLMiddle AgedRenal Insufficiency, ChronicTight JunctionsBrain MRIChronic kidney diseaseEndothelial cell cultureMicrobleedsMouse model

Identifiers

PMID31055735
PMCPMC6957561
OpenAlexW2944741800

What OpenQuestion holds

Textmetadata
LicenceTDM
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.