Evidence map›Paper›PMID 25261195›Full record

ArticleCritical care (London, England)2014

Endothelial dysfunction and renal fibrosis in endotoxemia-induced oliguric kidney injury: possible role of LPS-binding protein.

Giuseppe Castellano, Alessandra Stasi, Angelica Intini, Margherita Gigante, Anna Maria Di Palma, Chiara Divella, Giuseppe Stefano Netti, Clelia Prattichizzo, Paola Pontrelli, Antonio Crovace and 6 more

Open access · goldAbstract read
In one paragraph

Article in Critical care (London, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

24 citing papers in PubMed, 58 citations in OpenAlex.

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  11. Porcine models of acute kidney injury.American journal of physiology. Renal physiology · 2021
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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

16 authors at 3 institutions in 1 country.

Giuseppe Castellano
Alessandra Stasi
Angelica Intini
Margherita Gigante
Anna Maria Di Palma
Chiara Divella
Giuseppe Stefano Netti
Clelia Prattichizzo
Paola Pontrelli
Antonio Crovace
Francesco Staffieri
Enrico Fiaccadori
Nicola Brienza
Giuseppe Grandaliano
Giovanni Pertosa
Loreto Gesualdo
University of Bari Aldo Moro · ITUniversity of Foggia · ITUniversity of Parma · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe pathophysiology of endotoxemia-induced acute kidney injury (AKI) is characterized by an intense activation of the host immune system and renal resident cells by lipopolysaccharide (LPS) and derived proinflammatory products. However, the occurrence of renal fibrosis in this setting has been poorly investigated. The aim of the present study was to investigate the possible association between endothelial dysfunction and acute development of tissue fibrosis in a swine model of LPS-induced AKI. Moreover, we studied the possible effects of coupled plasma filtration adsorption (CPFA) in this setting.

methodsAfter 9 hours from LPS infusion and 6 hours of CPFA treatment, histologic and biochemical changes were analyzed in pigs. Apoptosis and endothelial dysfunction were assessed on renal biopsies. The levels of LPS-binding protein (LBP) were quantified with enzyme-linked immunosorbent assay (ELISA). Endothelial cells (ECs) were stimulated in vitro with LPS and cultured in the presence of swine sera and were analyzed with FACS and real-time RT-PCR.

resultsIn a swine model of LPS-induced AKI, we observed that acute tubulointerstitial fibrosis occurred within 9 hours from LPS injection. Acute fibrosis was associated with dysfunctional alpha-smooth muscle actin (α-SMA)+ ECs characterized by active proliferation (Ki-67+) without apoptosis (caspase-3-). LPS led to EC dysfunction in vitro with significant vimentin and N-cadherin expression and increased collagen I mRNA synthesis. Therapeutic intervention by citrate-based CPFA significantly prevented acute fibrosis in endotoxemic animals, by preserving the EC phenotype in both peritubular capillaries and renal arteries. We found that the removal of LBP from plasma was crucial to eliminate the effects of LPS on EC dysfunction, by blocking LPS-induced collagen I production.

conclusionsOur data indicate that EC dysfunction might be pivotal in the acute development of tubulointerstitial fibrosis in LPS-induced AKI. Selective removal of the LPS adaptor protein LBP might represent a future therapeutic option to prevent EC dysfunction and tissue fibrosis in endotoxemia-induced AKI.

Indexed as

Acute Kidney InjuryAcute-Phase ProteinsAnimalsCarrier ProteinsCaspase 3Disease Models, AnimalEndothelial CellsEnzyme-Linked Immunosorbent AssayFemaleFibrosisKidneyLipopolysaccharide-Binding ProteinMembrane GlycoproteinsSwineAcute-Phase ProteinsCarrier ProteinsCaspase 3Lipopolysaccharide-Binding ProteinMembrane Glycoproteins

Identifiers

PMID25261195
PMCPMC4205288
OpenAlexW2046159430

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.