Evidence map›Paper›PMID 29980651›Full record

ArticleJournal of the American Society of Nephrology : JASN2018

Mechanisms Underlying Increased TIMP2 and IGFBP7 Urinary Excretion in Experimental AKI.

Ali C M Johnson, Richard A Zager

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

Article in Journal of the American Society of Nephrology : JASN, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 3 pooled it
8.4field-weighted citation impact, top 1% 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

65 citing papers in PubMed, 3 syntheses or guidelines pooled it, 132 citations in OpenAlex.

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  20. Current updates in radiocontrast-associated acute kidney injury.Proceedings (Baylor University. Medical Center) · 2024
    Review

5 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 1 country.

Ali C M JohnsonClinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; and.
Richard A ZagerClinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; and dzager@fredhutch.org.ORCID 0000-0002-4530-5612
Fred Hutch Cancer Center · USUniversity of Washington · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecent clinical data support the utility/superiority of a new AKI biomarker ("NephroCheck"), the arithmetic product of urinary TIMP × IGFBP7 concentrations. However, the pathophysiologic basis for its utility remains ill defined.

methodsTo clarify this issue, CD-1 mice were subjected to either nephrotoxic (glycerol, maleate) or ischemic AKI. Urinary TIMP2/IGFBP7 concentrations were determined at 4 and 18 hours postinjury and compared with urinary albumin levels. Gene transcription was assessed by measuring renal cortical and/or medullary TIMP2/IGFBP7 mRNAs (4 and 18 hours after AKI induction). For comparison, the mRNAs of three renal "stress" biomarkers (NGAL, heme oxygenase 1, and p21) were assessed. Renal cortical TIMP2/IGFBP7 protein was gauged by ELISA. Proximal tubule-specific TIMP2/IGFBP7 was assessed by immunohistochemistry.

resultsEach AKI model induced prompt (4 hours) and marked urinary TIMP2/IGFBP7 increases without an increase in renal cortical concentrations. Furthermore, TIMP2/IGFBP7 mRNAs remained at normal levels. Endotoxemia also failed to increase TIMP2/IGFBP7 mRNAs. In contrast, each AKI model provoked massive NGAL, HO-1, and p21 mRNA increases, confirming that a renal "stress response" had occurred. Urinary albumin rose up to 100-fold and strongly correlated (

conclusionsAKI-induced urinary TIMP2/IGFBP7 elevations are not due to stress-induced gene transcription. Rather, increased filtration, decreased tubule reabsorption, and proximal tubule cell TIMP2/IGFBP7 urinary leakage seem to be the most likely mechanisms.

Indexed as

Acute Kidney InjuryAnimalsBiomarkersBiopsy, NeedleDisease Models, AnimalEnzyme-Linked Immunosorbent AssayImmunohistochemistryInsulin-Like Growth Factor Binding ProteinsKidney Tubules, ProximalMaleMiceMice, Inbred StrainsRandom AllocationSensitivity and SpecificityTissue Inhibitor of Metalloproteinase-2Biomarkersinsulin-like growth factor binding protein-related protein 1Insulin-Like Growth Factor Binding ProteinsTissue Inhibitor of Metalloproteinase-2acute renal failurebiomarkersglycerol-induced rhabdomyolysisischemia-reperfusionmaleate nephrotoxicity

Identifiers

PMID29980651
PMCPMC6065093
OpenAlexW2838731432

What OpenQuestion holds

Textmetadata
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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.