Evidence map›Paper›PMID 10980139›Full record

ArticleThe American journal of pathology2000

Changes in free and esterified cholesterol: hallmarks of acute renal tubular injury and acquired cytoresistance.

R A Zager, T F Kalhorn

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Cellular and Molecular Mechanisms of AKI.Journal of the American Society of Nephrology : JASN · 2016
    Review
  5. Article
  6. Article
  7. 'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2013
    Review
  8. Article
  9. HMG-CoA reductase activation and urinary pellet cholesterol elevations in acute kidney injury.Clinical journal of the American Society of Nephrology : CJASN · 2011
    Article
  10. Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning.American journal of physiology. Regulatory, integrative and comparative physiology · 2010
    Article
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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

2 authors at 1 institution in 2 countries.

R A ZagerFred Hutchinson Cancer Research Center and the University of Washington, Seattle, Washington 98109-1024, USA. dzager@fhcrc.org
T F Kalhorn
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

SEPSIS INDUCED ACUTE RENAL FAILURER01DK038432 · NIDDK · UNIVERSITY OF WASHINGTON · PI ZAGER, RICHARD A. · 1988 to 2015
$2.1M
ACUTE RENAL FAILURE--IMPACT OF FLUORINATED ANESTHETICSR01DK054200 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ZAGER, RICHARD A. · 1998 to 2001
$520k
NIDDK NIH HHS R01 DK038432NIDDK NIH HHS R01 DK 38432NIDDK NIH HHS R01 DK 54200
6 · The paper itself

Abstract

Acute tubular cell injury is accompanied by plasma membrane phospholipid breakdown. Although cholesterol is a dominant membrane lipid which interdigitates with, and impacts, phospholipid homeostasis, its fate during the induction and recovery phases of acute renal failure (ARF) has remained ill defined. The present study was performed to ascertain whether altered cholesterol expression is a hallmark of evolving tubular damage. Using gas chromatographic analysis, free cholesterol (FC) and esterified cholesterol (CE) were quantified in: 1) isolated mouse proximal tubule segments (PTS) after 30 minutes of hypoxic or oxidant (ferrous ammonium sulfate) injury; 2) cultured proximal tubule (HK-2) cells after 4 or 18 hours of either ATP depletion/Ca(2+) ionophore- or ferrous ammonium sulfate-mediated injury; and 3) in renal cortex 18 hours after induction of glycerol-induced myoglobinuric ARF, a time corresponding to the so-called "acquired cytoresistance" state (ie, resistance to further renal damage). Hypoxic and oxidant injury each induced approximately 33% decrements in CE (but not FC) levels in PTS, corresponding with lethal cell injury ( approximately 50 to 60% LDH release). When comparable CE declines were induced in normal PTS by exogenous cholesterol esterase treatment, proportionate lethal cell injury resulted. During models of slowly evolving HK-2 cell injury, progressive CE increments occurred: these were first noted at 4 hours, and reached approximately 600% by 18 hours. In vivo myoglobinuric ARF produced comparable renal cortical CE (and to a lesser extent FC) increments. Renal CE accumulation strikingly correlated with the severity of ARF (eg, blood urea nitrogen versus CE; r, 0.84). Mevastatin blocked cholesterol accumulation in injured HK-2 cells, indicating de novo synthesis was responsible. Acute tubule injury first lowers, then raises, tubule cholesterol content. Based on previous observations that cholesterol has cytoprotectant properties, the present findings have potential relevance for both the induction and maintenance phases of ARF.

Indexed as

CytoprotectionAcute Kidney InjuryAnimalsCell HypoxiaCell SurvivalCholesterolCholesterol EstersCholesterol OxidaseChromatography, GasFerrous CompoundsGlycerolKidney Tubules, ProximalL-Lactate DehydrogenaseLovastatinMaleMiceammonium ferrous sulfateCholesterolCholesterol EstersCholesterol OxidaseFerrous CompoundsGlycerolL-Lactate DehydrogenaseLovastatinmevastatinQuaternary Ammonium CompoundsSterol Esterase

Identifiers

PMID10980139
PMCPMC1885711
OpenAlexW1973352737

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.