Evidence map›Paper›PMID 34097714›Full record

ArticlePloS one2021

Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.

Nicholas A Maksimowski, James W Scholey, Vanessa R Williams, Nephrotic Syndrome Study Network (NEPTUNE)

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

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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

4 authors at 2 institutions in 1 country.

Nicholas A MaksimowskiInstitute of Medical Science, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-6925-9753
James W ScholeyInstitute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Vanessa R WilliamsInstitute of Medical Science, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0003-4626-8320
Nephrotic Syndrome Study Network (NEPTUNE)
University of Toronto · CAUniversity Health Network · CA

Funding

Training Program in Clinical & Translationa Research in Human Glomerular DiseaseU54DK083912 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KRETZLER, MATTHIAS · 2009 to 2023
$20.3M
NIDDK NIH HHS U54 DK083912
6 · The paper itself

Abstract

backgroundAngiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge.

methodsWe studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects.

resultsACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (CCL2 and TNF) correlated with ACE2 expression in males (TNF: r = -0.65, P < 0.0001; CCL2: r = -0.60, P < 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes.

conclusionsSex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.

Indexed as

AdolescentAdultAngiotensin-Converting Enzyme 2Chemokine CCL2ChildFemaleGlomerulosclerosis, Focal SegmentalHumansKidneyMaleMiddle AgedSex FactorsTransforming Growth Factor beta1Tumor Necrosis Factor-alphaACE2 protein, humanAngiotensin-Converting Enzyme 2CCL2 protein, humanChemokine CCL2TGFB1 protein, humanTransforming Growth Factor beta1Tumor Necrosis Factor-alpha

Identifiers

PMID34097714
PMCPMC8184004
OpenAlexW3172256625

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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.