Evidence map›Paper›PMID 34485290›Full record

ArticleFrontiers in cell and developmental biology2021

Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease.

Benjamin P Larkin, Long T Nguyen, Miao Hou, Sarah J Glastras, Hui Chen, Rosy Wang, Carol A Pollock, Sonia Saad

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

Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

7 citing papers in PubMed, 9 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

8 authors at 4 institutions in 2 countries.

Benjamin P LarkinRenal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Long T NguyenRenal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Miao HouDepartment of Cardiology, Children's Hospital of Soochow University, Suzhou, China.
Sarah J GlastrasRenal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Hui ChenFaculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia.
Rosy WangRenal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Carol A PollockRenal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Sonia SaadRenal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Royal North Shore Hospital · AUUniversity of Sydney · AUSoochow University · CNUniversity of Technology Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMaternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring.

methodsFemale C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint.

resultsOffspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress.

conclusionGestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.

Indexed as

chronic kidney diseaseDNA methylationfetal programmingmaternal obesityobesity

Identifiers

PMID34485290
PMCPMC8416283
OpenAlexW3195663101

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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.