Evidence map›Paper›PMID 25366137›Full record

ArticleCirculation. Cardiovascular genetics2014

Hypertensive renal injury is associated with gene variation affecting immune signaling.

Michael C Braun, Stacy M Herring, Nisha Gokul, Monique Monita, Rebecca Bell, Yaming Zhu, Manuel L Gonzalez-Garay, Scott E Wenderfer, Peter A Doris

Abstract read
In one paragraph

Article in Circulation. Cardiovascular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Journal of the American Heart Association · 2020
    Article
  6. Article
  7. Adaptive Immunity in Hypertension.Current hypertension reports · 2019
    Review
  8. Article
  9. Article
  10. Genetic Susceptibility to Hypertension-Induced Renal Injury.Hypertension (Dallas, Tex. : 1979) · 2018
    Article
  11. Renal inflammation and injury are associated with lymphangiogenesis in hypertension.American journal of physiology. Renal physiology · 2017
    Article
  12. Article
  13. Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.Journal of the American Society of Nephrology : JASN · 2016
    Article
  14. Article
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

9 authors.

Michael C BraunFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston.
Stacy M HerringFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston.
Nisha GokulFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston.
Monique MonitaFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston.
Rebecca BellFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston.
Yaming ZhuFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston.
Manuel L Gonzalez-GarayFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston.
Scott E WenderferFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston.
Peter A DorisFrom the Department of Pediatrics, Baylor College of Medicine (M.C.B., S.E.W.), and Institute of Molecular Medicine (S.M.H., N.G., M.M., R.B., Y.Z., M.L.G.-G., P.A.D.), University of Texas Health Science Center at Houston. peter.a.doris@uth.tmc.edu.

Funding

Hypertensive Renal InjuryR01DK081866 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI DORIS, PETER A · 2009 to 2017
$2.9M
HNF1 transcriptional control of renal oxidative stressR01DK069632 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI DORIS, PETER A · 2005 to 2009
$1.4M
Hypertensive Renal InjuryR56DK081866 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI DORIS, PETER A · 2012 to 2012
$100k
NIDDK NIH HHS R01 DK069632NIDDK NIH HHS R01DK069632NIDDK NIH HHS R01 DK081866NIDDK NIH HHS R01DK081866NIDDK NIH HHS R56 DK081866
6 · The paper itself

Abstract

backgroundThe spontaneously hypertensive rat (SHR) strain exists in lines that contrast strongly in susceptibility to renal injury in hypertension. These inbred lines share common ancestry, and only 13% of their genomes arise from different ancestors. METHODS AND

resultsWe used next gen sequencing to detect natural allelic variation in 5 genes of the immunoreceptor signaling pathway (IgH, Dok3, Src, Syk, and JunD) that arise from different ancestors in the injury-prone SHR-A3 and the resistant SHR-B2 lines. We created an intercross between these lines, and in the F2 progeny, we observed that the inheritance of haplotype blocks containing the SHR-A3 alleles of these 5 genes correlated with increased albuminuria and histological measures of renal injury. To test whether accumulated genetic variation in this pathway may create a therapeutic target in hypertensive renal injury, rats of both lines were treated with the immunosuppressant mycophenolate mofetil (MMF). MMF reduced proteinuria (albumin to creatinine ratio) from 6.6 to 1.2 mg/mg (P<0.001) in SHR-A3. Glomerular injury scores were reduced in MMF-treated SHR-A3 from 1.6 to 1.4 (P<0.002). Tubulo-interstitial injury was reduced in MMF-treated SHR-A3 from 2.62 to 2.0 (P=0.001). MMF treatment also reduced renal fibrosis in SHR-A3 (3.9 versus 2.0; P<0.001).

conclusionsPolygenic susceptibility to renal injury in hypertension arises in association with genetic variation in genes that participate in immune responses and is dramatically improved by reduction of immune system activity.

Indexed as

Genetic VariationSignal TransductionAlbuminuriaAllelesAnimalsBlood PressureGenetic Predisposition to DiseaseGlomerular Filtration RateHaplotypesHypertensionImmunosuppressive AgentsKidneyKidney DiseasesLymphocytesMycophenolic AcidRatsImmunosuppressive AgentsMycophenolic AcidReceptors, Immunologicgenomehypertensionkidneyrenal disease

Identifiers

PMID25366137
PMCPMC4270933

What Socratic holds

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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 Socratic graph.