Elevated lipoxygenase and cytochrome P450 products predict progression of chronic kidney disease.

Case-Control Studies Cohort Studies Cytochrome P-450 Enzyme System / metabolism Disease Progression Female Humans Hydroxyeicosatetraenoic Acids / metabolism Kidney Failure, Chronic / diagnosis Lipoxygenase / metabolism Male Middle Aged Renal Insufficiency, Chronic / complications
CKD cardiovascular heart failure progression prostaglandins

Journal

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402

Informations de publication

Date de publication:
01 02 2020
Historique:
received: 28 03 2018
accepted: 14 06 2018
pubmed: 24 8 2018
medline: 12 9 2020
entrez: 24 8 2018
Statut: ppublish

Résumé

The clinical relevance of arachidonic acid (AA) metabolites in chronic kidney disease (CKD) progression is poorly understood. We aimed to compare the concentrations of 85 enzymatic pathway products of AA metabolism in patients with CKD who progressed to end-stage kidney disease (ESKD) versus patients who did not in a subcohort of Chronic Renal Insufficiency Cohort (CRIC) and to estimate the risk of CKD progression and major cardiovascular events by levels of AA metabolites and their link to enzymatic metabolic pathways. A total 123 patients in the CRIC study who progressed to ESKD were frequency matched with 177 nonprogressors and serum eicosanoids were quantified by mass spectrometry. We applied serum collected at patients' Year 1 visit and outcome of progression to ESKD was ascertained over the next 10 years. We used logistic regression models for risk estimation. Baseline 15-hydroxyeicosatetraenoate (HETE) and 20-HETE levels were significantly elevated in progressors (false discovery rate Q ≤ 0.026). The median 20-HETE level was 7.6 pmol/mL [interquartile range (IQR) 4.2-14.5] in progressors and 5.4 pmol/mL (IQR 2.8-9.4) in nonprogressors (P < 0.001). In an adjusted model, only 20-HETE independently predicted CKD progression. Each 1 standard deviation increase in 20-HETE was independently associated with 1.45-fold higher odds of progression (95% confidence interval 1.07-1.95; P = 0.017). Principal components of lipoxygenase (LOX) and cytochrome P450 (CYP450) pathways were independently associated with CKD progression. We found higher odds of CKD progression associated with higher 20-HETE, LOX and CYP450 metabolic pathways. These alterations precede CKD progression and may serve as targets for interventions aimed at halting progression.

Sections du résumé

BACKGROUND
The clinical relevance of arachidonic acid (AA) metabolites in chronic kidney disease (CKD) progression is poorly understood. We aimed to compare the concentrations of 85 enzymatic pathway products of AA metabolism in patients with CKD who progressed to end-stage kidney disease (ESKD) versus patients who did not in a subcohort of Chronic Renal Insufficiency Cohort (CRIC) and to estimate the risk of CKD progression and major cardiovascular events by levels of AA metabolites and their link to enzymatic metabolic pathways.
METHODS
A total 123 patients in the CRIC study who progressed to ESKD were frequency matched with 177 nonprogressors and serum eicosanoids were quantified by mass spectrometry. We applied serum collected at patients' Year 1 visit and outcome of progression to ESKD was ascertained over the next 10 years. We used logistic regression models for risk estimation.
RESULTS
Baseline 15-hydroxyeicosatetraenoate (HETE) and 20-HETE levels were significantly elevated in progressors (false discovery rate Q ≤ 0.026). The median 20-HETE level was 7.6 pmol/mL [interquartile range (IQR) 4.2-14.5] in progressors and 5.4 pmol/mL (IQR 2.8-9.4) in nonprogressors (P < 0.001). In an adjusted model, only 20-HETE independently predicted CKD progression. Each 1 standard deviation increase in 20-HETE was independently associated with 1.45-fold higher odds of progression (95% confidence interval 1.07-1.95; P = 0.017). Principal components of lipoxygenase (LOX) and cytochrome P450 (CYP450) pathways were independently associated with CKD progression.
CONCLUSIONS
We found higher odds of CKD progression associated with higher 20-HETE, LOX and CYP450 metabolic pathways. These alterations precede CKD progression and may serve as targets for interventions aimed at halting progression.

Identifiants

DOI: 10.1093/ndt/gfy232 PMID: 30137494 PMC: PMC7391277
pubmed: 30137494
pii: 5059540
doi: 10.1093/ndt/gfy232
pmc: PMC7391277
doi:

Substances chimiques

Hydroxyeicosatetraenoic Acids 0
20-hydroxy-5,8,11,14-eicosatetraenoic acid 79551-86-3
Cytochrome P-450 Enzyme System 9035-51-2
Lipoxygenase EC 1.13.11.12

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

303-312

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK072231
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060963
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK089503
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061022
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000003
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000439
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060990
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK106523
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR029879
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061028
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000433
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060984
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061021
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK060990
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060980
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024131
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK082841
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104940
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR013987
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000424
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR016500
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109036
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060902
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002003
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK081943
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK097153
Pays : United States

Investigateurs

Lawrence J Appel (LJ)
Alan S Go (AS)
Jiang He (J)
John W Kusek (JW)
James P Lash (JP)
Panduranga S Rao (PS)
Mahboob Rahman (M)
Raymond R Townsend (RR)

Informations de copyright

© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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Auteurs

Farsad Afshinnia (F)

Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI, USA.

Lixia Zeng (L)

Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI, USA.

Jaeman Byun (J)

Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI, USA.

Stefanie Wernisch (S)

Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI, USA.

Rajat Deo (R)

Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jing Chen (J)

Division of Nephrology and Hypertension, Tulane University, New Orleans, LA, USA.

Lee Hamm (L)

Division of Nephrology and Hypertension, Tulane University, New Orleans, LA, USA.

Edgar R Miller (ER)

Department of Internal Medicine, Jones Hopkins University, Baltimore, MD, USA.

Eugene P Rhee (EP)

Department of Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.

Michael J Fischer (MJ)

Department of Medicine, University of Illinois, Center of Innovation for Complex Chronic Healthcare, Jesse Brown VAMC, Chicago, IL, USA.

Kumar Sharma (K)

Department of Internal Medicine-Nephrology, University of Texas Health San Antonio, San Antonio, TX, USA.

Harold I Feldman (HI)

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.

George Michailidis (G)

Department of Statistics, University of Florida, Gainesville, FL, USA.

Subramaniam Pennathur (S)

Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI, USA.
Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI, USA.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

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questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Elevated lipoxygenase and cytochrome P450...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Elevated lipoxygenase and cytochrome P450...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Hémoprotéines › Cytochromes › Cytochrome P-450 enzyme system › Elevated lipoxygenase and cytochrome P450...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Elevated lipoxygenase and cytochrome P450...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Elevated lipoxygenase and cytochrome P450...
questionsmedicales.fr › Lipides › Acides gras › Acides gras insaturés › Acides gras indispensables › Acides arachidoniques › Acide hydroxyeïcosatétraénoïque › Elevated lipoxygenase and cytochrome P450...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Métalloprotéines › Protéines de liaison au fer › Protéines à fer non hème › Lipoxygénases › Lipoxygenase › Elevated lipoxygenase and cytochrome P450...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Elevated lipoxygenase and cytochrome P450...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Insuffisance rénale chronique › Elevated lipoxygenase and cytochrome P450...