Kidney tubule health, mineral metabolism and adverse events in persons with CKD in SPRINT.

Acute Kidney Injury Aged Aged, 80 and over Albuminuria / complications Biomarkers Blood Pressure / physiology Glomerular Filtration Rate / physiology Humans Hypertension Kidney Tubules Lipocalin-2 Middle Aged Minerals Renal Insufficiency, Chronic / complications Uromodulin
adverse events biomarkers chronic kidney disease hypertension kidney tubule

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:
22 08 2022
Historique:
received: 19 05 2021
pubmed: 3 9 2021
medline: 25 8 2022
entrez: 2 9 2021
Statut: ppublish

Résumé

Measures of kidney tubule health are risk markers for acute kidney injury (AKI) in persons with chronic kidney disease (CKD) during hypertension treatment, but their associations with other adverse events (AEs) are unknown. Among 2377 Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD, we measured at baseline eight urine biomarkers of kidney tubule health and two serum biomarkers of mineral metabolism pathways that act on the kidney tubules. Cox proportional hazards models were used to evaluate biomarker associations with risk of a composite of pre-specified serious AEs (hypotension, syncope, electrolyte abnormalities, AKI, bradycardia and injurious falls) and outpatient AEs (hyperkalemia and hypokalemia). At baseline, the mean age was 73 ± 9 years and mean estimated glomerular filtration rate (eGFR) was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.8 years, 716 (30%) participants experienced the composite AE. Higher urine interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1), lower urine uromodulin (UMOD) and higher serum fibroblast growth factor-23 were individually associated with higher risk of the composite AE outcome in multivariable-adjusted models including eGFR and albuminuria. When modeling biomarkers in combination, higher NGAL [hazard ratio (HR) = 1.08 per 2-fold higher biomarker level, 95% confidence interval (CI) 1.03-1.13], higher MCP-1 (HR = 1.11, 95% CI 1.03-1.19) and lower UMOD (HR = 0.91, 95% CI 0.85-0.97) were each associated with higher composite AE risk. Biomarker associations did not vary by intervention arm (P > 0.10 for all interactions). Among persons with CKD, several kidney tubule biomarkers are associated with higher risk of AEs during hypertension treatment, independent of eGFR and albuminuria.

Sections du résumé

BACKGROUND
Measures of kidney tubule health are risk markers for acute kidney injury (AKI) in persons with chronic kidney disease (CKD) during hypertension treatment, but their associations with other adverse events (AEs) are unknown.
METHODS
Among 2377 Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD, we measured at baseline eight urine biomarkers of kidney tubule health and two serum biomarkers of mineral metabolism pathways that act on the kidney tubules. Cox proportional hazards models were used to evaluate biomarker associations with risk of a composite of pre-specified serious AEs (hypotension, syncope, electrolyte abnormalities, AKI, bradycardia and injurious falls) and outpatient AEs (hyperkalemia and hypokalemia).
RESULTS
At baseline, the mean age was 73 ± 9 years and mean estimated glomerular filtration rate (eGFR) was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.8 years, 716 (30%) participants experienced the composite AE. Higher urine interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1), lower urine uromodulin (UMOD) and higher serum fibroblast growth factor-23 were individually associated with higher risk of the composite AE outcome in multivariable-adjusted models including eGFR and albuminuria. When modeling biomarkers in combination, higher NGAL [hazard ratio (HR) = 1.08 per 2-fold higher biomarker level, 95% confidence interval (CI) 1.03-1.13], higher MCP-1 (HR = 1.11, 95% CI 1.03-1.19) and lower UMOD (HR = 0.91, 95% CI 0.85-0.97) were each associated with higher composite AE risk. Biomarker associations did not vary by intervention arm (P > 0.10 for all interactions).
CONCLUSIONS
Among persons with CKD, several kidney tubule biomarkers are associated with higher risk of AEs during hypertension treatment, independent of eGFR and albuminuria.

Identifiants

DOI: 10.1093/ndt/gfab255 PMID: 34473302 PMC: PMC9649818
pubmed: 34473302
pii: 6362902
doi: 10.1093/ndt/gfab255
pmc: PMC9649818
doi:

Substances chimiques

Biomarkers 0
Lipocalin-2 0
Minerals 0
Uromodulin 0

Types de publication

Clinical Trial Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1637-1646

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR000433
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK098234
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000064
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000075
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000003
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000050
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001420
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025755
Pays : United States
Organisme : NIDDK NIH HHS
ID : K24 DK110427
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900048C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000005
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900040C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900046C
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103337
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001064
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025752
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025771
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144112
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000093
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900049C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900047C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000439
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000073
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000002
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000105
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024134
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003142
Pays : United States

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of ERA. All rights reserved.

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Auteurs

Simon B Ascher (SB)

Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA.
Division of Hospital Medicine, University of California Davis, Sacramento, CA, USA.

Rebecca Scherzer (R)

Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA.

Michelle M Estrella (MM)

Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA.

Jarett D Berry (JD)

Divison of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

James A de Lemos (JA)

Divison of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Vasantha K Jotwani (VK)

Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA.

Pranav S Garimella (PS)

Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA, USA.

Rakesh Malhotra (R)

Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA, USA.

Alexander L Bullen (AL)

Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA, USA.
Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

Ronit Katz (R)

Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.

Walter T Ambrosius (WT)

Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Alfred K Cheung (AK)

Division of Nephrology and Hypertension, University of Utah Health, Salt Lake City, UT, USA.
Department of Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT, USA.

Michel Chonchol (M)

Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, USA.

Anthony A Killeen (AA)

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
ORCID: 0000-0003-1629-9468

Joachim H Ix (JH)

Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA, USA.
Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

Michael G Shlipak (MG)

Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA.

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Classifications MeSH

questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Maladies du rein › Insuffisance rénale › Atteinte rénale aigüe › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations urologiques › Protéinurie › Albuminurie › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Hémodynamique › Pression sanguine › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques des voies urinaires › Débit de filtration glomérulaire › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Hypertension artérielle › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Néphrons › Tubules rénaux › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Lipocaline-2 › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Produits chimiques inorganiques › Minéraux › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Insuffisance rénale chronique › Kidney tubule health, mineral metabolism and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Protéines liées au GPI › Uromoduline › Kidney tubule health, mineral metabolism and...