Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis

Hiroshi Mitsumoto; Diana C Garofalo; Regina M Santella; Eric J Sorenson; Björn Oskarsson; J americo M Fernandes; Howard Andrews; Jonathan Hupf; Madison Gilmore; Daragh Heitzman; Richard S Bedlack; Jonathan S Katz; Richard J Barohn; Edward J Kasarskis; Catherine lomen-Hoerth; Tahseen Mozaffar; Sharon P Nations; Andrea J Swenson; Pam Factor-Litvak

doi:10.1080/21678421.2020.1746810

Journal article

Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis

Hiroshi Mitsumoto, Diana C Garofalo, Regina M Santella, Eric J Sorenson, Björn Oskarsson, J americo M Fernandes, Howard Andrews, Jonathan Hupf, Madison Gilmore, Daragh Heitzman, …

Amyotrophic lateral sclerosis and frontotemporal degeneration, Vol.21(3-4), pp.263-272

04/02/2020

DOI: 10.1080/21678421.2020.1746810

PMCID: PMC7373369

PMID: 32276554

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https://www.ncbi.nlm.nih.gov/pmc/articles/7373369View

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Abstract

Objective: To determine the associations between plasma creatinine (PCr), plasma uric acid (PUA), and urinary oxidative stress (OS) biomarkers with the ALSFRS-R at baseline and survival in a large epidemiological cohort study (ALS COSMOS) with a well-phenotyped patient population (N = 355). Methods: Fasting plasma and first void urine samples were obtained. PCr, PUA, urinary 8-oxo-deoxy guanosine (8-oxodG), and 15-F 2t -isoprostane (IsoP) were analyzed at baseline, near the midpoint of follow-up, and at the final blood draw (before death or withdrawal from study). We estimated associations between these biomarkers and the ALSFRS-R at baseline and survival. Results: At baseline, PCr correlated with ALSFRS-R (Spearman r = 0.30), percent (%) FVC (r = 0.20), PUA (r = 0.37), and 8-oxodG (r = −0.13, all p < 0.05). Baseline PCr significantly predicted survival (adjusted hazard ratio 0.28, p < 0.001). Time to death from baseline was shortest for those in the lowest two PCr quartiles relative to the highest two quartiles. PCr and ALSFRS-R values were significantly correlated at all three time points (baseline: r = 0.29, midpoint: r = 0.23, final: r = 0.38, all p < 0.001). PCr and PUA significantly declined over time, whereas OS biomarkers significantly increased over time. Conclusions: To date, PCr predicted survival the best, compared to PUA, 8-oxodG, and IsoP. Although PCr represents the degree of muscle mass, it may also represent complex biochemical changes in ALS. Because the field has no reliable prognostic biomarkers, the importance of PCr warrants further investigation through clinical studies in ALS.

Amyotrophic Lateral Sclerosis

Oxidative Stress

creatinine

biomarker

uric acid

Details

Title: Subtitle: Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis
Creators: Hiroshi Mitsumoto - Department of Neurology, Eleanor and Lou Gehrig ALS Center, Columbia University Irving Medical Center
Diana C Garofalo - Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center
Regina M Santella - Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center
Eric J Sorenson - Department of Neurology, Mayo Clinic
Björn Oskarsson - Department of Neurology, Mayo Clinic
J americo M Fernandes - Department of Neurological Sciences, University of Nebraska Medical Center
Howard Andrews - Data Coordinating Center (DCC), Mailman School of Public Health Biostatistics Department, Columbia University Irving Medical Center, New York State Psychiatric Institute & Department of Psychiatry, Columbia University
Jonathan Hupf - Department of Neurology, Eleanor and Lou Gehrig ALS Center, Columbia University Irving Medical Center
Madison Gilmore - Department of Neurology, Eleanor and Lou Gehrig ALS Center, Columbia University Irving Medical Center
Daragh Heitzman - Texas Neurology
Richard S Bedlack - Department of Neurology, Duke University
Jonathan S Katz - Forbes Norris ALS Center, California Pacific Medical Center
Richard J Barohn - Department of Neurology, University of Kansas
Edward J Kasarskis - Department of Neurology, University of Kentucky
Catherine lomen-Hoerth - Department of Neurology, University of California
Tahseen Mozaffar - Department of Neurology, University of California
Sharon P Nations - Department of Neurology and Neurotherapeutics, University of Texas Southwestern
Andrea J Swenson - Department of Neurology, University of Iowa
Pam Factor-Litvak - Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center
Resource Type: Journal article
Publication Details: Amyotrophic lateral sclerosis and frontotemporal degeneration, Vol.21(3-4), pp.263-272
DOI: 10.1080/21678421.2020.1746810
PMID: 32276554
PMCID: PMC7373369
NLM abbreviation: Amyotroph Lateral Scler Frontotemporal Degener
ISSN: 2167-8421
eISSN: 2167-9223
Publisher: Taylor & Francis
Grant note: William Spina Foundation ALS Ride for Life Judith and Jean Pape Adams Charitable Foundation R01-ES016348 / NIEHS Anthony Senerchia Family Foundation MDA Wings Over Wall Street
Language: English
Date published: 04/02/2020
Academic Unit: Neurology
Record Identifier: 9984066338702771

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