Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis
Year: 2020
Type: article
Study design: Observational Study
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-F2t-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.
Authors: 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
Institutions: Columbia University Irving Medical Center, Columbia University, Mayo Clinic, Mayo Clinic in Florida, University of Nebraska Medical Center, New York State Psychiatric Institute, Texas Neurology, Duke University, California Pacific Medical Center, University of Kansas, University of Kentucky, University of California, San Francisco, University of California System, University of California, Irvine, The University of Texas Southwestern Medical Center, University of Iowa
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3015325769