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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume21
Issue number3-4
DOIs
StatePublished - Apr 2 2020

Keywords

  • Amyotrophic lateral sclerosis
  • biomarker
  • creatinine
  • oxidative stress
  • uric acid

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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