Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis,Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration ( IF 2.5 ) Pub Date : 2020-04-10 , DOI: 10.1080/21678421.2020.1746810
Hiroshi Mitsumoto ₁ , Diana C. Garofalo ₂ , Regina M. Santella ₃ , Eric J. Sorenson ₄ , Björn Oskarsson ₅ , J americo M. Fernandes ₆ , Howard Andrews ₇ , Jonathan Hupf ₁ , Madison Gilmore ₁ , Daragh Heitzman ₈ , Richard S. Bedlack ₉ , Jonathan S. Katz ₁₀ , Richard J. Barohn ₁₁ , Edward J. Kasarskis ₁₂ , Catherine lomen-Hoerth ₁₃ , Tahseen Mozaffar ₁₄ , Sharon P. Nations ₁₅ , Andrea J. Swenson ₁₆ , Pam Factor-Litvak ₂

Affiliation

Department of Neurology, Eleanor and Lou Gehrig ALS Center, Columbia University Irving Medical Center, New York, NY, USA,
Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA,
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA,
Department of Neurology, Mayo Clinic, Rochester, MN, USA,
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA,
Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA,
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,
Texas Neurology, PA, Dallas, TX, USA,
Department of Neurology, Duke University, Durham, NC, USA,
Forbes Norris ALS Center, California Pacific Medical Center, San Francisco, CA, USA,
Department of Neurology, University of Kansas, San Francisco, CA, USA,
Department of Neurology, University of Kentucky, San Francisco, CA, USA,
Department of Neurology, University of California, San Francisco, CA, USA,
Department of Neurology, University of California, Irvine, CA, USA,
Department of Neurology and Neurotherapeutics, University of Texas Southwestern, Dallas, TX, USA, and
Department of Neurology, University of Iowa, Iowa City, IA, USA

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.

中文翻译：

肌萎缩性侧索硬化症中的血浆肌酐和氧化应激生物标志物

目的：在大型流行病学队列研究（ALS COSMOS）中，确定基线时血浆肌酐（PCr），血浆尿酸（PUA）和尿液氧化应激（OS）生物标志物与ALSFRS-R之间的关联以及生存率表型患者群体（N = 355）。

方法：获得空腹血浆和首次尿样。在基线，随访中点附近和最终抽血时（死亡或死亡前）分析PCr，PUA，尿液中的8-氧-脱氧鸟苷（8-oxodG）和15-F _2t-异前列腺素（IsoP）。退出研究）。我们估计了基线和生存期这些生物标志物与ALSFRS-R之间的关联。

结果：在基线时，PCr与ALSFRS-R（Spearman r = 0.30），FVC百分比（％）（r = 0.20），PUA（r = 0.37）和8-oxodG（r = −0.13，所有p <0.05）相关）。基线PCr显着预测了存活率（调整的危险比0.28，p <0.001）。相对于最高的两个四分位数来说，最低的两个PCr四分位数的人从基线到死亡的时间最短。在所有三个时间点，PCr和ALSFRS-R值均显着相关（基线：r = 0.29，中点：r = 0.23，最终：r = 0.38，所有p <0.001）。PCr和PUA随时间显着下降，而OS生物标志物随时间显着增加。

结论：迄今为止，与PUA，8-oxodG和IsoP相比，PCr预测存活率最佳。尽管PCr代表肌肉质量的程度，但它也可能代表ALS中复杂的生化变化。由于该领域没有可靠的预后生物标志物，因此PCr的重要性值得通过ALS中的临床研究进行进一步研究。

更新日期：2020-04-10

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