Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis

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

doi:10.1080/21678421.2020.1746810

Cited by 27 publications

(26 citation statements)

References 47 publications

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“…In the present study, we also observed that the serum creatinine was positively correlated with the ALSFRS‐R score, and inversely linked to disease progression rate (Δ ALSFRS‐R), which was similar to the result from a meta‐analysis 12 . Besides, Mitsumoto et al also found that the plasma creatinine predicted ALS survival the best, compared to the oxidative stress biomarkers, including plasma uric acid, urinary 8‐oxo‐deoxy guanosine (8‐oxodG), and 15‐F2t‐isoprostane (IsoP) 16 . The application of creatinine as an outcome in clinical trial could significantly reduce the sample size by 21.5% 10 .…”

Section: Discussionsupporting

confidence: 64%

Decreased serum creatinine levels predict short survival in amyotrophic lateral sclerosis

Guo

et al. 2021

Ann Clin Transl Neurol

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Objective To explore the associations between serum creatinine and creatine kinase (CK) levels with survival in male and female ALS patients. Methods A prospective cohort study was carried out including 346 ALS patients with repeated serum creatinine and CK measurements. Kaplan Meier analysis and multivariable Cox regression were used to perform survival analysis. Results There were 218 male and 128 female patients, and the males had significantly higher baseline serum creatinine and CK levels than females. After multivariable Cox regression analysis, lower baseline serum creatinine levels were associated with a short survival in both male (≤61 μmol/L, HR: 1.629; 95%CI: 1.168–2.273) and female ALS patients (≤52 μmol/L, HR: 1.677; 95%CI: 1.042–2.699), whereas, the serum CK levels were not correlated with survival. Besides, creatinine levels were positively associated with ALSFRS‐R scores, and inversely with the decline rate of ALSFRS‐R per month. During follow‐up, serum creatinine levels tended to be decreased along with the disease progression, and the higher decline rate of creatinine per month (>1.5) showed significantly shorter survival, compared to the lower group (≤1.5) (30.0 months vs. 65.0 months, Chi square = 28.25, P < 0.0001). Interpretation Serum creatinine could be a reliable and easily accessible prognostic chemical marker for ALS, and decreased baseline creatinine levels could predict a poor prognosis and a short survival in both male and female ALS patients.

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Section: Discussionsupporting

confidence: 64%

Decreased serum creatinine levels predict short survival in amyotrophic lateral sclerosis

Guo

et al. 2021

Ann Clin Transl Neurol

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“…ALSFRS-R and serum creatinine levels were signi cantly lower in the severe group than in the mild group. These results were consistent with those of a previous study suggesting that plasma creatinine level correlates with ALS functional rating scale-revised (ALSFRS-R) and percent forced vital capacity (FVC) and signi cantly predicted survival [23].…”

Section: Discussionsupporting

confidence: 92%

Increased Cerebrospinal Fluid Adenosine 5'-triphosphate in Patients with Amyotrophic Lateral Sclerosis

Nukui

Matsui

Niimi

et al. 2020

Preprint

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Background: Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined CSF ATP levels in patients with ALS whether it can be a useful biomarker in ALS. Methods: Forty-eight CSF samples from 45 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated. Results: ALSFRS-R (37.9 ± 5.7 vs. 42.4 ± 2.8, p<0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis (r = -0.3862, p < 0.01). Conclusions: Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.

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“…Many of these factors have been previously associated with the rate of ALSFRS decline including weight, FVC and age (Mandrioli et al [2015]). Plasma creatinine has been previously associated with outcome in ALS and may act as a marker of muscle reserve (Mitsumoto et al [2020]). The observation of different relative effect sizes between groups for cholesterol and weight suggests that cholesterol is not acting only as a proxy for weight.…”

Section: Resultsmentioning

confidence: 99%

Penalized longitudinal mixed models with latent group structure, with an application in neurodegenerative diseases

Hatami

Perrakis

Cooper‐Knock

et al. 2020

Preprint

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SummaryLarge-scale longitudinal data are often heterogeneous, spanning latent subgroups such as disease subtypes. In this paper, we present an approach called longitudinal joint cluster regression (LJCR) for penalized mixed modelling in the latent group setting. LJCR captures latent group structure via a mixture model that includes both the multivariate distribution of the covariates and a regression model for the response. The longitudinal dynamics of each individual are modeled using a random effect intercept and slope model. Inference is done via a profile likelihood approach that can handle high-dimensional covariates via ridge penalization. LJCR is motivated by questions in neurodegenerative disease research, where latent subgroups may reflect heterogeneity with respect to disease presentation, progression and diverse subject-specific factors. We study the performance of LJCR in the context of two longitudinal datasets: a simulation study and a study of amyotrophic lateral sclerosis (ALS). LJCR allows prediction of progression as well as identification of subgroups and subgroup-specific model parameters.

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Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis

Cited by 27 publications

References 47 publications

Decreased serum creatinine levels predict short survival in amyotrophic lateral sclerosis

Decreased serum creatinine levels predict short survival in amyotrophic lateral sclerosis

Increased Cerebrospinal Fluid Adenosine 5'-triphosphate in Patients with Amyotrophic Lateral Sclerosis

Penalized longitudinal mixed models with latent group structure, with an application in neurodegenerative diseases

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