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Creatinine and C-reactive protein in amyotrophic lateral sclerosis, multiple sclerosis and Parkinson's disease.

ABSTRACT: Serum creatinine and C-reactive protein have been proposed as potential biomarkers for neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis and Parkinson's disease. However, longitudinal studies investigating temporal patterns of these biomarkers, including the phase before diagnosis, are rare. We performed a case-control study including all newly diagnosed patients with amyotrophic lateral sclerosis (N?=?525), multiple sclerosis (N?=?1815) or Parkinson's disease (N?=?3797) during 2006-2013 in Stockholm, Sweden, who participated in the Stockholm CREAtinine Measurements (SCREAM) project. For each case, we randomly selected up to five controls from SCREAM that were individually matched to the case by age, sex and county of residence (N?=?2625 for amyotrophic lateral sclerosis, N?=?9063 for multiple sclerosis and 18?960 for Parkinson's disease). We collected for both the cases and the controls testing results of serum creatinine and C-reactive protein performed by healthcare providers in Stockholm during the study period. Median levels of creatinine and C-reactive protein were visualized using locally weighted smoothing curves among cases and controls. A linear mixed model was also applied to explore temporal changes within an individual. Compared to controls, patients with amyotrophic lateral sclerosis had lower levels of creatinine from 2?years before diagnosis onwards. In contrast, patients with amyotrophic lateral sclerosis had lower levels of C-reactive protein before diagnosis but higher levels after diagnosis, compared to controls. Focusing the 2?years before to 2?years after diagnosis, patients with amyotrophic lateral sclerosis displayed statistically significantly decreasing level of creatinine from 1?year before diagnosis until 2?years after diagnosis, whereas increasing level of C-reactive protein from diagnosis until 2?years after diagnosis. There were no similar patterns noted among patients with multiple sclerosis or Parkinson's disease, or the controls of the three patient groups. Patients with amyotrophic lateral sclerosis display distinct temporal patterns of creatinine and C-reactive protein before and after diagnosis, compared to amyotrophic lateral sclerosis-free controls or patients with multiple sclerosis and Parkinson's disease.

SUBMITTER: Cui C

PROVIDER: S-EPMC7850290 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Creatinine and C-reactive protein in amyotrophic lateral sclerosis, multiple sclerosis and Parkinson's disease.

Cui Can C Sun Jiangwei J Pawitan Yudi Y Piehl Fredrik F Chen Honglei H Ingre Caroline C Wirdefeldt Karin K Evans Marie M Andersson John J Carrero Juan-Jesus JJ Fang Fang F

Brain communications 20200918 2

Serum creatinine and C-reactive protein have been proposed as potential biomarkers for neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis and Parkinson's disease. However, longitudinal studies investigating temporal patterns of these biomarkers, including the phase before diagnosis, are rare. We performed a case-control study including all newly diagnosed patients with amyotrophic lateral sclerosis (<i>N</i> = 525), multiple sclerosis (<i>N</i> = 1815) or Par ...[more]

PMID: 33543134

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Project description:Importance:Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. Objective:To examine the prognostic significance of CRP in ALS. Design, Setting, and Participants:Patients' serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. Main Outcomes and Measures:Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. Results:A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale-Revised, at first evaluation (r?=?-0.14818; P?=?.004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P?=?.007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P???.001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with elevated baseline CRP levels receiving the higher dose of NP001 had significantly less functional impairment after the treatment period compared with patients with normal baseline CRP, regardless of whether patients with normal CRP levels received NP001 or placebo (3.00 [3.62] vs -7.31 [6.23]; P?=?.04). Conclusions and Relevance:These findings suggest that patients with ALS and elevated serum CRP levels progress more rapidly than do those with lower CRP levels and that this elevation may reflect a neuroinflammatory state potentially responsive to the immune regulators such as NP001.

Dataset Information

Creatinine and C-reactive protein in amyotrophic lateral sclerosis, multiple sclerosis and Parkinson's disease.

Publications

Creatinine and C-reactive protein in amyotrophic lateral sclerosis, multiple sclerosis and Parkinson's disease.

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