Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine

A population-based study

Adriano Chiò, Andrea Calvo, Giacomo Bovio, Antonio Canosa, Davide Bertuzzo, Francesco Galmozzi, Paolo Cugnasco, Marinella Clerico, Stefania De Mercanti, Enrica Bersano, Stefania Cammarosano, Antonio Ilardi, Umberto Manera, Cristina Moglia, Riccardo Sideri, Kalliopi Marinou, Edo Bottacchi, Fabrizio Pisano, Roberto Cantello, Letizia Mazzini & 1 others Gabriele Mora

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

IMPORTANCE: There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials. OBJECTIVES: To correlate several hematological markers evaluated at diagnosis with ALS outcome in a population-based series of patients (discovery cohort) and replicate the findings in an independent validation cohort from an ALS tertiary center. DESIGN, SETTING, AND PARTICIPANTS: The discovery cohort included 712 patients with ALS from the Piemonte and Valle d'Aosta Register for Amyotrophic Lateral Sclerosis from January 1, 2007, to December 31, 2011. The validation cohort comprised 122 patients with ALS at different stages of disease consecutively seen at an ALS tertiary center between January 1, 2007, and January 1, 2009. MAIN OUTCOMES AND MEASURES: The following hematological factorswere investigated and correlated with survival: total leukocytes, neutrophils, lymphocytes, monocytes, glucose, creatinine, uric acid, albumin, bilirubin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatine kinase, thyroid-stimulating hormones, and erythrocyte sedimentation rate; all analyses were performed separately by sex. The patient of the validation cohort also underwent bioelectrical impedance analysis for the calculation of fat-free mass. RESULT: Of the 712 patients in the examined period in Piemonte and Valle d'Aosta, 638 (89.6%) were included in the study. Only serum albumin (men: ≤4.3 vs >4.3mg/dL, P <.001; women: ≤4.3 vs >4.3mg/dL, P <.001) and creatinine levels (men: ≤0.82 vs >0.82mg/dL, P = .004; women: 0.05mg/dL, P = .004) and lymphocyte count (men: 1700/μL, P = .04; women: ≤1700 vs >1700/μL, P = .02) were significantly associated with ALS outcome in both sexes with a dose-response effect (better survival with increasing levels). These findings were confirmed in the validation cohort. Multivariable analysis showed that serum albumin (men: hazard ratio [HR], 1.39; 95% CI, 1.05-1.90; P = .02; women: HR, 1.73; 95% CI, 1.35-2.39; P = .001) and creatinine (men: HR, 1.47; 95% CI, 1.11-1.95; P = .007; women: HR, 1.49; 95% CI, 1.07-2.05; P = .02) were independent predictors of survival in both sexes; no other hematological factor was retained in the model. In patients with ALS, serum albumin was correlated with markers of inflammatory state while serum creatinine was correlated with fat-free mass, which is a marker of muscle mass. CONCLUSIONS AND RELEVANCE: In ALS, serum albumin and creatinine are independent markers of outcome in both sexes. Creatinine reflects the muscle waste whereas albumin is connected with inflammatory state. Both creatinine and albumin are reliable markers of the severity of clinical status in patients with ALS and can be used in defining prognosis at the time of diagnosis.

Original languageEnglish
Pages (from-to)1134-1142
Number of pages9
JournalJAMA Neurology
Volume71
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

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Amyotrophic Lateral Sclerosis
Albumins
Creatinine
Outcome Assessment (Health Care)
Population
Serum Albumin
Survival
Biomarkers
Fats
Muscles
Blood Sedimentation
Lymphocyte Count
Thyrotropin
Creatine Kinase
Uric Acid
Electric Impedance
Bilirubin
LDL Cholesterol
HDL Cholesterol
Monocytes

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology
  • Medicine(all)

Cite this

Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine : A population-based study. / Chiò, Adriano; Calvo, Andrea; Bovio, Giacomo; Canosa, Antonio; Bertuzzo, Davide; Galmozzi, Francesco; Cugnasco, Paolo; Clerico, Marinella; De Mercanti, Stefania; Bersano, Enrica; Cammarosano, Stefania; Ilardi, Antonio; Manera, Umberto; Moglia, Cristina; Sideri, Riccardo; Marinou, Kalliopi; Bottacchi, Edo; Pisano, Fabrizio; Cantello, Roberto; Mazzini, Letizia; Mora, Gabriele.

In: JAMA Neurology, Vol. 71, No. 9, 01.09.2014, p. 1134-1142.

Research output: Contribution to journalArticle

Chiò, A, Calvo, A, Bovio, G, Canosa, A, Bertuzzo, D, Galmozzi, F, Cugnasco, P, Clerico, M, De Mercanti, S, Bersano, E, Cammarosano, S, Ilardi, A, Manera, U, Moglia, C, Sideri, R, Marinou, K, Bottacchi, E, Pisano, F, Cantello, R, Mazzini, L & Mora, G 2014, 'Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine: A population-based study', JAMA Neurology, vol. 71, no. 9, pp. 1134-1142. https://doi.org/10.1001/jamaneurol.2014.1129
Chiò, Adriano ; Calvo, Andrea ; Bovio, Giacomo ; Canosa, Antonio ; Bertuzzo, Davide ; Galmozzi, Francesco ; Cugnasco, Paolo ; Clerico, Marinella ; De Mercanti, Stefania ; Bersano, Enrica ; Cammarosano, Stefania ; Ilardi, Antonio ; Manera, Umberto ; Moglia, Cristina ; Sideri, Riccardo ; Marinou, Kalliopi ; Bottacchi, Edo ; Pisano, Fabrizio ; Cantello, Roberto ; Mazzini, Letizia ; Mora, Gabriele. / Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine : A population-based study. In: JAMA Neurology. 2014 ; Vol. 71, No. 9. pp. 1134-1142.
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abstract = "IMPORTANCE: There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials. OBJECTIVES: To correlate several hematological markers evaluated at diagnosis with ALS outcome in a population-based series of patients (discovery cohort) and replicate the findings in an independent validation cohort from an ALS tertiary center. DESIGN, SETTING, AND PARTICIPANTS: The discovery cohort included 712 patients with ALS from the Piemonte and Valle d'Aosta Register for Amyotrophic Lateral Sclerosis from January 1, 2007, to December 31, 2011. The validation cohort comprised 122 patients with ALS at different stages of disease consecutively seen at an ALS tertiary center between January 1, 2007, and January 1, 2009. MAIN OUTCOMES AND MEASURES: The following hematological factorswere investigated and correlated with survival: total leukocytes, neutrophils, lymphocytes, monocytes, glucose, creatinine, uric acid, albumin, bilirubin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatine kinase, thyroid-stimulating hormones, and erythrocyte sedimentation rate; all analyses were performed separately by sex. The patient of the validation cohort also underwent bioelectrical impedance analysis for the calculation of fat-free mass. RESULT: Of the 712 patients in the examined period in Piemonte and Valle d'Aosta, 638 (89.6{\%}) were included in the study. Only serum albumin (men: ≤4.3 vs >4.3mg/dL, P <.001; women: ≤4.3 vs >4.3mg/dL, P <.001) and creatinine levels (men: ≤0.82 vs >0.82mg/dL, P = .004; women: 0.05mg/dL, P = .004) and lymphocyte count (men: 1700/μL, P = .04; women: ≤1700 vs >1700/μL, P = .02) were significantly associated with ALS outcome in both sexes with a dose-response effect (better survival with increasing levels). These findings were confirmed in the validation cohort. Multivariable analysis showed that serum albumin (men: hazard ratio [HR], 1.39; 95{\%} CI, 1.05-1.90; P = .02; women: HR, 1.73; 95{\%} CI, 1.35-2.39; P = .001) and creatinine (men: HR, 1.47; 95{\%} CI, 1.11-1.95; P = .007; women: HR, 1.49; 95{\%} CI, 1.07-2.05; P = .02) were independent predictors of survival in both sexes; no other hematological factor was retained in the model. In patients with ALS, serum albumin was correlated with markers of inflammatory state while serum creatinine was correlated with fat-free mass, which is a marker of muscle mass. CONCLUSIONS AND RELEVANCE: In ALS, serum albumin and creatinine are independent markers of outcome in both sexes. Creatinine reflects the muscle waste whereas albumin is connected with inflammatory state. Both creatinine and albumin are reliable markers of the severity of clinical status in patients with ALS and can be used in defining prognosis at the time of diagnosis.",
author = "Adriano Chi{\`o} and Andrea Calvo and Giacomo Bovio and Antonio Canosa and Davide Bertuzzo and Francesco Galmozzi and Paolo Cugnasco and Marinella Clerico and {De Mercanti}, Stefania and Enrica Bersano and Stefania Cammarosano and Antonio Ilardi and Umberto Manera and Cristina Moglia and Riccardo Sideri and Kalliopi Marinou and Edo Bottacchi and Fabrizio Pisano and Roberto Cantello and Letizia Mazzini and Gabriele Mora",
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TY - JOUR

T1 - Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine

T2 - A population-based study

AU - Chiò, Adriano

AU - Calvo, Andrea

AU - Bovio, Giacomo

AU - Canosa, Antonio

AU - Bertuzzo, Davide

AU - Galmozzi, Francesco

AU - Cugnasco, Paolo

AU - Clerico, Marinella

AU - De Mercanti, Stefania

AU - Bersano, Enrica

AU - Cammarosano, Stefania

AU - Ilardi, Antonio

AU - Manera, Umberto

AU - Moglia, Cristina

AU - Sideri, Riccardo

AU - Marinou, Kalliopi

AU - Bottacchi, Edo

AU - Pisano, Fabrizio

AU - Cantello, Roberto

AU - Mazzini, Letizia

AU - Mora, Gabriele

PY - 2014/9/1

Y1 - 2014/9/1

N2 - IMPORTANCE: There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials. OBJECTIVES: To correlate several hematological markers evaluated at diagnosis with ALS outcome in a population-based series of patients (discovery cohort) and replicate the findings in an independent validation cohort from an ALS tertiary center. DESIGN, SETTING, AND PARTICIPANTS: The discovery cohort included 712 patients with ALS from the Piemonte and Valle d'Aosta Register for Amyotrophic Lateral Sclerosis from January 1, 2007, to December 31, 2011. The validation cohort comprised 122 patients with ALS at different stages of disease consecutively seen at an ALS tertiary center between January 1, 2007, and January 1, 2009. MAIN OUTCOMES AND MEASURES: The following hematological factorswere investigated and correlated with survival: total leukocytes, neutrophils, lymphocytes, monocytes, glucose, creatinine, uric acid, albumin, bilirubin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatine kinase, thyroid-stimulating hormones, and erythrocyte sedimentation rate; all analyses were performed separately by sex. The patient of the validation cohort also underwent bioelectrical impedance analysis for the calculation of fat-free mass. RESULT: Of the 712 patients in the examined period in Piemonte and Valle d'Aosta, 638 (89.6%) were included in the study. Only serum albumin (men: ≤4.3 vs >4.3mg/dL, P <.001; women: ≤4.3 vs >4.3mg/dL, P <.001) and creatinine levels (men: ≤0.82 vs >0.82mg/dL, P = .004; women: 0.05mg/dL, P = .004) and lymphocyte count (men: 1700/μL, P = .04; women: ≤1700 vs >1700/μL, P = .02) were significantly associated with ALS outcome in both sexes with a dose-response effect (better survival with increasing levels). These findings were confirmed in the validation cohort. Multivariable analysis showed that serum albumin (men: hazard ratio [HR], 1.39; 95% CI, 1.05-1.90; P = .02; women: HR, 1.73; 95% CI, 1.35-2.39; P = .001) and creatinine (men: HR, 1.47; 95% CI, 1.11-1.95; P = .007; women: HR, 1.49; 95% CI, 1.07-2.05; P = .02) were independent predictors of survival in both sexes; no other hematological factor was retained in the model. In patients with ALS, serum albumin was correlated with markers of inflammatory state while serum creatinine was correlated with fat-free mass, which is a marker of muscle mass. CONCLUSIONS AND RELEVANCE: In ALS, serum albumin and creatinine are independent markers of outcome in both sexes. Creatinine reflects the muscle waste whereas albumin is connected with inflammatory state. Both creatinine and albumin are reliable markers of the severity of clinical status in patients with ALS and can be used in defining prognosis at the time of diagnosis.

AB - IMPORTANCE: There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials. OBJECTIVES: To correlate several hematological markers evaluated at diagnosis with ALS outcome in a population-based series of patients (discovery cohort) and replicate the findings in an independent validation cohort from an ALS tertiary center. DESIGN, SETTING, AND PARTICIPANTS: The discovery cohort included 712 patients with ALS from the Piemonte and Valle d'Aosta Register for Amyotrophic Lateral Sclerosis from January 1, 2007, to December 31, 2011. The validation cohort comprised 122 patients with ALS at different stages of disease consecutively seen at an ALS tertiary center between January 1, 2007, and January 1, 2009. MAIN OUTCOMES AND MEASURES: The following hematological factorswere investigated and correlated with survival: total leukocytes, neutrophils, lymphocytes, monocytes, glucose, creatinine, uric acid, albumin, bilirubin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatine kinase, thyroid-stimulating hormones, and erythrocyte sedimentation rate; all analyses were performed separately by sex. The patient of the validation cohort also underwent bioelectrical impedance analysis for the calculation of fat-free mass. RESULT: Of the 712 patients in the examined period in Piemonte and Valle d'Aosta, 638 (89.6%) were included in the study. Only serum albumin (men: ≤4.3 vs >4.3mg/dL, P <.001; women: ≤4.3 vs >4.3mg/dL, P <.001) and creatinine levels (men: ≤0.82 vs >0.82mg/dL, P = .004; women: 0.05mg/dL, P = .004) and lymphocyte count (men: 1700/μL, P = .04; women: ≤1700 vs >1700/μL, P = .02) were significantly associated with ALS outcome in both sexes with a dose-response effect (better survival with increasing levels). These findings were confirmed in the validation cohort. Multivariable analysis showed that serum albumin (men: hazard ratio [HR], 1.39; 95% CI, 1.05-1.90; P = .02; women: HR, 1.73; 95% CI, 1.35-2.39; P = .001) and creatinine (men: HR, 1.47; 95% CI, 1.11-1.95; P = .007; women: HR, 1.49; 95% CI, 1.07-2.05; P = .02) were independent predictors of survival in both sexes; no other hematological factor was retained in the model. In patients with ALS, serum albumin was correlated with markers of inflammatory state while serum creatinine was correlated with fat-free mass, which is a marker of muscle mass. CONCLUSIONS AND RELEVANCE: In ALS, serum albumin and creatinine are independent markers of outcome in both sexes. Creatinine reflects the muscle waste whereas albumin is connected with inflammatory state. Both creatinine and albumin are reliable markers of the severity of clinical status in patients with ALS and can be used in defining prognosis at the time of diagnosis.

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