There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials.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.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.The following hematological factors were 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.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 >4.3 mg/dL, P < .001; women: ≤ 4.3 vs >4.3 mg/dL, P < .001) and creatinine levels (men: ≤ 0.82 vs >0.82 mg/dL, P = .004; women: ≤ 0.65 vs >0.05 mg/dL, P = .004) and lymphocyte count (men: ≤ 1700 vs >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.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.

Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine: a population-based study

CHIO', Adriano;CALVO, Andrea;CANOSA, ANTONIO;BERTUZZO, DAVIDE;CLERICO, Marinella;DE MERCANTI, STEFANIA FEDERICA;MANERA, Umberto;MOGLIA, Cristina;
2014

Abstract

There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials.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.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.The following hematological factors were 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.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 >4.3 mg/dL, P < .001; women: ≤ 4.3 vs >4.3 mg/dL, P < .001) and creatinine levels (men: ≤ 0.82 vs >0.82 mg/dL, P = .004; women: ≤ 0.65 vs >0.05 mg/dL, P = .004) and lymphocyte count (men: ≤ 1700 vs >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.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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http://dx.doi.org/10.1001/jamaneurol.2014.1129
Adult, Aged, Aged; 80 and over, Amyotrophic Lateral Sclerosis; blood/mortality/pathology, Biological Markers; blood, Cohort Studies, Creatinine; blood, Disease Progression, Female, Humans, Italy, Lymphocyte Count, Male, Middle Aged, Outcome Assessment (Health Care), Predictive Value of Tests, Prognosis, Sensitivity and Specificity, Serum Albumin; analysis
A. Chiò;A. Calvo;G. Bovio;A. Canosa;D. Bertuzzo;F. Galmozzi;P. Cugnasco;M. Clerico;S. De Mercanti;E. Bersano;S. Cammarosano;A. Ilardi;U. Manera;C. Moglia;R. Sideri;K. Marinou;E. Bottacchi;F. Pisano;R. Cantello;L. Mazzini;G. Mora; Piemonte;V. d. Register
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/153857
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