title: Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine: a population-based study.
abstract: OBJECTIVE
  There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy2Città della Salute e della Scienza, Azienda Ospedaliero Universitaria, Turin, Italy3Neuroscience Institute of Torino, Turin, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy2Città della Salute e della Scienza, Azienda Ospedaliero Universitaria, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.affiliation: Salvatore Maugeri Foundation, Istituto Di Ricovero e Cura a Carattere Scientifico, Scientific Institute of Pavia, Pavia, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bovio
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Canosa
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bertuzzo
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Galmozzi
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cugnasco
authors.affiliation: Department of Biological and Clinical Science, Azienda Ospedaliero Universitaria San Luigi Gonzaga, University of Turin, Orbassano, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Clerico
authors.affiliation: Department of Biological and Clinical Science, Azienda Ospedaliero Universitaria San Luigi Gonzaga, University of Turin, Orbassano, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Mercanti
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Department of Neurology, Azienda Ospedaliero Universitaria Maggiore di Novara, Novara, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bersano
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cammarosano
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ilardi
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Manera
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.affiliation: Salvatore Maugeri Foundation, Istituto Di Ricovero e Cura a Carattere Scientifico, Scientific Institute of Milano, Milano, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sideri
authors.affiliation: Salvatore Maugeri Foundation, Istituto Di Ricovero e Cura a Carattere Scientifico, Scientific Institute of Milano, Milano, Italy.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Marinou
authors.affiliation: Department of Neurology, Azienda Ospedaliera Regionale di Aosta, Azienda Unità Sanitaria Locale Valle d'Aosta, Aosta, Italy.
authors.forename: Edo
authors.initials: E
authors.lastname: Bottacchi
authors.affiliation: Salvatore Maugeri Foundation, Istituto Di Ricovero e Cura a Carattere Scientifico, Scientific Institute of Veruno, Pavia, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pisano
authors.affiliation: Eastern Piedmont University, Department of Neurology, Novara, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cantello
authors.affiliation: Amyotrophic Lateral Sclerosis Center, Department of Neurology, Azienda Ospedaliero Universitaria Maggiore di Novara, Novara, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.affiliation: Salvatore Maugeri Foundation, Istituto Di Ricovero e Cura a Carattere Scientifico, Scientific Institute of Milano, Milano, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000401:mortality / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007558:Italy; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D012709:Serum Albumin; D003404:Creatinine