Serum Creatinine and Albumin Predict ALS Survival

July 22, 2014

Blood levels of albumin and creatinine are both independent markers of survival in patients with amyotrophic lateral sclerosis (ALS), a new study suggests.

The study, published online in JAMA Neurology on July 21, was conducted by a team led by Adriano Chiò, MD, from the Rita Levi Montalcini Department of Neuroscience, Torino, Italy.

Dr. Chiò commented to Medscape Medical News that these 2 proteins will make good prognostic markers. "They are easy and cheap to measure, and these tests are already widely available and routinely conducted. These 2 simple measurements, which are already part of many clinical examinations, can give us a much more accurate prognosis on how long the patient has to live than we have at the moment."

Objective Measures

He explained that prognosis is evaluated by using functional scales, such as the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised scale (ALSFRS-R) score.

"But these scores are quite subjective; we need objective measures, and levels of creatinine and albumin are absolutely objective," he said. "Our results suggest they have much better sensitivity and specificity than the measures we use at the moment, such as symptom scores."

He also suggested that albumin and creatinine will be useful surrogate markers for clinical trials of new drugs for ALS.

In the current report, the researchers examined data from a registry of 712 patients with ALS in Italy, which measured several hematologic factors at the time of diagnosis. These included 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.

After adjustment for other factors, only serum albumin and creatinine were independently associated with survival. These 2 proteins were both significantly associated with ALS outcome in both sexes, with a dose-response effect (better survival with increasing levels). No other examined hematologic factors were significantly related to survival at multivariable analysis.

These findings were confirmed in an independent validation in 122 patients at different stages of disease consecutively seen at an ALS tertiary center.

They also found that lower albumin and creatinine levels were strongly related to worse clinical function at diagnosis (ALSFRS-R score and forced vital capacity).

Albumin Reflects Inflammation; Creatinine Reflects Muscle Mass

The 2 proteins are reflecting different processes ongoing in ALS. Serum albumin levels appear to be a marker of the inflammatory state, with an increase of cytokines seen in ALS correlating with reduced albumin levels, while serum creatinine levels related to the fat-free mass of patients (ie, the muscle mass).

Dr. Chiò explained that loss of muscle is a more accurate prognostic factor in ALS than body mass index, which relates to the whole weight of the patient. "Our study shows us that creatinine is a good proxy for loss of muscle which is the main event in ALS. It is representing what is happening in the actual disease process," he said.

Dr. Chiò's team is now measuring both albumin and creatinine routinely in all patients with ALS at the time of diagnosis, and using this information as a guide to prognosis. "It may be too early to recommend that this becomes standard practice, as we probably need some prospective data where these proteins are measured at various time points over the course of the disease. But these data will be available soon from other clinical trials," he added.

In the paper, the researchers point out that their original cohort of patients used for the analysis is highly representative of the general ALS population, as it included about 90% of the patients who were diagnosed as having ALS in the study period in the Piemonte and Valle d'Aosta regions of Italy.

They add that the validation cohort consisted of a consecutive series of patients at different clinical stages of ALS from a tertiary center, recruited for a study on lean body mass; these patients had longer disease duration and more severe disease than those of the discovery cohort; and as predicted from the primary findings, they had lower serum albumin and creatinine levels, suggesting the progressive decrease of these hematologic factors during the course of the disease.

"Both creatinine and albumin are reliable and easily detectable blood markers of the severity of motor dysfunction in ALS and could be used in defining patients' prognosis at the time of diagnosis," they conclude. "Longitudinal studies on the variations in serum albumin and creatinine levels and their relationships to clinical status will help determine whether and how these hematological factors vary during the progression of the disease."

This work was in part supported by a grant and the Joint Programme Neurodegenerative Disease Research from the Italian Ministry of Health and a grant from the European Community's Health Seventh Framework Programme.

JAMA Neurol. Published online July 21, 2014. Abstract

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