Clinical Applications: The Role of Biomarkers in Nutritional Assessment Online Training

Welcome to the Role of Biomarkers in Nutritional Assessment Online Training course.  This course provides an overview of nutritional status effects disease and recovery, especially during hospitalization.  It also covers the nutritional biomarkers measured in clinical laboratories and their role in helping manage nutrition status. Select Next to continue. This overview is provided by: Steve Brimmer, PhD. Upon successful completion of this course, you will be able to: State the impact of malnutrition on hospitalized patients   List the tools to assess nutritional status   Recall strengths and weaknesses of the commonly used biomarkers   Select Next to continue. A lack of adequate nourishment Lack of proper nutrition caused by not eating enough of the right things Poor nourishment due to inadequate digestion and/or absorption of nutrients A nutritional imbalance associated with an increased risk of adverse clinical events (increase in morbidity or mortality) American Society for Parenteral and Enteral Nutrition (ASPEN)  2011 Clinical Guidelines “an acute, sub-acute or chronic state of nutrition, in which varying degrees of over-nutrition or under-nutrition with or without inflammatory activity have led to a change in body composition and diminished function” Mueller CJ. et al.  Parenteral and Enteral Nutrition 2011:35(1):16-24. Kaiser, MJ et al. J Am Geriatr. Soc 2010:58:1734-1738. McWhirter, BMJ 308: 1994. Increased Length of Stay More Frequent Complications Prolonged Wound Healing Increased Co-morbidity Increased Mortality Chronic diseases Depression Difficulty eating Lack of interest in the food Radiation or chemotherapy Medication Hyper-metabolic states Pre-term infants Geriatric patients Nutritional Risk Identified (under-nourished) Inflammation present? No Starvation-related malnutrition Yes Degree Mild to Moderate Chronic Disease-related Malnutrition Marked Response Acute Disease-or Injury-related Malnutrition White J et al. JPEN 2012;36:275-283. Improve or prevent deterioration in mental and physical function Reduce frequency and/or severity of  complications Accelerate recovery and shorten convalescence Reduce length of stay (LOS) Length of Stay in Days   Total malnourished LOS: ↓ 2.6 days   Severely malnourished LOS: ↓ 5 days “In the present study, DRG coding of malnutrition cases resulted in a net CPC allowable of $1,223,154, when compared with $1,046,955 for non-coded malnutrition patients. This difference of $176,199 for 196 patients (intervention group) was extrapolated to all 14,200 patients per year in the medical ward…to give rise to a remarkable savings of $12.8 million.”   Somanchi M et al. JPEN. 2011:35:209-216. To identify malnourished patients To improve outcomes significantly To decrease the cost of health care To monitor patient’s progress Mueller C. J. Parenteral and Enteral Nutrition 2011:35(1):16-24. The ABC’s of Nutritional Assessment: Anthropometric Measurements   Biomarkers Clinical Assessment Dietary Evaluation Anthropometric data Unintended weight loss Weight Height Waist Circumference Triceps skin fold thickness Mid-arm muscle circumference Body Mass Index White J et al. JPEN 2012;36:275-283.   Body Mass Index (BMI) is an international standard for assessing nutritional status BMI is calculated as follows:      BMI = Mass (kg) / (Height (m)) ² BMI of 19 – 27 is considered healthy Low BMI is associated with under-nourishment High BMI is associated with obesity Seres DS. Practical Gastroenterology. 2003. Series #8. 30-39. Disease Risk Relative to BMI Classification BMI Risk Underweight <18.5 Increased Normal 18.5-24.9 Normal Overweight 25.0-29.9 Increased Obesity I 30.0-34.9 High Obesity II 35.0-39.9 Very High Obesity III ≥40.0 Extremely High Risk for: Low BMI: anorexia, bulimia, digestive or absorption problems; increased risk for osteoporosis, impaired immune response, infertility Hi BMI: obesity with increased risk for Type 2 diabetes, hypertension, cardiovascular disease Risk related to waist circumference: <102 cm (40”) in men <88 cm (35”) in women If waist circumference is larger, risk is significantly increased   Adapted from: http://www.nhlbi.nih.gov/health/public/heart/obesity/lose_wt/bmi_dis.htm Ideal Characteristics for Nutritional Biomarkers Minimal Non-nutritional Influences Short Half-life Small Total Body Pool Rapid Synthetic Rate Inexpensive and Automated Most Commonly Used Biomarkers: Albumin Prealbumin Retinol Binding Protein Transferrin C-Reactive Protein Banh L. Practical Gastroenterology October 2006, 46-64.   Nutritional Risk Index (MRI)  NRI = (1.519 x ALB) + (41.7 x present weight / usual weight)   Not Malnourished: > 100 Mildly Malnourished: 97.5 to 100 Moderately Malnourished: 83.5 to < 97.5 Severely Malnourished: < 83.5 Where: ALB = Albumin (g/L); Usual weight = stable weight for > 6  months     Prognostic Inflammation and Nutrition Index (PINI)              (CRP) x (AAG)  PINI = ----------------------------                (PA) x (ALB)   Normal: < 1 Low Risk: 1-10 Medium Risk: 11-20 High Risk: 21-30 Life Risk: > 30 Where: CRP = C-reactive Protein (mg/dL) AAG = α-1-Acid glycoprotein (mg/dL) PA = Prealbumin (mg/dL); ALB = Albumin (g/dL)   Banh L. Practical Gastroenterology October 2006, 46-64. Renal Disease Dehydration Inflammation Liver Disease Mears E. Lab Medicine. 2007:38(1):43-47. History: Chief complaint and medical history can raise suspicion for risk of malnutrition and the presence or absence of inflammation Physical examination: Can indicate presence of malnutrition through weight loss or gain, fluid retention, loss of muscle or fat, and  signs of specific nutrient deficiencies   White J et al. JPEN 2012;36:275-283. JCAHO requires screening for nutritional risk within 24 hours of admission Weight change Appetite, ability to chew/swallow, pain when eating Diet history, dietary restrictions Use of vitamin/mineral or other supplements Food allergies/intolerances Medications Nausea/vomiting Bowel habits: diarrhea, constipation Alcohol or drug use Chronic disease affecting use of nutrients Surgical resection or disease of GI tract Level of activity/exercise Kondrup J et al. Clinical Nutrition (2003) 22(4): 415–421. Consensus Statement: Characteristics Recommended for the Identification and Documentation of Adult Malnutrition (Under-nutrition) Minimum of 2 characteristics is necessary for diagnosis of malnutrition: Insufficient energy intake      Weight loss     Loss of muscle mass Loss of subcutaneous fat Fluid accumulation Diminished functional status --  handgrip strength White J et al. JPEN 2012;36:275-283. Food/nutrient intake Information regarding food and nutrient intake should be obtained A modified diet history, 24-hour recall, “calorie counts” and/or prior documentation of periods of inadequate food intake in the patient’s medical record may be used. White J et al. JPEN 2012;36:275-283. Mears E. Lab Medicine. 2007:38(1):43-47. Produced almost entirely in the liver Transports bilirubin, fatty acids, metals, ions, hormones, and drugs Reference interval: 3.6-5.5 g/dL Medical decision point: less than 3.0 g/dL Half-life is ~ 21 days On admission, ~ 20% of patients have hypoalbuminemia Albumin < 2.0 g/dL often indicates poor prognosis1 1 Reinhardt et al., J. Parent Enter Nutr, 1980; 4, 357 – 359.    Mears E. Lab Medicine. 2007:38(1):43-47.   Increased: Dehydration Blood transfusions Albumin administration Decreased: Protein malnutrition Hepatic failure Inflammation Trauma / Post-operative states Nephrotic syndrome Burns Ascites Over-hydration Pregnancy Corticosteroid use Banh L. Practical Gastroenterology October 2006, 46-64. Advantages: Easy and inexpensive to measure Reflects stable nutrition status Marker of chronic disease and severity Covered by reimbursement   Disadvantages: Insensitive to short-term changes Affected by over-hydration and dehydration Affected by non-nutritional factors (e.g. liver disease, inflammation) Often used as therapeutic agent Albumin is a better marker of increased risk of morbidity and mortality than of under-nutrition.   More properly called Transthyretin Produced in the liver Transports thyroid hormones and retinol binding protein Reference interval: 17 to 34 mg/dL Medical decision point: less than 11 mg/dL Half-life ~ 2 days Has a small body pool and high rate of synthesis Mears E. Lab Medicine. 2007:38(1):43-47. Increased*: High-dose corticosteroid therapy Hyperactive adrenal glands High-dose non-steroidal anti-inflammatory medications Hodgkin's disease Kidney failure * not typically used to monitor these conditions   Decreased: Malnutrition Severe or chronic illness (cancer) Hyperthyroidism Liver disease Certain digestive disorders Dialysis Inflammation and infections Pregnancy When both inflammation and malnutrition are present, prealbumin can rapidly fall to very low levels and interpretation is difficult Bahn L. Practical Gastroenterology October 2006, 46-64. Advantages: Excellent sensitivity to nutritional status Useful for classification and triage Not significantly affected by dehydration Cost effective   Disadvantages: Strongly decreased in end-stage liver disease Decreased by infection and inflammation Factors like acute alcoholism, steroid use, and zinc deficiency may impact Preferred marker for Protein Calorie Malnutrition    Bahn L. Practical Gastroenterology October 2006, 46-64.   Disease Prealbumin (mg/dL) No. of Patients Healthy Volunteers 19.4 ± 5.6 87 Secondary Carcinoma 7.2 ± 2.6 15 Alcoholic Hepatitis 8.5 ± 4.3 12 Chronic Active Hepatitis 8.5 ± 7.3 7 Cryptogenic Cirrhosis 10.0 ± 5.0 7 Obstructive Jaundice 11.1 ± 6.3 9 Inflammatory Bowel Disease 19.7 ± 4.0 6 Hutchinson D et al. Clinica Chimica Acta 1981; 114:69-74.   Table results are Mean ± SD; Reference interval:  17-34 mg/dL   Assessment Normal % Mild Malnourished % Severely Malnourished % % Concordance DNA* 40 41 19 Reference SGA 47 40 13 63.6 PINI 36 35 29 63.9 PAB 41 42 17 76.8 RBP 10 44 16 Not reported   DNA = Detailed Nutritional Assessment SGA = Subjective Global Assessment PINI = calculated Prognostic Inflammation and Nutrition Index PAB = Prealbumin RBP = Retinol Binding Protein   PAB had the best concordance with the DNA which improved when PAB was adjusted for inflammation using CRP Devoto G. et al. Clin. Chem. 2006:52(12):2281-85. “In conclusion, our study results indicate that PAB is: Inexpensive and reliable in evaluation of malnutrition in hospitalized patients Particularly in settings where it is difficult to perform a more comprehensive nutritional assessment Further investigation with sequential measurements needed to elucidate complex relationship between PAB and inflammation and to clarify role of PAB in monitoring nutritional interventions.” Devoto G. et al. Clin. Chem. 2006:52(12):2281-85. Prealbumin is a sensitive indicator of inadequate nutrient intake and should be part of an overall assessment program In patients at nutritional risk, prealbumin, assessed twice weekly, can efficiently sensitize physician to the patient’s nutritional status Prealbumin correlates with outcomes and is an accurate predictor of patient recovery “If prealbumin levels are rising, it is likely that at least 65% of protein and energy needs are being provided” “In patients receiving nutritional support, a rise in prealbumin is normally seen within 4 – 8 days.” Beck FK and Rosenthal TC. Am Fam Physician 2002;65:1575-8. Prealbumin Level Risk Level < 5.0 mg/dL Poor prognosis 5.0 – 10.9 mg/dL Significant risk, aggressive nutritional support indicated 11 – 15 mg/dL Increased risk, monitor status bi-weekly 15 – 35 mg/dL Normal Adapted from Beck FK and Rosenthal TC. Am Fam Physician 2002;65:1575-8. Produced in the liver RBP binds and transports retinol (vitamin A) Reference interval: 3.0 – 6.0 mg/dL Medical decision point: 1.6 mg/dL Half-life: 12 hours Catabolized in the kidney    Mears E. Lab Medicine. 2007:38(1):43-47. Increased: Dehydration Chronic renal disease Corticosteroid or NSAID therapy Decreased: Malnutrition Inflammation Severe liver disease Proteinuria Zinc deficiency Banh L. Practical Gastroenterology October 2006, 46-64. Advantages: Very short half-life and small body pool Excellent sensitivity to acute changes in nutrition status Helps "fill in the gaps" when used with prealbumin Less affected by inflammation   Disadvantages: Strongly affected by kidney disease Decreased in end-stage liver disease Needs zinc and Vitamin A to release from liver   Bahn L. Practical Gastroenterology October 2006, 46-64. Produced in the liver Transports iron Reference interval:  200 to 400 mg/dL Medical decision point: less than 150 mg/dL Half-life: 8 -10 days Affected by iron deficiency    Mears E. Lab Medicine. 2007:38(1):43-47. Increased: Iron deficiency Chronic blood loss Dehydration Pregnancy Oral contraceptives Estrogens Decreased: Malnutrition Inflammation Anemia of chronic disease (cancer) Severe liver disease Nephrotic syndrome Uremia Banh L. Practical Gastroenterology October 2006, 46-64. Advantages: Short half-life and small body pool Decreased in severe malnutrition   Disadvantages: Half-life too long to monitor acute change Strongly affected by iron deficiency Decreased by chronic infection or inflammatory disease Depressed in patients with liver disease   Bahn L. Practical Gastroenterology October 2006, 46-64. Commonly used nutritional biomarkers are negative Acute Phase Reactants (APR) Interpretation of biomarker results needs to take presence of inflammation into account Most commonly used biomarker for inflammation is C-Reactive Protein (CRP) Inflammatory Stimulus Cytokine releasing cells   Positive APR: CRP Fibrinogen Ferritin α-1- Antitrypsin Α-2-Macroglobulin   Negative APR: Albumin Transferrin Prealbumin RBP   Produced in the liver Very sensitive Positive Acute Phase Reactant Reference interval:  <5 mg/L Medical decision point: >10 mg/L Used as sensitive and specific marker of inflammation Suggested as marker to indicate if reduced nutritional biomarker concentrations are primarily due to inflammation rather than malnutrition Low prealbumin and/or elevated CRP suggested poorer outcomes In the absence of inflammation, prealbumin correlated well with other nutritional assessments Underlying cause for inflammation may contribute to malnutrition “ Regular measurement of serum prealbumin and CRP may enhance the comprehensive assessment of overall health status in Peritoneal Dialysis patients.  Identification and management of malnutrition and inflammation should improve survival in our patients.”   Fein PA et al. Kidney International. 2003:64:S87–S91. Albumin or prealbumin are useful in patients with  suspected malnutrition syndrome Results must be interpreted with caution due to limited specificity and sensitivity as indicators of nutrition status Since albumin and prealbumin may be reduced by systemic response to injury, disease, or inflammation, low serum albumin or prealbumin may or may not prove to be malnourishment C-reactive protein measurement can help discern whether inflammation is present If C-reactive protein is increased and albumin or prealbumin decreased, then inflammation is likely  a contributing factor.   White J et al. JPEN 2012:36:275-283. Jensen GL et al. JPEN 2012:36:267-274. There is no “sliver bullet” marker Baseline data of several markers is best Trending data of several markers gives the best information regarding monitoring of nutrition therapy   A comprehensive evaluation is needed to define nutrition status, including medical and dietary history, physical examination, anthropometric measurements and laboratory data