1/20/2013 CASE SOFTWARE & BOOKS REASSESSMENT OF ACUTE PHASE PROTEINS AS MARKERS OF MALNUTRITION POINTS TO PONDER FACTS ABOUT SERUM ALBUMIN

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1 CASE SOFTWARE & BOOKS REASSESSMENT OF ACUTE PHASE PROTEINS AS MARKERS OF MALNUTRITION All rights reserved. No part of this presentation may be reproduced by any graphic, mechanical, photographic or electronic process, or in the form of phonographic recording or otherwise copied for public or private use without written permission from the publisher. Mary D. Litchford PhD, RD, LDN WHAT REALLY COUNTS AS A MARKER OF NUTRITIONAL STATUS? POINTS TO PONDER 1. Discuss the difference in starvation related malnutrition and inflammatory related malnutrition 2. Explain the relationship between inflammatory stress, inflammatory biomarkers, cachexia and acute phase proteins. 3. Compare the Malnutrition & Inflammation Score to Academy/ASPEN Consensus Statement on characteristics used to identify adult malnutrition. Not everything that can be counted counts and not everything that counts can be counted. --Albert Einstein HISTORIC MEASURES TO ASSESS FOR MALNUTRITION Vs. FACTS ABOUT SERUM ALBUMIN Comprises 75-80% of normal plasma colloid oncotic pressure 50% of protein content in plasma Synthesized by liver About 5% of total albumin is synthesized daily meaning that dietary protein intake has very little impact on albumin NPO for 24 hr synthesis by > 33% 1

2 MAJOR COMPARTMENTS OF BODY FLUIDS FACTS ABOUT SERUM ALBUMIN >50% albumin in extravascular space Rest in vascular and interstitial spaces 2 Major Compartments in body: Intracellular- 2/3 total body water Extracellular- 1/3 body water: 80% interstitial-lymph fluid, 20% plasma Water moves in and out of cells based on concentration of solute- primarily albumin ETIOLOGY OF HYPOALBUMINEMIA Plasma proteins in cells osmotic pressure in capillary fluid from interstitial will not normally return to capillaries edema Loss of protein in urine Loss protein via denuded skin (i.e. burn or wound) Failure to synthesize protein by liver HYPOALBUMINEMIA COMMON WITH Reported in ~ 20% hospital admissions Nephrotic syndrome Hepatic cirrhosis Heart failure Malnutrition End stage cancer Burns Lymphatic blockage Hemodilution ETIOLOGY OF HYPOALBUMINEMIA Serious protein or caloric malnutrition B12 deficiency- need B12 to make methionine; methionine IAA for DAA synthesis capillary permeability Blockage of lymphatic return Inflammatory stress redirects synthesis of albumin HYPOALBUMINEMIA & INFLAMMATION TNF & IL-6 redirect albumin synthesis by: vascular permeability (alb extravascular space) degradation synthesis 2

3 NEGATIVE ACUTE PHASE REACTANTS INFLAMMATORY RESPONSE Chronic Diseaserelated Inflammation Immune Response Proinflammatory Cytokines IL-1b, IL-6, TNF Acute Phase Reactants Inflammatory Biomarker LBM & Wt Acute Phase Reactants T & B cells Norms Suggest Inflammation Albumin g/dl; g/l Pre-albumin Adults: mg/dl; mg/l Transferrin F mg/dl; g/l M mg/dl; g/l Retinol Binding Protein mg/dl; µmol/l Mobilize Nutrients positive negative POSITIVE ACUTE PHASE REACTANTS Inflammatory Biomarker Norms Suggest Inflammation M: ng/ml; mcg/l F: ng/ml; mcg/l levels may be related to inflammation & NOT reflect Fe stores C-Reactive Protein < 1.0 mg/dl; < 10.0 mg/l > 1.0 mg/dl; > 10 mg/l Fibrinogen mg/dl; 2-4 g/l > 400 mg ( malnutrition) D-dimer < ng/ml; < mcg/l > 600 ng/ml; > 600 mcg/l Erythrocyte Sedimentation Rate M: 0-15 mm/hr(0-20 in 50+) F: 0-20 mm/hr(0-30 in 50+) elevated Ferritin SERUM ALBUMIN NUTRITIONAL MARKER OR INFLAMMATORY MARKER??? Kwashiorkor Sx: Edema rates of infection Fatty liver Sparse subcutaneous fat Low albumin Diet: Adequate Kcal, or no Pro SERUM ALBUMIN NUTRITIONAL MARKER OR INFLAMMATORY MARKER??? SERUM ALBUMIN NUTRITIONAL MARKER OR INFLAMMATORY MARKER??? Minnesota Starvation Study, 1944 Marasmus Sx: Severe loss LBM Skeletal appearance Apathetic Listless Normal albumin Diet: Kcal & Pro Kalm L, Semba R. J. Nutr. 2005;135:

4 SERUM ALBUMIN NUTRITIONAL MARKER OR INFLAMMATORY MARKER??? Minnesota Starvation Study, 1944 Parameter BMI Body composition: LBM Fat Serum Albumin Baseline INTERPRETATION OF HYPOALBUMINEMIA Marker of Morbidity & Mortality Sullivan, D. Association between Inflammation Associated Cytokines, Serum Albumins, and Mortality in the Elderly. JAMDA Goldwasser P, Feldman J. Association of serum albumin and mortality risk. J Clin Epidemiol 1997;50(6): Sullivan DH, Roberson PK, Bopp MM. Hypoalbuminemia 3 Months after hospital discharge: Significance for long-term survival. JAGS 2005;53(7): Oduncu,V. The prognostic value of serum albumin levels on admission in patients with acute ST-segment elevation myocardial infarction undergoing a primary percutaneous coronary intervention. Coron Artery Dis 2012 Dec 14 (Epub) 6 mo semi-starvation diet % 29.2% 9.8% 3.1% 4.3 g/dl 3.9 g/dl Kalm L, Semba R. J. Nutr. 2005;135: INTERPRETATION OF HYPOALBUMINEMIA ALBUMIN, SGA & EVALUATION OF PROTEINS STATUS Marker of Inflammation Sullivan, D. Association between Inflammation Associated Cytokines, Serum Albumins, and Mortality in the Elderly. JAMDA Doweiko JP, Nompleggi DJ.The role of albumin in human physiology and pathophysiology, Part III: Albumin and disease states. JPEN 1991;15: Puskarich-May CL, Sullivan DH, Nelson CL, et al. The change in serum protein concentration in response to the stress of total joint surgery: a comparison of older versus younger patients. JAGS1996;44: Hoye RC, Bennett SH, Geelhoed GW, et al. Fluid volume and albumin kinetics occurring with major surgery. JAMA 1972;222(10): Johnson AM. Low levels of plasma proteins: Malnutrition or inflammation? Clin Chem Lab Med 1999;37(2): Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. NEJM1999;340(6): Covinsky, K. Serum Albumin Concentration and Clinical Assessments of Nutritional Status in Hospitalized Older People: Different Sides of Different Coins? JAGS 50: , adults > or = to 70 yrs. Independently measured serum albumin & Subjective Global Assessment (5% wt mild malnutrition, 10% wt severe malnutrition ) 38% of patients with albumin levels 4.0 g/dl or higher were at least moderately malnourished on the SGA 28% of patients with albumin levels lower than 3.0 g/dl were rated as well nourished Data suggests that the ability of either measure to predict the other measure is only marginally better than chance ALBUMIN NUTRITIONAL MARKER IN KIDNEY DISEASE? Principal marker used to identify malnutrition in CKD Assumptions: ALBUMIN NUTRITIONAL MARKER IN KIDNEY DISEASE? Kopple JD. Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study. Kidney Int 52: , 1997 albumin is marker of malnutrition nutrient density of diet albumin improve patient outcomes CKD & dialysis patients have plasma albumin half-lives & Albumin & Malnutrition in CKD MDRD : Kcal + Pro < /=0.56 g/kg Alb > 4 g/dl degradation rates similar to those of healthy individuals Co-morbidities of CKD negatively impact albumin synthesis Hypoalbuminemia Non-dietary factors 4

5 MALNUTRITION INFLAMMATION SCORE MIS Tool contains 2 sections: MALNUTRITION INFLAMMATION SCORE Kalantar-Zadeh K,. Nephrol Dial Transplant (2004) 19: Questions related to medical history 2. Question related to Subjective Global Assessment Tool References: Kalantar-Zadeh K, Kopple JD, Humphreys MH. Comparing Questions specific to medical hx Questions specific to physical exam (SGA criteria) Overall change in dry wt after dialysis NFPA for fat loss outcome predictability of markers of malnutrition-inflammation complex syndrome in hemodialysis patients. Nephrol Dial Transplant (2004) 19: Dietary intake NFPA for muscle wasting GI symptoms BMI Online version MIS: Functional capacity ( nutritionrelated ALDs) Labs 1. Serum albumin 2. TIBC Pisetkul, C. Malnutrition-Inflammation Score Associated with Atherosclerosis, Inflammation and Short-Term Outcome in Hemodialysis Patients J Med Assoc Thai Vol. 93 Suppl Number of years on dialysis ETIOLOGY BASED MALNUTRITION: DEFINITIONS MALNUTRITION INFLAMMATION SCORE VS. ACADEMY/ASPEN CHARACTERISTICS OF MALNUTRITION Nutrition Risk Concern Presence of Inflammation Yes or No NO Starvation-Related Malnutrition Jensen, G JPEN :710 ETIOLOGY BASED MALNUTRITION: DEFINITIONS Nutrition Risk Concern Inflammation: Yes or No Yes Mild to Moderate Degree Yes Marked Inflammatory Response COMPARISON OF MALNUTRITION ASSESSMENT TOOLS Characteristics of Malnutrition Malnutrition Inflammation Score Insufficient Energy Intake Dietary intake Interpretation of Weight Loss Overall change in dry wt after dialysis Loss of Body Fat SGA for fat loss Loss of Muscle Mass SGA for muscle wasting Accumulation of Fluid Grip Strength Not addressed Functional capacity ( nutrition-related ALDs) Additional areas addressed: GI symptoms Chronic Disease-Related Malnutrition Number of years on dialysis BMI Acute Disease or Injury-Related Malnutrition Labs for albumin, TIBC White, J. J Acad Nutr Diet 2012, Kalantar-Zadeh K. Nephrol Dial Transplant Jensen, G JPEN :710 5

6 COMPARISON OF MALNUTRITION ASSESSMENT TOOLS Characteristics of Malnutrition Malnutrition Inflammation Score Specific benchmarks for: Insufficient Energy Intake Interpretation of Weight Loss Specific benchmarks for: Overall change in dry wt after dialysis BMI Nutrition- Focused Physical Assessment for: Loss of Body Fat Loss of Body Muscle Accumulation of Fluid Subjective Assessment for: Dietary intake Fat loss Muscle wasting GI symptoms Manufacturer s Benchmarks for: Grip Strength Subjective Assessment for: Functional capacity (nutrition-related ALDs) Other benchmarks for: Number of years on dialysis Labs for albumin, TIBC White, J. J Acad Nutr Diet 2012, Kalantar-Zadeh K. Nephrol Dial Transplant LOSS OF SUBCUTANEOUS FAT Interosseus Thenar Triceps Biceps Deltoids Trapezius 6

7 REDUCED GRIP STRENGTH Quadriceps Diminished Function: Gastrocnemius Muscle Strength- Dynamometer (Hand grip) EMERGING TOOLS: EMERGING TOOLS: MALNUTRITION & FUNCTIONAL STATUS MALNUTRITION & FUNCTIONAL STATUS Diminished Lower Extremity Function: Repeated Chair Stands Diminished Lower Extremity Function: Walking test Repeated chair stands Standing balance Guralnik JM, A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49:M85-M94 Guralnik JM,. J Gerontol 1994;49:M85-M94 CLINICAL NUTRITION PEARLS EMERGING TOOLS: MALNUTRITION & FUNCTIONAL STATUS Healthcare reform evidence based guidelines Diminished Lower Extremity Function: Standing balance What you learned in school may NOT be consistent with current guidelines Side by side Semi-tandem Tandem One foot balance Albumin was once considered to be a marker of protein status Current research supports use of albumin as a marker of mortality & inflammation Changes in albumin are not sensitive enough to reflect nutritional status Many factors contribute to changes in albumin Use the range of criteria available to assess for malnutrition 7

8 REASSESSMENT OF ACUTE PHASE PROTEINS AS MARKERS OF MALNUTRITION QUESTIONS??? Mary D. Litchford PhD, RD, LDN