Appetite stimulation in dialysis patients Anne Marie Liles, PharmD, BCPS

Disclosures I have nothing to disclose

Objectives Describe the morbidity/mortality due to malnutrition in patients with Chronic Kidney Disease (CKD). Identify drug and non-drug treatments of malnutrition in dialysis patients. Describe the approach to treatment of malnutrition in patients on dialysis.

Definitions Nutritional status = assessment of visceral and muscle protein stores and energy balances Protein energy wasting (PEW) = metabolic and nutritional derangements Cachexia = severe form of PEW Ikizler TA. Optimal nutrition in hemodialysis patients. Adv Chronic Kidney Dis. 2013 March; 20 (2): 181-189. Ebner N, et al. Mechanism and novel therapeutic approaches to wasting in chronic disease. Maturitas 2013; 75: 199-206.

Epidemiology of PEW What is the prevalence of PEW in patients receiving dialysis? A. 20% B. 30% C. 40% D. 60%

Prevalence ranges from 20-60% Epidemiology of PEW Prevalence ranges from 20-60% Ikizler TA. Optimal nutrition in hemodialysis patients. Adv Chronic Kidney Dis. 2013 March; 20 (2): 181-189.

Causes of PEW Protein-Energy Wasting Inadequate Nutrient Intake dose of dialysis Co-morbidities, Inflammation Protein-Energy Wasting Nutrient losses Frequent hospitalizations Metabolic and hormonal derangements Increased energy expenditure Insulin resistance/ deprivation Ikizler TA. Optimal nutrition in hemodialysis patients. Adv Chronic Kidney Dis. 2013 March; 20 (2): 181-189.

Protein Energy Wasting of CKD Consequences of PEW Protein Energy Wasting of CKD ↑ hospitalizations ↑ mortality Ikizler TA, Cano NJ, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 2013; 84: 1096-1107.

Lopes AA, et al. Nephrol Dial Transplant 2007; 22(12): 3538-3546. Consequences of PEW ↓ Survival Carrero JJ, et al. Am J Clin Nutr 2007 Mar; 85(3): 695-701. ↑Hospitalization Lopes AA, et al. Nephrol Dial Transplant 2007; 22(12): 3538-3546.

Prevention of PEW Repeated nutritional counseling Optimize renal replacement therapy (RRT) prescriptions Optimize nutrient intake Manage comorbidities Metabolic acidosis Diabetes Inflammatory conditions Heart failure Depression http://www.barnesjewish.org/wellaware-fitness-center/nutritional-counseling Ikizler TA, Cano NJ, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 2013; 84: 1096-1107.

When to Initiate Treatment Poor appetite or poor oral intake ↓ Dietary protein intake or dietary energy intake Albumin < 3.8 g/dL or pre-albumin < 28 mg/dL Unintentional weight loss Worsening nutritional markers over time Subjective global assessment (SGA) in PEW range Ikizler TA, Cano NJ, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 2013; 84: 1096-1107.

Start oral nutritional supplements Approach to Treatment Start oral nutritional supplements No improvement or worsening Intensified therapy Alter RRT prescriptions Increase quantity of oral therapy Initiate tube feeding or PEG if indicated Parenteral interventions (intradialytic parenteral nutrition or total parenteral nutrition) Adjunct therapies Anabolic hormones Appetite stimulants Anti-inflammatory interventions Exercise Ikizler TA, Cano NJ, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 2013; 84: 1096-1107.

Disclaimer The medications discussed in this presentation are not FDA approved for appetite stimulation, weight gain, or nutritional improvement in patients with CKD.

Adjunct Therapy What adjunct therapy are your patients taking for PEW? A. Anabolic steroids B. Growth hormone C. Anti-inflammatories

Anabolic Hormones

Growth Hormone Why it may work Benefits Potential disadvantages Resistance to growth hormone → premature decline in body composition Benefits ↑ in lean body mass (LBM) – +2.5kg over 6 months ↓C-reactive protein and homocysteine ↑ HDL cholesterol ↑ transferrin Potential disadvantages Only recommended for short-term use Injectable dosage form Ikizler TA, Cano NJ, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 2013; 84: 1096-1107. Ikizler TA. Optimal nutrition in hemodialysis patients. Adv Chronic Kidney Dis. 2013 March; 20 (2): 181-189. Feldt-Rasmussen B, et al. Growth hormone treatment during hemodialysis in a randomized trial improves nutrition, quality of life, and cardiovascular risk. J Am Soc Nephrol. 2007; 18: 2161-2171.

Anabolic Steroids How they work http://www.sportsci.org/encyc/anabster/anabster.html

Anabolic Steroids Benefits Potential disadvantages ↑ body weight and body mass index (BMI) ↑ mid-arm muscle circumference ↑ total protein and pre- albumin ↑ transferrin Potential disadvantages Virilizing effects in women Cardiomyopathy Hepatocellular carcinoma ↓ HDL Hypercoagulation Irregular menses Testicular atrophy Infertility in men Injectable Limit use to 6 months Ikizler TA, Cano NJ, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 2013; 84: 1096-1107.

Anti-inflammatories

Potential Therapies Pentoxifylline (Trental) + amino acids Blocks inflammatory process Improves protein breakdown Etanercept (Enbrel®) ↑ albumin and pre-albumin Other options Nutritional anti-oxidants Omega-3 fatty acids Vitamin D (cholecalciferol) Herbal products – green tea extract, curcumin, pomegranate juice Ikizler TA, Cano NJ, Franch H, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int 2013; 84: 1096-1107. Ikizler TA. Optimal nutrition in hemodialysis patients. Adv Chronic Kidney Dis. 2013 March; 20 (2): 181-189.

Appetite Stimulants

Appetite Stimulants What appetite stimulants are your patients taking? A. Megestrol Acetate (Megace®) B. Dronabinol (Marinol®) C. Mirtazapine (Remeron®) D. Cyproheptadine

Megestrol Acetate (Megace®) Progestin Available as tablet, oral suspension, and ES oral suspension Common adverse effects Hypertension, rash, hot sweats, weight gain, diarrhea, flatulence, indigestion, nausea, vomiting, insomnia, mood swings impotence Serious adverse effects Adrenal insufficiency, anemia, deep venous thrombosis, pulmonary embolism, thrombophlebitis Precautions Renal impairment - increased risk of toxic reactions Elderly – increased risk of thromboembolic events and possibly death Micormedex®

Dronabinol (Marinol®) Cannabinoid Precautions Dependence Hypotension, hypertension, syncope, or tachycardia may occur May exacerbate mania, depression, or schizophrenia May lower seizure threshold Micromedex®

Mirtazapine (Remeron®) Antidepressant Precautions Suicidal ideation Hyponatremia Seizures Orthostatic hypotension Serotonin syndrome Liver damage Agranulocytosis, neutropenia Renal impairment – start low, go slow Titrate dose upon discontinuation Micromedex®

Cyproheptadine Antihistamine Antiestrogenic properties Precautions Sedation Dizziness Hypotension May be more effective in mild to moderate disease Facts and Comparisons®

Potential Other Options Thalidomide Melatonin Ghrelin Ikizler TA. Optimal nutrition in hemodialysis patients. Adv Chronic Kidney Dis. 2013 March; 20 (2): 181-189.

Appetite stimulation in dialysis patients Anne Marie Liles, PharmD, BCPS annemarieliles@gmail.com