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

2. Disclosures
I have nothing to disclose

3. 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.

4. 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 March; 20 (2):
Ebner N, et al. Mechanism and novel therapeutic approaches to wasting in chronic disease. Maturitas 2013; 75:

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

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

7. 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 March; 20 (2):

8. 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:

9. 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):
↑Hospitalization
Lopes AA, et al. Nephrol Dial Transplant 2007; 22(12):

10. 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
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:

11. 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:

12. 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:

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

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

15. Anabolic Hormones

16. 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:
Ikizler TA. Optimal nutrition in hemodialysis patients. Adv Chronic Kidney Dis March; 20 (2):
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:

17. Anabolic Steroids How they work

18. 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:

19. Anti-inflammatories

20. 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:
Ikizler TA. Optimal nutrition in hemodialysis patients. Adv Chronic Kidney Dis March; 20 (2):

21. Appetite Stimulants

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

23. 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®

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

25. 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®

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

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

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