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Role of Protein-Energy Status, Frailty and Skeletal Muscle Wasting in Progressive (CKD)

This presentation highlights the importance of protein-energy status, frailty, and skeletal muscle wasting in progressive CKD. It discusses the diagnostic criteria for frailty and protein-energy wasting, as well as structural alterations in skeletal muscle in CKD. The presentation also explores the effects of interventions such as nandrolone decanoate and exercise training on skeletal muscle. Additionally, it addresses the impact of frailty treatment on clinical outcomes in CKD patients.

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Role of Protein-Energy Status, Frailty and Skeletal Muscle Wasting in Progressive (CKD)

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  1. Role of Protein-Energy Status, Frailty and Skeletal Muscle Wasting in Progressive (CKD) Joel D. Kopple, MD Chennai, India December 11, 2018 Division Nephrology & Hypertension, LA Biomedical Research Institute at Harbor-UCLA Medical Biomedical RCenter, David Geffen School of Medicine at UCLA, UCLA Fielding School of Public Health Conflicts of Interest: Affix Health,, Dr. Schar, Shire, Chugai Pharmaceuticals, Nephroceuticals

  2. Goals for Presentation • Define and Skeletal Muscle (SKM) WastinProtein-Energy Wasting (PEW), Frailty g in CKD. 2.Provide evidence that these three syndromes often occur relatively early in the the course of CKD. 3. Describe potential ways to prevent or mitigate these disorders.

  3. A Common Diagnostic Criterion for Frailty* Presence of 3 or more of the following: Unintentional weight loss Self-reported exhaustion Measured weakness Slow walking speed Low physical activity _______________________________________ *Fried et al J Gerontol A Biol Sci Med Sci 2001;56:M146-M156

  4. Prevalence of Frailty and Its Various Components at Different Stages of CKD Wilhelm-Leen et al Am J Medicine 2009;122:664-671

  5. Protein-Energy Wasting Protein-energy wasting (PEW) is defined as the loss of somatic and circulating body protein and energy reserves. The term PEW is used rather than protein-energy malnutrition because some causes of PEW are unrelated to inadequate nutrient intake.

  6. Criteria for Diagnosis of Protein-Energy Wasting (PEW) in Patients with AKI or CKD For the diagnosis of PEW in AKI or CKD, at least one finding in 3 of these 4 categories must be present. Optimally, these characteristics should be identified on at least 3 occasions preferably 2-4 weeks apart and cannot be extraneous; ie, due to nephrosis, medicines lowering cholesterol, amputations. Fouque et al Kid Int 2008;73:391-398

  7. STRUCTURAL ALTERATIONS OF SKELETAL MUSCLE IN CKF • Fiber atrophy predominantly of type IIx/IIb fibers. • Myofibers exhibit whorling, inclusion bodies, excessive subsarcolemmal and intermyofilamental glycogen aggregation end marked myofilamental loss. • Mitochondria may be swollen, disrupted, pleomorphic and transverse with excessive subsarcolemmal mitochondrial clusters. • Reduced activities of aerobic enzymes, lowered levels of contractile proteins (myosin heavy chains). • Decreased capillarity with a low capillary:myofiber ratio.

  8. No RxNDExTxND+ExTx EFFECT OF NANDROLONE DECANOATE (ND) & EXERCISE TRAINING (ExTx) ON SKM Johansen et al JASN 2006;17:2307

  9. Roshanvaran et al. JASN 2013;24:822-830

  10. Higher Muscle Quality (i.e., Hand Grip Strength Divided by Arm Lean Mass) is Associated with Survival in 272 MHD Patients Independent of Age, Diabetes Mellitus or Serum Albumin Yoda et al. Biomedicine Phamcotherapy 2012;66:266-270

  11. When in the Course of Progressive CKD Does PEW, Frailty or SKM Wasting Start to Emerge?

  12. Relationship Between GFR and Protein and Energy Intake in 1760 CKD Patients Undergoing Screening for the MDRD Study Kopple et al. Kidney Int 2000;57:1688

  13. Relation of GFR & Protein & Energy Intake in 1760 CKD Patients Screened for MDRD Study Kopple et al

  14. KNOW-CKD Study in Non-Dialyzed CKD 1-5 Patients Hyun et al. J Korean Med Sci 2017; 32:257-263

  15. KNOW-CKD Study Involving 1834 South Korean CKD Patients: Cross–Sectional Study Hyun et al. J Korean Med Sci 2017; 32:257-263

  16. Relation Between Changes in eGFR and Changes Weight and BMI in 3933 People with CKD in the CRIC Study (Panels A-D) and 1067 People with in CKD in the AASK Study (Panels E F). E Ku et al Am J Kidney Dis 2018;

  17. E Ku et al Am J Kidney Dis 2018;

  18. Roshanravan et al AJKD 2012:60:912-921

  19. Randomized Prospective Clinical Trials of Nutritional Treatment of Chronic Dialysis Patients with PEW *Treatment and control groups both received oral nutrition supplements. From Lodebo et al. 2018

  20. Table 2. Non-Randomized Studies Evaluating Nutritional Support for Dialysis patients with PEW From Lodebo et al. 2018

  21. Frailty in CKD What About the Treatment of Frailty? Will It Improve Clinical Outcome in CKD Patients?

  22. Treatment of Frailty on Clinical Outcomes (1) • Few studies of Frailty treatment in people with CKD or ESKD. • Anabolic agents (testosterone, IGF-1, carnitine) may improve protein balance in ESKD patients. 3. Several studies report growth hormone increases in N balance, serum albumin, lean body mass, muscle mass, and/or strength in adult dialysis patients (Garriboto 1997, Johannsson 1999, Hansen 2000, Kopple 2005, Feldt-Rasmussen 2007).

  23. Treatment of Frailty on Clinical Outcomes (2) 4. Exercise training in CKD patients and other populations increases exercise capacity and quality of life but has not been specifically tested in frail CKD patients. • The effects of these interventions on morbidity or mortality in CKD or ESKD patients have not been tested.

  24. FRAILTY, PEW & SKM WASTING in CKD & CHRONIC DIALYSIS PATIENTS: KEY POINTS (1) • All are common in CKD and Chronic Dialysis Patients • All are strongly associated with increased morbidity and mortality • Increased incidence of PEW and SKM Wasting begins when eGFR is as high as 30-40 mL/min/1.73m2

  25. PEW AND FRAILTY: KEY POINTS (2) Protein- Energy Wasting (PEW) & Frailty in CKD & Chronic Dialysis (CD) Patients: 4. Treatment often improves measures of PEW (nutritional support) and possibly Frailty and SKM Wasting (exercise training, anabolic agents?). 5. More research will be necessary to determine whether prevention or treatment of PEW or Frailty will improve Morbidity, Mortality or Quality of Life.

  26. The End

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