Protein-Energy Kaybinin Etyolojisinde Beslenmenin, Renal Replasman Tedavisinin ve Inflamasyonun Rolu

Transkript

1 28. TSN Ulusal Nefroloji, Hipertansiyon, Diyaliz ve Transplantasyon Kongresi Protein-Energy Kaybinin Etyolojisinde Beslenmenin, Renal Replasman Tedavisinin ve Inflamasyonun Rolu T. Alp Ikizler, MD Professor, Medicine Vanderbilt University Medical Center

2 Schematic representation of causes and manifestations of PEW in Kidney Disease ISRNM Position Paper - Kidney International

3 Simplified flow schedule of uremia and its complications Picture stolen from P. Stenvinkel who stole it from Anders Alvestrand

4 Uremik Protein Energy Kaybina Hedefli yaklasim Dialytic Factors Inadequate Nutrient Intake Other Factors Bioincompatibility Inadequate Dose of Dialysis Nutrient Losses Increased Energy Expenditure Protein-Energy Wasting Co-morbidities Inflammation, DM Frequent Hospitalizations Metabolic & Hormonal Derangements

5 Uremik Ultrafiltrate ve Agizdan Besin (Protein) Alimi Ingested Protein (ml) ml 1 ml 2 ml 4 ml Urine Ultrafiltrate 1-5 kda Modified from Anderstam, Mamoun & Bergstrom JASN 1996

6 Dietary Protein Intake and Daily Creatinine Excretion During Progression of Renal Disease 1,4 1,2 1 0,8 0,6 0,4 0,2 0 > < 10 Dietary protein intake g/kg/d Creatinine Clearance ml/min Creatinine excretion g/d Ikizler JASN 1995

7 Hemodializ Hastalarinin Istah Durumu Self-reported appetite status % of patients 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 37% 31% 25% 7% 0% Very good Good Fair Poor Very poor Normal Appetite Diminished Appetite

8 Hemodiyalize bağlı Net Katabolizma ve Diyaliz Esnasinda Protein Kaybi Membranların biyokimyasal yapısı HD membranları ile ilişkili kompleman aktivasyonu ile birlikte protein katabolizmasında artış Gutierrez & Bergstrom Kidney Int 1990 Membran porlarının boyutu Hemodiyaliz sırasında amino asit kaybı (? Daha geniş porlardan daha yüksek kayıplar) Wolfson & Kopple Kidney Int 1989 Ikizler & Hakim Kidney Int 1994

9 Dializ Esnasinda Onlenemez Amino Acid Kaybi: Degisik Dializorlerin Etkisi total g/dialysis CU PMMA PS PD/Day Ikizler & Hakim 1994 Kidney Int

10 Arterial Plasma Essential Amino Acids (µmol/l) Arterial Plasma Total Amino Acids (µmol/l) * * 15% * * 20% % % B D PD 0 B D PD Ikizler et al, AJP, 2002

11 Hemodializ e Bagli Net Tum-Vucut Protein Kaybi proteolysis synthesis net balance (mg/kgffm/min) * * 10% 11% 96% * B D PD 21% * Ikizler et al, AJP, 2002

12 Plazma arteriyel aminoasit konstantrasyonlari Intradialytik Nutrusyon ile artmaktadir Total AA Esansiyel olmayan Esansiyel AA Dallı zincirli AA (µmol/l) µmol/l p<0.05 Control Pre HD During HD Post HD µmol/l p<0.05 IDPN Pre HD During HD Post HD Pupim et al, JCI, 2002

13 Schematic representation of causes and manifestations of PEW in Kidney Disease ISRNM Position Paper - Kidney International Inflammation

14 Prevalence of malnutrition, inflammation and atherosclerosis in predialysis patients Malnutrition 44% Inflammation 32% 53% with inflammation 32% 72% with malnutrition N = 109 Carotid plaque 72% Stenvinkel et al. Kidney Int 1999

15 SDB Hastalarinda Inflamasyona Yol Acan Sebepler Uremic Toxins Loss of Kidney Function Oxidative Stress Insulin Resistance INFLAMMATION Co-Morbidities Renal Replacement Therapy Atherosclerosis Infections Endotoxin Vascular Access Diabetes Mellitus Bioincompatibility

16 Inflammation is Associated with Loss of Kidney Function IL-6 (pg/ml) CTL (N=50) baseline (N=50) 3 months (N=50) 6 months (N=46) 9 months (N=41) 12 months (N=41) Pupim, Himmelfarb, Ikizler Kidney int 2004

17 Inflammatory Signals Associated With Hemodialysis IL-6 (pg/ml) Fibrinogen FSR (%/day) * δ * δ * 58% 68% 14% 34% B D PD Caglar, Pupim, Ikizler, KI, 2002

18 Hemodializ e Bagli Net Tum-Vucut Protein Kaybi Inflamasyon un katkisi proteolysis synthesis net balance (mg/kgffm/min) * * 10% 96% 11% * B D PD 21% * Ikizler et al, AJP, 2002

19 Systemic Inflammatory Response Syndrome Tissue Injury Activation of IL-1, TNF, IL-6 Activation of other cytokines Biological activities Acute phase response CRP, Albumin, SAA

20 Metabolic Effects of Inflammation MUSCLE LOSS ANOREXIA COMPLEMENT ACTIVATION INFLAMMATION UREMIA INCREASED REE FEVER APP SYNTHESIS INCREASED SNS ACTIVITY IMMUNE SYSTEM MODULATION

21 Continuous IL-1 Infusion Leads to Decreased Food Intake Ling et al JCI 1996

22 Serum Interleukin-6 and Appetite in 331 Hemodialysis Patients Logarithm of Serum Interleukin-6 (pg/ml) Normal Appetite very good Diminished Appetite ANOVA p=0.004* (*logarithmic scale) Kalantar-Zadeh et al, Am J Clinal Nutrition, fair poor good Reported Appetite Scales (1: very good, 2: good; 3: fair; 4: poor) Mean ±0.95 Conf. Interval

23 Potential Pharmacological Strategies Using Inflammation and Oxidative Stress as a Target Statins Tocopherols Randomized double-blind placebo controlled trial 57 HD-pts completed the study 8 weeks 308 mg γ-tocopherol and 800 mg docosahexaenoic acid (DHA) Journal of Renal Nutrition 2007

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25 IL-1 Beta Inhibition Improves Chronic Inflammation in Hemodialysis Patients Hung & Ikizler et al JASN 2010 in press

26 IL-1 Beta Inhibition Improves Chronic Inflammation in Hemodialysis Patients 53% 1% 40% 20% Hung, Ikizler JASN Mar;22(3):437-42

27 Nutritional Biomarkers at Baseline and Post Intervention by Randomization Group Prealbumin, mg/dl Albumin, g/dl Lean Body, gm IL-1ra Placebo Hung, Ikizler JASN Mar;22(3):437-42

28 (Üremik) Protein Enerji Kaybı Sendromu Üremik protein enerji kaybı sendromunun etiyolojisi multifaktoriyeldir. diyetin azalması + HD ilişkili katabolizma + Inflamasyon + Insulin resistance -> tükenme -> mortalite ve morbiditede Nutrisyonel müdahaleler -> uygun ve emniyetli; IDPN veoral besinler HD ilişkili katabolizması parsiyel olarak geri döndürebilir (primer olarak aminoasit havuzunu yeniden doldurarak)

29 Metabolic Paradigm for Uremic Wasting and Treatment Options IDN PPAR-γ Agonist Insulin DM/GI Anti-inflammatory agent Modified from O Sullivan, AJ, JJ Kelley. Kidney International 2007(71);

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