A 2012 update on inflammatory cytokines and adipokines: Revelance for CKD

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EURECA-m CME COURSE Cardiovascular Problems

September 7-8, 2-012, Ankara-Turkey A 2012

Endocrinology and Metabolic Diseases Medical

1 EURECA-m CME COURSE Cardiovascular Problems and Solutions in Chronic Kidney Disease September 7-8, 2-012, Ankara-Turkey A 2012 update on inflammatory cytokines and adipokines: Revelance for CKD Prof. Andrzej Więcek Department of Nephrology, Endocrinology and Metabolic Diseases Medical University of Silesia, Katowice, Poland awiecek@spskm.katowice.pl

2 Prevalence of obesity in the USA and in Europe In USA: the age-adjusted prevalence of obesity (BMI 30 kg/m 2 ) was 33.8% overall, 32.2% among men, and 35.5% among women the corresponding prevalence estimates for overweight and obesity combined (BMI 25) were 68.0%, 72.3% and 64.1% Flegal K et al. JAMA. 2010; 303: In Europe: the prevalence of obesity (BMI 30 kg/m 2 ) in men ranged from 4.0% to 28.3% and in women from 6.2% to 36.5% Berghöfer A et al. BMC Public Health. 2008; 8: 200

3 Prevalence of obesity in Poland Obesity (BMI > 30 kg/m 2 ) Zdrojewski T. et al., NATPOL III Study, 2011

Obese female mammoth ivory figurine produced at least 35000 calender years ago (Aurignacien

4 Obese female mammoth ivory figurine produced at least calender years ago (Aurignacien period) and found in the Hohler Fels cave in southwestern Germany Conard D.J, Nature, 2009, 459,

5 Obesity in the Paleolithic era The Venus of Willendorf is a superbly crafted sculpture of a naked obese woman from the stone age Colman M.D. E. Endocr Pract. 1998, 4: 58-59

6 Body-Mass Index and mortality among 1.46 million white adults x Estimated Hazard Rati for death from any cause according to BMI for all study participants and for healthy subjects who never smoked de Gonzales et al. N. Eng. J. Med. 2010; 363:

7 Adjusted relative risk for end-stage renal disease (ESRD) by body mass index (BMI) Model adjusted for multiphasic health checkup period, age, sex, race, education level, smoking status, history of myocardial infarction, serum cholesterol level, proteinuria, haematuria and serum creatinine evel. Hsu et al. Ann Intern Med. 2006; 144: 21 28

8 Distribution of body mass index (BMI) in dialysis patients (based on USRDS) Zoccali C., Mallamaci F.,J. Internal Med., 2011, 269,

9 White adipose tissue in the lean and obese state Adipocytes are shown with yellow triglyceride droplets and blue cytoplasm. In the lean state the light blue cytoplasm represent a state of normoxia, whereas the dark blue in the obese state represents a hypoxic state. Pre adipocytes are shown in brown, macrophages in green, blood vessels/endothelial cells in red, and the extracellular matrix as black. Lean state Obese state Halberg N et al. Endocrinol Metab Clin North Am. 2008; 37: 753

10 Cardiovascular and reologic effects, sleep apnea Renal effects Activation of the sympathetic nervous system Metabolic effects (dyslipidemia, carbohydrate intolerance) Endocrine effects (hyperinsulinism, insulin resistance, hypercortisolism, increased erythropoietin secretion) Increased coagulation/decreased fibrinolysis ( PAI) Haematologic effects NF B PAI Leptin Adiponectin TNF Angiotensin Resistin Adipocytes Obesity Więcek A. et al., Nephrol. Dial. Transplant. 2002; 17;

11 Więcek A. et al. Nephrol. Dial. Transplant. 2007, 22:

12 The major physiological functions of adipose tissue secretory products in 2012 Adamczak M., Wiecek A., Sem. Nephrol., 2012, in press

13 Relationship between body fat mass and plasma adipocytokine levels Shoji T et al.: Metabolism 2005; 54:

14 Effects of peripheral hormones on hypothalamic regulation of food intake and energy expenditure + CKD Engineer D.R., Garcia J.M., Intern. J. Peptides, 2012, ID

15 Markers of appetite regulation in various cachectic states

16 Leptin a new uraemic toxin? or Leptin marker of nutrition?

18 (BMI) Plasma leptin and CRP concentration at baseline and 12 months after initialion of HD therapy

19 Leptin is a marker of nutrition: 1. Postive correlation with fat tissue: a) low BMI = low serum leptin concentation b) caloric suplemenation increases body fat mass and median serum leptin concentration 2. Markedly elevated serum leptin concentration does not suppress appetite in uraemic patients (leptin resistance). Uraemia is characterised by relative resistance to many hormones (PTH, HGH, Insulin) and cytokines: a) Serum leptin increses and serum CRP decreases in those HD patiens who gain weight after 12 months after initiation of HD treatment

20 Circulating adiponectin concentrations ADIPONECTIN Scherer Ph. E., Diabetes, 2006, 55,

21 Relationship between body fat mass and plasma adipocytokine levels Shoji T et al.: Metabolism 2005; 54:

22 Circulating forms of adiponectin Adamczak M., Chudek J., Wiecek A., Sem. Dial., 2009, 22,

23 Adiponectin multimerization three major forms of adiponectin found in circulation Scherer Ph. E., Diabetes, 2006, 55,

24 Adiponectin, adiponectin receptors and intracellular signalling Hui X. et al., Brit. J. Pharmacol., 2012, 165,

25 The pleiotropic role of adiponectin in the cardiovascular system Hui X. et al., Brit. J. Pharmacol., 2012, 165,

26 lipids accumulation in monocyte derived PDGF-BB FGF TNF-α glucose macrophages HB EGF utilization transformation of macrophages into foam cells fatty acid oxidation scavenger receptors Adiponectin insulin signalling superoxide glucose uptake VCAM-1 ICAM-1 E-selectin TIMP anti-atherogenic actions NO Więcek A. et al. Nephrol Diali Transplant 2007, 22: gluconeogenesis insulin-sensitizing actions

27 Adiponectin synthesis and biodegradation in patients with chronic kidney disease Adamczak M., Chudek J., Wiecek A., Sem. Dial., 2009, 22,

28 Adipokines and HOMA-IR in non-obese PD patients HOMA-IR is inversly correlated with plasma adiponectin concentration in PD patients Yoo D.E. et al. Endocrine J., 2012 in press

29 Plasma adiponectin concentration and insulin, HDL, CRP levels, and LVMI in hemodialysis patients Abdallah E. et al. Kidney Blood Pres. Res., 2012, 35,

30 Survival curves for analysis of time to cardiovacular events in hemodialysis patients Group 1. Adiponectin <15.1 ug/ml Group 2. Adiponectin > 15.1 ug/ml p< Abdallah E. et al. Kidney Blood Pres. Res., 2012, 35,

31 Kaplan-Meier survival curves for cardiovascular events (fatal and nonfatal) in patients witch chronic renal failure ADPN ADPN ADPN Zoccali C. et al., J. Am. Soc. Nephrol., 2002, 13,

32 Interventions known to increase adiponectin levels Barseghian A. et al. J Am Coll Cardiol. 2011,57,

33 Perivascular white adipose tissue (pwat) as a paracrine regulator of inflammation and atherosclerosis Juge-Aubry C.E. et al., Best Practice Res., Clin. Endocrinol. Metab., 2005, 19,

34 The adipose renin-angiotensin system Dorresteijn J.A.N. et al., Obesity Rev. 2012, 13, 17-26

35 Physiologic/pathophysiologic significance of an adipocyte renin-angiotensin system Thacher S et al. Mol Cell Endocrinol. 2009; 29:

36 Obesity associated adipocyte dysfunction contributes to hypertension by endocrine and paracrine effects of adipokines on endothelial cells, VSMCs and macrophages Zhou J. and Qin G., Am. J. Cardiovacular Dis., 2012, 2,

37 Ehrhart-Bornstein M et al.: Proc Natl Acad Sci U S A. 2003; 100:

38 Relationship between visceral obesity and both sald dependend hypertesion and chronic kidney disease Fujita T. Nephrol. Dial. Transplant., 2007; 22:

39 Adiponectin inhibits permeability across a podocyte monolayer Ahima R. J. Clin. Invest. 2008, 118:

40 Role of leptin and adiponectin in glomerulopathies Mathew et al., Cur. Diab. Rev., 2011,7, 41-49,

41 Bone metabolism regulated by adipocytes, osteoblast and osteocalcin Cao J.J., J. Orthopedic Surg. Res., 2011, 6,30

42 Potential mechanisms by which resisitin may mediate cardiovascular dysfunction Jamaluddin M.S. et al., Brit. J. Pharmacol., 2012, 165,

Estimated glomerular filtration rate (egfr) according to quartiles of serum resistin concentrations and the age- and sex-adjusted mean values of serum resistin levels according to egfr Kawamura R et

43 Estimated glomerular filtration rate (egfr) according to quartiles of serum resistin concentrations and the age- and sex-adjusted mean values of serum resistin levels according to egfr Kawamura R et al. Nephrol. Dial. Transplant. 2010;25: The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please journals.permissions@oxfordjournals.org

44 Hospitalization free survival according to the quartiles of serum resistin levels in hemodialysis patients Chung W. et al. J. Korean Med. Sci., 2012, 27,

45 Serum chemerin concentration and egfr in healthy controls, patients with ESRD before and 3 months after kidney transplantation Rutkowski P. et al. Regulatory Peptides, 2012, 173, 55-59

46 Survival curves for all-cause mortality among 252 incident dialysis patients according to the chemerin levels Yamamoto T. et al., Nephrol. Dial. Transplant., 2010, 25,

47 Association between plasma ometin levels and metabolic risks factors Shibata R. et al., Diabetology, Metab. Syndrom, 2012, 4, 2-4

48 Serum omentin 1 levels in normal glucose tolerance group, type 2 diabetes patients without carotid plaque and type 2 diabetes with carotid plaque Yoo H.J. et al. Cardiovacular Diab., 2011,10, 103

49 Serum omentin levels in haemodialysis patients Alcelik A. et al., Kidney Blood Pres. Res., 2012, 35,

50 Conclusions: Adipokines, a 2012 up-date New adipokines have been discovered (e.g. chemerin, ometin) Role of adipokines in pathogenesis of CKD progression, CV co-morbidities and uraemic toxicity was confirmed Still not enough information concerning the therapeutic utilization of this novel information

51 Thank you for very much your attention! Andrzej Wiecek Katowice

52 Plasma visfatin levels and appetite in CKD 5 patients starting dialysis therapy Carrero J.J. et al., Nephrol. Dial. Transplant, 2010, 25,

53 Adipokines as uremic toxins Teta D., J. Renal Nutrition, 2012, 22, 81-85

Obesity and the kidney

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