A 2012 update on inflammatory cytokines and adipokines ... · A 2012 update on inflammatory...
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A 2012 update on inflammatory cytokines and adipokines: Revelance for CKD
EURECA-m CME COURSE Cardiovascular Problems and Solutions
in Chronic Kidney Disease
September 7-8, 2-012, Ankara-Turkey
Prof. Andrzej Więcek
Department of Nephrology, Endocrinology and Metabolic Diseases Medical University of Silesia, Katowice, Poland
e-mail: [email protected]
In USA:
• the age-adjusted prevalence of obesity (BMI≥ 30 kg/m2) 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%
In Europe:
• the prevalence of obesity (BMI≥ 30 kg/m2) in men ranged from 4.0% to 28.3% and in women from 6.2% to 36.5%
Prevalence of obesity in the USA and in Europe
Flegal K et al. JAMA. 2010; 303: 235-241
Berghöfer A et al. BMC Public Health. 2008; 8: 200
Prevalence of obesity in Poland
Zdrojewski T. et al., NATPOL III Study, 2011
Obesity (BMI > 30 kg/m2)
Obese female mammoth ivory figurine produced at least 35000 calender years ago (Aurignacien period) and found
in the „Hohler Fels” cave in southwestern Germany
Conard D.J, Nature, 2009, 459, 248-252
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
x
Body-Mass Index and mortality among 1.46 million white adults
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: 2211-9
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
Distribution of body mass index (BMI) in dialysis patients (based on USRDS)
Zoccali C., Mallamaci F.,J. Internal Med., 2011, 269, 407-409
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.
Halberg N et al. Endocrinol Metab Clin North Am. 2008; 37: 753
Lean state Obese state
Więcek A. et al., Nephrol. Dial. Transplant. 2002; 17; 194-195
• 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
↑NFB
↑PAI ↑Leptin ↓Adiponectin ↑TNF ↑Angiotensin ↑Resistin
Adipocytes
Obesity
The major physiological functions of adipose tissue secretory products in 2012
Adamczak M., Wiecek A., Sem. Nephrol., 2012, in press
Shoji T et al.: Metabolism 2005; 54: 330-334
Relationship between body fat mass and plasma adipocytokine levels
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 287457
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
Shoji T et al.: Metabolism 2005; 54: 330-334
Relationship between body fat mass and plasma adipocytokine levels
Adiponectin multimerization – three major forms of adiponectin found in circulation
Scherer Ph. E., Diabetes, 2006, 55, 1537-1545
Adiponectin, adiponectin receptors and intracellular signalling
Hui X. et al., Brit. J. Pharmacol., 2012, 165, 574-590
The pleiotropic role of adiponectin in the cardiovascular system
Hui X. et al., Brit. J. Pharmacol., 2012, 165, 574-590
Adiponectin ↓scavenger
receptors
↑NO ↑TIMP
↓VCAM-1
↓ ICAM-1
↓ E-selectin
↓TNF-α
↓ lipids accumulation
in monocyte derived
macrophages
↓transformation of
macrophages into
foam cells
↓superoxide
↓PDGF-BB
↓FGF
↓HB EGF
↑ glucose
utilization
↑fatty acid
oxidation
↑insulin
signalling
↑glucose
uptake
↓gluconeogenesis
anti-atherogenic actions insulin-sensitizing actions Więcek A. et al. Nephrol Diali Transplant 2007, 22:981-988
Adiponectin synthesis and biodegradation in patients with chronic kidney disease
Adamczak M., Chudek J., Wiecek A., Sem. Dial., 2009, 22, 391-395
Adipokines and HOMA-IR in non-obese PD patients
Yoo D.E. et al. Endocrine J., 2012 in press
HOMA-IR is inversly correlated with plasma adiponectin concentration in PD patients
Plasma adiponectin concentration and insulin, HDL, CRP levels, and LVMI in hemodialysis patients
Abdallah E. et al. Kidney Blood Pres. Res., 2012, 35, 247-253
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< 0.0412
Abdallah E. et al. Kidney Blood Pres. Res., 2012, 35, 247-253
Kaplan-Meier survival curves for cardiovascular events
(fatal and nonfatal) in patients witch chronic renal failure
Zoccali C. et al., J. Am. Soc. Nephrol., 2002, 13, 134-141
ADPN
ADPN
ADPN
Interventions known to increase adiponectin levels
Barseghian A. et al. J Am Coll Cardiol. 2011 ,57, 761-70
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, 547-566
Physiologic/pathophysiologic significance of an adipocyte renin-angiotensin system
Thacher S et al. Mol Cell Endocrinol. 2009; 29: 111–117
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, 143-149
Fujita T. Nephrol. Dial. Transplant., 2007; 22: 3102-3107
Relationship between visceral obesity and both sald dependend hypertesion and chronic kidney disease
Adiponectin inhibits permeability across a podocyte monolayer
Ahima R. J. Clin. Invest. 2008, 118:1619–1622
Bone metabolism regulated by adipocytes, osteoblast and osteocalcin
Cao J.J., J. Orthopedic Surg. Res., 2011, 6,30
Potential mechanisms by which resisitin may mediate cardiovascular dysfunction
Jamaluddin M.S. et al., Brit. J. Pharmacol., 2012, 165, 622-632
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;25:3236-3240
© The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: [email protected]
Hospitalization free survival according to the quartiles of serum resistin levels in hemodialysis patients
Chung W. et al. J. Korean Med. Sci., 2012, 27, 377-388
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
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, 4017-4023
Association between plasma ometin levels and metabolic risks factors
Shibata R. et al., Diabetology, Metab. Syndrom, 2012, 4, 2-4
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
Serum omentin levels in haemodialysis patients
Alcelik A. et al., Kidney Blood Pres. Res., 2012, 35, 511-516
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
Plasma visfatin levels and appetite in CKD 5 patients starting dialysis therapy
Carrero J.J. et al., Nephrol. Dial. Transplant, 2010, 25, 901-906