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Transcript of Obesity mediated hypertension and renal · PDF fileObesity mediated hypertension and renal...
Obesity mediated hypertension and renal
dysfunction
Gergely Bodor
Marion Hervouet
Nicky Honnef
Mariarosaria Malgadi
Julie Robert
Tutor: Pr Alina Parvu
Objectives
1. Introduction
2. Renal structural and functional changes in obesity
3. Role of adipocytes mediators in obesity
4. Renin angiotensin aldosterone system in obesity
5. Sympathetic nervous system in obesity
6. Obesity paradox
7. Conclusion
Limits of BMI: OBESITY = HETEROGENOUS CONDITION
Others markers of obesity:
waist circumference
MRI ,, cumputed tomography imaging, impedence
Overweight and obesity
« abnormal or excessive fat accumulation that may impair health » WHO
BMI = weight / height²
Tchernof A, Després JP 2014
Abdominal obesity
• Expansion of dysfunctional subcutaneous adipose tissue
• Ectopic triglyceride storage
= Risk factors
waist circumference > 102 cm (men)
> 88 cm (women)
Tchernof A, Després JP 2014
Visceral obesity
“ Excess intra-abdominal adipose tissue accumulation”
= main driving force for most of the disorders associated with obesity
Tchernof A, Després JP 2014
CKD = Chronic Kidney Disease
« The presence of reduced kidney function, or kidney damage,
for a period of 3 months or greater »
- Chronicity
- Constant progression
- Systemic consequences
Table 2:
Stage Description eGFR(mL/min/1.73 m2)
1 CKD with normal or increased GFR >90
2 Mild GFR loss 60–89
3 Moderate GFR loss 30–59
4 Severe GFR loss 15–29
5 Kidney failure <15 or dialysis
Garland, J. S. (2014).
MS: metabolic syndrome; HBP: high blood pressure; DM: diabetes mellitus; CVD: cardiovascular disease; CKD: chronic kidney disease.
Mechanisms of CKD in obesity Indirect Hypertension
Diabetes
Direct Hormonal effects
Hemodynamic effects
Fatty kidney
Compression
Na reabsorption
Compensatory mechanism
Increased filtration
Proteinuria
Glomerulosclerosis CKD ESRD
Vasodilatation
Cells, and adipokines of WAT
Preadipocytes Adipocytes Fibroblasts Macrophages Leukocytes Endothel cells
• Resistin • Leptin • Adiponectin • Visfatin
Resistin
• Antagonizes insulin
• Increases Endothelin-1 production
Effects of ET-1: • Vasoconstrictor tone
• Nitric oxide bioavailability
In CKD Endothelial dysfunction GFR
Briffa JF; 2013
TNF-α, IL-6, IL-1B ROS
Renin and Angiotensinogen mRNA
Inflammation Oxydative stress
renal pathology
GFR
Visfatin
Sommer G; 2008
Adiponectin
Effects:
• Cardioprotective: Insulin sensitivity ROS production
• Acivates AMP activated protein kinase
• In podocytes: downregulation of NADPH oxidase
Adiponectin levels are correlated:
• Negatively: Body fat %, Type-2 diabetes, Insulin resistance, Hypertension
• Positively: Albuminuria, CKD, Type-2 diabetes
Sweiss N; 2014
Leptin in the kidneys
ROS, ET-1
TGF-β1 EC matrix expansion
HT,Endothelial dysfunction
glomerulosclerosis
Alix PM; 2014
Inflamation of WAT in obesity
Overstretched adipocytes
TNF-α, IL-6, MCP-1
Systemic subclinical inflammatory response
Angiotensinogen
Aldosterone
Angiotensin I
Angiotensin II
renin
Blood pressure
ENaC and Na/K pump
Arteriolar Vasoconstriction Vascular tone
Na reabsorption
Fluid volume
ACE
Juxtaglomerular cells
Macula densa
Cardio-pulmonar baroreceptor (SNS)
Blood pressure
PHYSIOLOGICALLY
Adipose tissue Production of bioactives molecules
RAAS receptors and components
angiotensinogen Adipose tissue differenciation and proliferation
Blood Pressure
VISCERAL OBESITY
SNS
Aldosterone
Activation of mineralocorticoides and glucocorticoides receptors
RAAS activation
1 Garland (2014) 2 Kurukulasurya (2011)
Obesity First line therapy
• Body weight reduction obesity
- Calorie intake
- Physical exercise
• Not effective in producing long term weight loss
Second line therapy
• pharmacological treatment
• bariatric surgery
(Bidani, 2013; Lambers Heerspink, 2012; XU, 2014)
Pharmacological treatments
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