Modifiable Risk Factors Associated with Adverse Cardiovascular and Renal Events in Chronic Kidney Di

1
Modifiable Risk Factors Associated with Adverse
Cardiovascular and Renal Events in Chronic Kidney
Disease

• Hypertension
• Albuminuria
• RAAS
• Dyslipidemia
• Anemia

• Smoking
• Glycemia
• Calcium-phosphorus product
• Others

Sarnak et al. Hypertension. 2003421050-1065.
2
Physiology of RAAS
Goodfriend et al. N Engl J Med.
19963341649-1655.
3
Inappropriate RAAS Activation as a Cause of
Impaired Vascular and Metabolic Health
Angiotensin II
Endothelial Dysfunction Vascular Remodeling
Impaired Adipogenesis
Atherosclerosis
Elevated BP
Glucose Intolerance
Brasier et al. Arterioscler Thromb Vasc Biol.
2002221257-1266 Dzau. J Hypertens.
200523(suppl 1)S9-S17 Engeli et al. Int J
Biochem Cell Biol. 200335807-825 Taniyama et
al. Hypertension. 2003431075-1081.
4
Angiotensin II as a Cardiac and Renal Toxin
Angiotensin
Renin
Ang I
Bradykinin
Chymase Cathepsin G Carboxypeptidase
ACEI
Inactive Fragments
Ang II
ARB
AT1R
Reactive O2 Species
Cell Growth
Sympathetic Activation
Aldosterone
Renal Na, H2O Collagen
Vasoconstriction CHF
Cardiac, Vascular, Renal Hypertrophy
Carey et al. Endocr Rev. 200324261-271.
5
Interactions Between RAAS and SNS

• A-II
• Central SNS activation
• Increased NE release
• Renal sympathetic nerves
• Renin release b1
• Vasoconstriction a1
• Na/H20 retention a1
• Vascular remodeling a1

SNS Activity
A-II
renin
NE
SNSsympathetic nervous system
NEnorepinephrine A-IIangiotensin II.
Cody. Am J Cardiol. 1997809J-14J.
6
HOPE ACE Inhibition Reduced Cardiovascular
Events in Chronic Kidney Disease Patients
Placebo
Ramipril
Diabetics
Hypertensives
Events (per 1000 Patient-Years)
lt1.4
?1.4
lt1.4
?1.4
Nondiabetics
Normotensives
lt1.4
?1.4
lt1.4
?1.4
Mann et al. Ann Intern Med. 2001134629-636.
7
ARB Therapy Slows Renal Disease Progression
IDNT
Primary Composite End Point
Irbesartan 300 mg qd
Amlodipine 10 mg qd
Placebo
N1715
After treatment the change in BP was not
significant primary composite end point defined
as a doubling of baseline serum creatinine
concentration or death from any cause.
IDNTIrbesartan Diabetic Nephropathy Trial.
Lewis et al. N Engl J Med. 2001345851-860.
8
ARB (Losartan) Improves Cardiovascular Outcomes
in Type 2 Diabetics The Losartan Intervention
For End Points Study
Lindholm et al. Lancet. 20023591004-1010.
9
Effect of Losartan on Renal FunctionRENAAL
Placebo
Losartan 50 mg qd
RR 16 95 CI, 0.02-0.28, P.02
N1513
After treatment the change in BP was not
significant primary composite end point defined
as time to first event of doubling of serum
creatinine concentration, ESRD, or
death. RENAALReduction of Endpoints in NIDDM
with the Angiotensin II Antagonist
Losartan. Brenner et al. N Engl J Med.
2001345861-869.
10
Effects of ACEI and ARB on Renal
FunctionCOOPERATE
N263
After treatment the change in BP was not
significant end pointdoubling of serum
creatinine or ESRD. COOPERATECombination
treatment of angiotensin-II receptor blocker and
angiotensin-converting enzyme inhibitors in
nondiabetic renal disease. Nakao et al. Lancet.
2003361117-124.
11
Proteinuria Reduction Groups at Month 6 Determine
the Renal Outcome RENAAL
Renal End Point
ESRD
N1513
De Zeeuw et al. Kidney Int. 2004652309-2320.