Download STAGES OF HYPERTENTION

HYPERTENTION AND CKD
YASER EL HENDY MD
STAGES OF HYPERTENTION
• Normal blood pressure. if it's below 120/80 mm Hg.
• Prehypertension. systolic pressure ranging from 120
to 139 mm Hg or a diastolic pressure ranging from 80
to 89 mm Hg.
It tends to get worse over time.
• Stage 1 hypertension. systolic pressure ranging from
140 to 159 mm Hg or a diastolic pressure ranging from
90 to 99 mm Hg.
• Stage 2 hypertension. systolic pressure of 160 mm Hg
or higher or a diastolic pressure of 100 mm Hg or
higher.
JNC7
Epidemiology
• Approximately one in three adults in the
United States has hypertension .
• The prevalence of hypertension is higher
among patients with CKD, progressively
increasing with the severity of CKD.
• It is estimated that hypertension occurs in
23.3% of individuals without CKD,
• 35.8% of stage 1,
• 48.1% of stage 2,
• 59.9% of stage 3,
• 84.1% of stage 4-5 CKD patients
Hypertension and Progression of CKD
Bakris et al. American Journal of Kidney Diseases, Vol 36, No 3
(September), 2000: pp 646-661
Defining “CKD”
GFR < 60 mL/min/1.73 m2 for ≥ 3 months with
or without kidney damage.
Kidney damage for ≥ 3 months manifest by
either
 Pathologic abnormalities, or
 Markers of kidney damage,
Defining “Kidney Damage”
 Markers of Kidney Damage
Proteinuria
Microalbuminuria
Hematuria (especially when seen with proteinuria)
Casts especially with cellular elemen
Defining “Kidney Damage”
 Pathologic Abnormalities?
 By Radiology (US, CT, MR, etc)--e.g.
 Multiple cysts consistent with PKD
 Extensive scarring
 Small kidneys
 By Histology -- renal biopsy
Prevalence of CKD: NHANES 1999-2004
CKD 5
0.4%
CKD 4
CKD 3
5.4%
CKD 2
5.4%
CKD 1
5.7%
Total
16.8%
n=12,785
MMWR Morb Mortal Wkly Rep. 56:161; 2007
• Hypertension is a major risk factor for
cardiovascular and renal disease.
Who should we screen?
How should we screen?
15
• Conversely, chronic kidney disease (CKD) is the
most common form of secondary
hypertension
PATHOPHYSIOLOGY
• Prevalence of hypertension also varies with
the cause of CKD
• strong association with hypertension was
reported in patients with,
renal artery stenosis (93%)
diabetic nephropathy (87%)
polycystic kidney disease (74%)
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Pathophysiological Processes Leading to
Albuminuria and Glomerular Lesions
Dyslipidaemia
Hypertension
Diabètes
Smoking
INCREASE AG II
Oxidative stress
Increase in intra glomular
Endothelial dysfunction
pressure
NO, local mediators, RAAS (Ang II)
Vasoconstriction
Thrombosis
Inflammation Plaque rupture
Vascular lesion
and remodelling
Adapted from Dzau. Hypertension 2001;37:1047–52
The Renal Continuum
Endothelial
dysfunction
Microalbuminuria
Proteinuria
Early Intervention
Adapted from Dzau and Braunwald. Am Heart J 1991;121:1244–63
End-stage
renal disease
• Despite the high prevalence of hypertension
and availability of effective medications, only
a minority of patients achieve recommended
treatment goals.
• However, in the last decad awareness and
control of hypertension have improved from
69% to 80% and 27% to 50%, respectively
Hypertension in Egypt
Hypertension is a major health problem
in Egypt with a prevalence rate of
26.3% population (> 25 years)
Only 8% of hypertensive Egyptians have their
blood pressure controlled
among the adult
1- Ibrahim MM, Rizk H, Apple LJ, et al. For the NHP investigation team. Hypertension, prevalence, awareness, treatment and control in Egypt. .
23 | Presentation Title | Presenter Name | Date | Subject | Business Use Only
Approximately 70% of Patients* in Europe Do
Not Reach BP Goal
BP goal achieved
Patients (%)
100
BP goal not achieved
60
79
70
81
72
England
Sweden
Germany
Spain
Italy
80
60
40
20
0
*Treated for hypertension
BP goal is <140/90 mmHg
Wolf-Maier et al. Hypertension 2004;43:10–17
Poor Compliance and Persistence with Antihypertensive
Treatment
Continuous antihypertensive
use beyond first year (%)
100
Among patients receiving therapy after the first year,
~50% stop therapy within the next 2 years
Men
Women
80
Retrospective, cohort study of
community pharmacy records (n=2,325)
60
40
20
0
1
2
3
4
Years after first prescription
5
6
7
8
9
10
Van Wijk et al. J Hypertens 2005;23:2101–7
Treatment of Hypertension in CKD
• Treatment Goals
• Delay progression of CKD
• Minimize complications of HTN
• Generally requires multimodality treatment
The Patient with early stage CKD is 5 to 10
times more likely to die from a
cardiovascular event than progress to ESRD.
Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW, Collins AJ. Chronic kidney
disease and the risk for cardiovascular disease, renal replacement, and death in the United
States Medicare population, 1998 to 1999. J Am Soc Nephrol 2005; 16:489-95.
CKD Patients Are More Likely to Die than
to Progress to ESRD
GFR 15-29
Died
RRT
Event Free
Disenrolled
GFR 30-59
GFR 60-89; + Proteinuria
5 year follow-up
GFR 60-89, No Proteinuria
N=27998
0% 20 40 60 80 100
% % % % %
Keith, et al, Arch Int Med; 2004; 164:659-663
Correlation between decline in kidney function (estimated
by GFR) and increasing incidence of CV complications &
death from CV disease
GFR (mL/min/1.73 m2):Blue > 75.0; Yellow 60.0–74.9; Green 45.0–59.9; Purple < 45
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Initiation of Anti Hypertensive
Treatment
JNC VII and ESH-ESC Summary: Target
BP Goals
Type of hypertension
Uncomplicated
BP goal (mmHg)
<140/90
Complicated
Diabetes mellitus
<130/80
Kidney disease
<130/80
Chobanian et al. JAMA 2003;289:256072
Guidelines Committee. J Hypertens 2003;21:101153
CONTINUED ON NEXT SLIDE
33
CONTINUED FROM PREVIOUS SLIDE
34
2013 updated JNC 8 guidelines
• Two key recommendations in the JNC 8 guidelines that
differ from the JNC 7 guidelines are
• (1) less aggressive targeting of (BPs) and treatmentinitiation thresholds for elderly patients and for those
younger than age 60 years with diabetes and kidney
disease
• (2) no longer recommending only thiazide-type
diuretics as the initial therapy in most patients
(angiotensin-converting enzyme [ACE] inhibitors,
angiotensin receptor blockers [ARBs], calcium channel
blockers [CCBs], or diuretics are recommended)
PULMONARY RENAL
SYNDROME
YASER EL HENDY
PROFESSORE OF INTERNAL MEDICINE
Lifestyle modifications
• Weight loss helps to prevent hypertension
(range of approximate systolic BP reduction
[SBP], 5-20 mm Hg per 10 kg)
• DASH (Dietary Approaches to Stop HTN) diet (
SBP reduction, 8-14 mm Hg)
which is rich in fruits and vegetables and
encourages the use of fat-free or low-fat milk
and milk products
• Limit alcohol intake to no more than 1 oz (30 mL)
of ethanol per day for men
• 24 oz [720 mL] of beer,
• 10 oz [300 mL] of wine,
• 2 oz [60 mL] of 100-proof whiskey,
• 0.5 oz (15 mL) of ethanol per day for women and
people of lighter weight
• range of approximate SBP reduction, 2-4 mm Hg
• Reduce sodium intake to no more than 100
mmol/d (2.4 g sodium or 6 g sodium chloride;
range of approximate SBP reduction, 2-8 mm
Hg)
• Maintain adequate intake of dietary
potassium (approximately 90 mmol/d)
• Maintain adequate intake of dietary calcium
and magnesium
• Stop smoking
• Engage in aerobic exercise at least 30 minutes
daily for most days SBP reduction, 4-9 mm Hg
RAAS modulation: ACEI and ARB pathways
Bradykinin/NO
ANGIOTENSIN I
Vasodilation
Tissue protection
Chymase
tPA
Cathepsin
ACEI
Inactive fragments
ANGIOTENSIN II
“Angiotensin II
escape”
ARB
AT1 RECEPTOR
AT2 RECEPTOR
Vasoconstriction
Na/H2O retention
Sympathetic activation
Cell growth
Mediates apoptosis
Vasodilation
Natriuresis
Tissue regeneration
Anti-proliferation
NO = nitric oxide
Adapted from Dzau V. J Hypertens. 2005;23(suppl I):S9-17.
Interventions that delay progression
of CKD: ACEI and ARBs
• Mechanisms
– Lower systemic blood pressure
– Lower glomerular capillary blood pressure and
protein filtration
– Reduce AT II mediated cell proliferation and
fibrosis
Should be employed in all proteinuric
kidney diseases!
ARBs vs ACEI
• ARB: Specific selective blockade AT1-receptor
• ARB: Blocks also non-ACE produced AII
• ARB: Stimulation of the AT2-receptor
• ARB: No systemic increase bradykinin
• ARB: Fewer side-effects and no serious or fatal side-effects
ARBs decrease renal complications in T2DM
T2DM (N)
Treatment
IRMA-2
Microalbuminuria
(590)
Time to nephropathy:
Irbesartan
150/300 mg vs 39% (150 mg, P = 0.08)
placebo
70% (300 mg, P < 0.001)
IDNT
Nephropathy
(1715)
Irbesartan/
amlodipine/
placebo
ESRD/ Cr 2/mortality:
20% vs placebo (P = 0.02)
23% vs amlodipine (P = 0.006)
MARVAL
Microalbuminuria
(332)
Valsartan/
amlodipine
 UAER at 24 weeks:
44% valsartan vs 8% amlodipine
(P < 0.001)
RENAAL
Nephropathy
(1513)
Losartan/
placebo
ESRD/Cr 2 /all deaths:
16% vs placebo (P = 0.02)
Cr = creatinine
UAER = urinary albumin excretion rate
Primary outcome
Adapted from Sharma AM. Hypertension. 2004;44:12-19.
Nondihydropyridine CCBs
• Diltiazem/verapamil decrease glomerular injury
• May have beneficial effects on proteinuria similar
to ACEIs
• Generally 2nd line when ACEIs or ARBs not
tolerated
Dworkin LD, Benstein JA, Parker M, Tolbert E, Feiner HD. Calcium antagonists and converting enzyme inhibitors reduce renal injury by different
mechanisms. Kidney Int 1993;43:808–814.
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Epstein M. Effects of ACE inhibitors and calcium antagonists on progression of chronic renal disease. Blood Press Suppl 1995;2:108–112.
Antihypertensives: Others
• Diuretics commonly used to treat fluid
overload & HTN; no compelling data to
suggest renal protection
• Can use central & peripherally acting
antihypertensive agents in CKD patients
• B blockers consider dose reductions for renal
impairment
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Combination Therapy
ESH/ESC guidelines states that :
• SPC is preferred for patients compliance
• Diuretic with an ACEi or ARB or CCB,
• CCB with an ACEi or ARB
• The ARB/CCB combination appears to be rational and
effective.
These are the combinations recommended for priority use.
DIALYZABLE ANTIHYPERTENSIVE
MEDICATIONS
Percent Removal of Antihypertensive Drugs with
Dialysis
ACE Inhibitors
HD
PD
Benazepril
30%
?
Enalapril
35%
?
Fosinopril
2%
?
Lisinopril
50%
?
Ramipril
30%
?
Angiotensin
Receptor
Blockers
Losartan
HD
PD
None
None
Cardesartan
None
?
Eprosartan
None
None
Telmisartan
None
?
Valsartan
None
None
Irbesartan
None
None
Calcium
Channel
Blockers
Amlodipine
HD
PD
?
?
Diltiazem
30%
?
Nifedipine
Low
Low
Nicardipine
?
?
Felodipine
?
?
Verapamil
Low
Yes
ß-Blockrs
HD
PD
Atenolol
75%
53%
Alebutolol
70%
50%
Carvedilol
None
None
Labetalol
<1%
<1%
Metoprolol
High
?
Antiadrenergie
Drugs
Clonidine
HD
PD
5%
?
Guanabenz
None
None
Methyldopa
60%
30-40%
CONCLUSION
• HTN is a major risk factor for CVD and CKD
• CKD is common cause of secondery HTN
• Both CKD and HTN carry a major health and economic
burden
• Early management may delay the progression of CKD
• Bl P goal is 140\90 in CKD 130\80 in CKD with
proteinuria
• ACE ,ARBS are the drugs of choise in controling HTN
• Close monitoring of bl p and side effect of medication
is necessary
THANK YOU