Transcript Treatment of Hypertension in Patients on Hemodialysis

Dr. Abdulkareem Alsuwaida
Associate Professor
King Saud University
Hemodialysis Symposium
08-09 February 2014
Al Madinah AlMunawwarah
Prevalence of hypertension in chronic HD pts
(N=65393, mean age 61 yr, mean duration on HD 8 yr)
Iseki et al. Ther Apher Dial 2007;11:183-188
Death Due to Strokes and Heart Disease
Heart
32
16
16
8
Heart deaths
stroke deaths
Stroke
8
4
2
4
2
1
<120 125 135
148
168
120
125
SYSTOLIC BLOOD PRESSURE mm Hg
135 148
168
Unadjusted survival by baseline predialysis systolic BP
Stidley et al. J Am Soc Nephrol 2006;17:513-520
“Reverse-epidemiology”
 Low BP is a consequence of other disease:
 Major CVD
 Malnutrition-inflammation-atherosclerosis complex
 LVD
Mechanism of HTN
Sodium and volume overload.
 Sympathetic nervous system activity
 Inappropriate renin secretion.
 Alteration in endothelin and nitric oxide.
 Erythropoietin therapy.
 Hyperparathyroidism.
 Other:

Uremic toxins, Nocturnal hypoxemia and sleep disturbances
Nephrol Dial Transplant. 2004 May; 19(5):1058-68
Mechanism of HTN
 Hypervolemia is the major factor
 Positive Sodium balance
 Increases intake and decreased excretion
 Achieving DW will control 60% of cases of HTN
 Assessment of DW
Am J Kidney Dis. 1996 Aug; 28(2):257-61
Mechanism of HTN
 Renin inappropriately high for ? etiology.
 Increase vascular resistance
 Increased in sympathetic activity
 Originate from kidneys


Uremic metabolites that activate chemoreceptors within the
kidney
Increase vascular resistance and systemic BP
When and How to measure the BP in dialysis
patients?
 Dialysis Unit: During, Before, or After
 Home BP
 ABPM
When and How to measure the BP
in dialysis patients?
 Predialysis SBP overestimated mean SBP by an average
of 10 mm Hg
 Postdialysis SBP underestimated mean SBP by an
average of 7 mm Hg
 BP reasings over a period of 1 to 2 weeks rather than
isolated readings should be used
Home blood pressure monitoring is of greater prognostic value
than hemodialysis units recordings
Alborzi et al. CJASN 2007;2:1228-1234
When and How to measure the BP
in dialysis patients?
 Interdialytic ABP monitoring best represent BP in
dialysis patients.
 Only method that will show diurnal variation
 Difficult to repeat, Vascular access
 Home BP
Relationship between BP and mortality in
dialysis patients
Luther JM Kidn Int 2008;73:667-668
Target blood pressure?
 Scarcity of evidence
 Pre-dialysis BP < 150/90
 ABPM < 140/85
 Avoid drop of SBP greater than 30 mm Hg or post
dialysis postural hypotension.

Increase mortality and hospitalization
 < 110/60 mm Hg correlates significantly with the risk of
death within 5 years



Kidney Int 2007;71: 454–61.
Kidney Int 2004;66:1212–20.
Am J Kidn Dis. 2005;45
ABPM systolic BP and mortality.
Agarwal R Hypertension. 2010;55:762-768
Management of Hypertension
 Step 1: Lifestyle modifications and control of volume
status with lifestyle modifications.
 Step 2: Control of volume status with dialysis.
 Step 3: Administration of antihypertensive drugs.
Life style modifications
 Body weight:
 'obesity paradox‘

Mainly explained by mal-or undernutrition.
 Low salt intake
 1000 to 1500 mg of sodium/day
 Exercise
Life style modifications
 Tobacco use
 59% more CHF
 68% more PVD
 Mortality 37%

Foley et al. Kidney Int 2003; 63: 1462-7.
Life style modifications
Management of Hypertension
 Control of volume status
 Limit interdialytic weight gain
 a 2.5 kg is associated with a significant increase in BP
 Achieve dry weight
 Frequent dialysis & Longer dialysis time
Agarwal R, et al. Hypertension. 2009 Mar; 53(3):500-7.
Dry Weight
 Criteria to determining DW:
 No marked fall in BP during dialysis.
 No hypertension (predialysis BP at the beginning of
the week <140/90 mm Hg).
 No peripheral edema.
 No pulmonary congestion on chest X-ray.
 Cardiothoracic ratio ≤50% (≤53% in females).
Dry-weight reduction in hypertensive hemodialysis
patients (DRIP): a randomized, controlled trial.
Agarwal R, et al. Hypertension. 2009 Mar; 53(3):500-7.
Antihypertensive drugs
 160/95 mmHg immediate before the next dialysis
session

Campese VM TA. Hypertension in dialysis patients. 2004.
 All classes of antihypertensive can be used in
dialysis patients (Except diuretics).
 Compelling indications are similar
Treatment of Hypertension
 ARBs and ACE are the preferable first line of
antihypertensive drugs
 Prevent left ventricular hypertrophy
Cannella G etal.Am J Kidney Dis. 1997 Nov; 30(5):659-64.
Suzuki H et al. Am J Kidney Dis. 2008 Sep; 52(3):501-6.
Pharmacokinetic properties of ACE Inhibitors in ESRD
T1/2(h)
normal
T1/2(h)
ESRD
Initial
dose in
HD
Captopril
2-3
20-30
12.5 q24h
25-50 q24h
Yes
Enalapril
11
prolonged
2.5 q24h
or q48h
2.5-10 q24h
or q48h
Yes
Fosinopril
12
prolonged
10 q24h
10-20 q24h
Yes
Lisinopril
13
54
2.5 q24h
or q48h
2.5-10 q24h
or q48h
Yes
Ramipril
11
prolonged
2.5-5q24h
2.5-10 q24h
yes
Henrich W. Principles and Practice of Dialysis
Maintenance Removal
dose in HD during HD
Pharmacokinetic properties of ARB’s in ESRD
T1/2(h)
normal
T1/2(h)
ESRD
Initial dose
in HD
Maintenance
dose in HD
Removal
during HD
9
?
4 q24h
8-32 q24h
No
11-15
11-15
75-150 q24h
150-300 q24h
No
Losartan
2
4
50 q24h
50-100 q24h
No
Telmisartan
24
?
40 q24h
20-80 q24h
No
Valsartan
6
?
80 q24h
80-160 q24h
No
Candesartan
Irbesartan
Henrich W. Principles and Practice of Dialysis
Pharmacologic properties of β-blockers in chronic dialysis
patients
T1/2(h)
normal
T1/2(h)
ESRD
Initial dose
in HD
Maintenance
dose in HD
Removal
during HD
Acebutolol
3.5
3.5
200 q24h
200-300 q24h
yes
Atenolol
6-9
<120
25 q48h
25-50 q48h
Yes
Carvedilol
4-7
4-7
5 q24h
5 q24h
no
Metoprolol
3-4
3-4
50 b.i.d.
50-100 b.i.d.
high
Propranolol
2-4
2-4
40 b.i.d.
40-80 b.i.d.
yes
Henrich W. Principles and Practice of Dialysis
Hypertension in hemodialysis patients treated with
atenolol or lisinopril: a randomized controlled trial.
Agarwal R et al NDT 2014
 ESRD with LVH
 lisinopril (n = 100) or atenolol (n = 100) each
administered three times per week after dialysis.
 Results:
 Hospitalizations for heart failure were worse in the
lisinopril group (IRR 3.13, P = 0.021).
 All-cause hospitalizations were higher in the lisinopril
group [IRR 1.61 (95% CI 1.18-2.19, P = 0.002)].
Resistant Hypertension
• Blood pressure remaining above goal in spite
of concurrent use of 3 antihypertensive agents of
different classes.
Resistant HTN in ESRD
 Transdermal clonidine at weekly intervals.
 Minoxidil, a potent vasodilator,
 used with beta blockers
 Spironolactone in Hemodialysis Patients
 25-50 mg post dialysis
 Risk of hyperkalemia
 Improve EF and Improve BP control
 Large studies are done
Resistant Hypertension
 The use of non steroidal anti-inflammatory drugs
 Renovascular hypertension
 Increasing cysts in polysystic kidney disease
 Compliance
Resistant HTN in ESRD
 Renal sympathetic nerve ablation
 Hyperactivation of the sympathetic nervous system

J Clin Hypertens (Greenwich). 2012 Nov;14
 The Future?
 Device-Based Therapy for Resistant Hypertension


Baroreflex Activation Therapy
Renal Denervation Therapy
Baroreflex Activation Therapy (BAT)
Continuously Modulates the Autonomic Nervous
System
Carotid
Baroreceptor
Stimulation
Inhibit
sympathetic &
Enhance Parasymp
Heart
HR
Vessels
Kidney
Vasodilation Natriuresis
Renin
secretion
Anatomical Location of Renal
Sympathetic Nerves
 Arise from T10-L1
 Follow the renal artery to
the kidney
 Primarily lie within the
adventitia
The Journal of Clinical Hypertension. 14, pages 799–801,2012
Circulation. 2002;106:1974–1979
Intradialytic hypertension
 5-15%
 Mechanism







Extracellular volume overload
Increased cardiac output
Changes in sodium levels
Activation of the renin–angiotensin–aldosterone system
Overactivity of the sympathetic nervous system
Endothelial cell dysfunction.
Removal of anti HTN during dialysis
Intradialytic Hypertension
 The most important treatment is adequate sodium
and water removal and reducing sympathetic
hyperactivity.
 Changing to non-dialyzable antihypertensive
medications
 Altering the dialysis prescription.
Summary
 Sodium excess and extracellular volume expansion is
the major factor in the development of hypertension.
 Lifestyle modifications is critical.
 Control of volume status (Dietary salt and fluid
restriction).
 Correcting adequately volume expansion with dialysis.
 All classes of antihypertensive drugs can be used in
dialysis patients
Thank You