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

32
16
8
4
Stroke Heart
16
8
4
2
2 1
<120 125 135 148 168 120 125 135 148 168
SYSTOLIC BLOOD PRESSURE mm Hg

Unadjusted survival by baseline predialysis systolic BP
Stidley et al. J Am Soc Nephrol 2006;17:513-520

 Low BP is a consequence of other disease:
 Major CVD
 Malnutrition-inflammation-atherosclerosis complex
 LVD



 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

 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

 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

 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

 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

 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

 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.

 Body weight:
 'obesity paradox‘
 Mainly explained by mal-or undernutrition.
 Low salt intake
 1000 to 1500 mg of sodium/day
 Exercise

 Tobacco use
 59% more CHF
 68% more PVD
 Mortality 37%

Foley et al. Kidney Int 2003; 63: 1462-7.

 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.

 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.

 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

 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
Maintenance dose in HD
Removal during HD
Captopril 2-3 20-30 12.5 q24h 25-50 q24h Yes
Enalapril 11 Yes
Fosinopril
Lisinopril
Ramipril
12
13
11 prolonged 2.5 q24h or q48h
2.5-10 q24h or q48h prolonged 10 q24h 10-20 q24h
54 2.5 q24h or q48h
2.5-10 q24h or q48h prolonged 2.5-5q24h 2.5-10 q24h
Yes
Yes yes
Henrich W. Principles and Practice of Dialysis

Pharmacokinetic properties of ARB’s in ESRD
Candesartan
Irbesartan
Losartan
Telmisartan
Valsartan
T1/2(h) normal
T1/2(h)
ESRD
Initial dose in HD
Maintenance dose in HD
9 ?
4 q24h 8-32 q24h
11-15 11-15 75-150 q24h 150-300 q24h
2
24
4
?
50 q24h
40 q24h
50-100 q24h
20-80 q24h
6 ?
80 q24h 80-160 q24h
Removal during HD
No
No
No
No
No
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
Atenolol
Carvedilol
Metoprolol
Propranolol
3.5
6-9
4-7
3-4
2-4
3.5
<120
4-7
3-4
2-4
200 q24h 200-300 q24h
25 q48h 25-50 q48h
5 q24h
50 b.i.d.
5 q24h
50-100 b.i.d.
40 b.i.d.
40-80 b.i.d.
yes
Yes no high 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)].

• Blood pressure remaining above goal in spite of concurrent use of 3 antihypertensive agents of different classes.

 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

 The use of non steroidal anti-inflammatory drugs
 Renovascular hypertension
 Increasing cysts in polysystic kidney disease
 Compliance

 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
Heart
HR
Carotid
Baroreceptor
Stimulation
Inhibit sympathetic &
Enhance Parasymp
Vessels Kidney
Vasodilation Natriuresis
Renin secretion

 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

 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

 The most important treatment is adequate sodium and water removal and reducing sympathetic hyperactivity.
 Changing to non-dialyzable antihypertensive medications
 Altering the dialysis prescription.

 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