The Management of Hypertension In Hemodialysis Patients

Dr. Abdulkareem AlsuwaidaAssociate Professor King Saud University

Hemodialysis Symposium08-09 February 2014

Al Madinah AlMunawwarah

Iseki et al. Ther Apher Dial 2007;11:183-188

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Stidley et al. J Am Soc Nephrol 2006;17:513-520

Unadjusted survival by baseline predialysis systolic BP

“Reverse-epidemiology”Low BP is a consequence of other disease:

Major CVDMalnutrition-inflammation-atherosclerosis

complexLVD

Mechanism of HTNSodium and volume overload.Sympathetic nervous system activityInappropriate 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 HTNHypervolemia is the major factorPositive Sodium balance

Increases intake and decreased excretion Achieving DW will control 60% of cases of

HTNAssessment of DW

Am J Kidney Dis. 1996 Aug; 28(2):257-61

Mechanism of HTNRenin inappropriately high for ? etiology.

Increase vascular resistanceIncreased 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 AfterHome BPABPM

When and How to measure the BP in dialysis patients?Predialysis SBP overestimated mean SBP by

an average of 10 mm HgPostdialysis SBP underestimated mean SBP

by an average of 7 mm HgBP reasings over a period of 1 to 2 weeks

rather than isolated readings should be used

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 evidencePre-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 CHF68% more PVDMortality 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 weightFrequent dialysis & Longer dialysis time

Agarwal R, et al. Hypertension. 2009 Mar; 53(3):500-7.

Dry WeightCriteria 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 drugs160/95 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 drugsPrevent 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 ESRDT1/2(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 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

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

Candesartan 9 ? 4 q24h 8-32 q24h No

Irbesartan 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

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 LVHlisinopril (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.

Resistant Hypertension

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 hyperkalemiaImprove EF and Improve BP control Large studies are done

Resistant HypertensionThe use of non steroidal anti-inflammatory

drugsRenovascular hypertensionIncreasing cysts in polysystic kidney diseaseCompliance

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

HR Vasodilation Natriuresis Renin secretion

Anatomical Location of Renal Sympathetic Nerves

Arise from T10-L1Follow the renal

artery to the kidneyPrimarily lie within

the adventitia

The Journal of Clinical Hypertension. 14, pages 799–801,2012Circulation. 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 YouThank You