lecture intradialytic hypertension - schedschd.ws/hosted_files/psnannual2015/53/lecture...

Intradialytic Hypertension

2015 Annual PSN Convention

EDSA Shangrila, April 16, 2015

Objectives:

To discuss the:

Epidemiology of intradialytic hypertension

Pathophysiology

Management

Intradialytic Hypertension: Definitions

An increase in mean arterial blood pressure (MAP) ≥

15 mmHg during or immediately after hemodialysis

An increase in systolic BP (SBP) >10 mmHg from pre

to postdialysis

sustained increase of BP during the dialysis session with BP values

during and at the end of the dialysis session exceeding BP values at

dialysis onset

Hypertension during the second or third hour of

hemodialysis after significant ultrafiltration has taken

place

An increase in BP that is resistant to ultrafiltration

Inrig JK. Intradialytic hypertension: a less-recognized cardiovascular complication of hemodialysis. Am

J Kidney Dis. 2010 March ; 55(3): 580–589 Chazot C and Jean G. Intradialytic hypertension: It is time to act. Nephron Clin Pract 2010;115:c182–c188


A ≥10 mmHg increase in systolic blood

pressure from pre to post HD

Dialysis Morbidity and Mortality Wave 2 Study

Crit-Line Intradialytic Monitoring Benefit

Study

Van Buren P, et al. Interdialytic ambulatory blood pressure in patients with intradialytic hypertension. Curr

Opin Nephrol Hypertens. 2012;21:15–23.

Prevalence of Intradialytic hypertension

443 hemodialysis patients

From the Crit-Line Intradialytic

Monitoring Benefit Study

Inrig JK, et al. Association of intradialytic blood pressure changes with hospitalization and mortality rates in prevalent ESRD

patients. Kidney International 2007;15:454-461. downloaded at http://www.nature.com/ki/journal/v71/n5/pdf/5002077a.pdf

I

Inrig J, et al. Association of blood pressure increases during hemodialysis with 2-year mortality in incident hemodialysis patients: a

secondary analysis of the dialysis morbidity and mortality wave 2 study. Am J Kidney Dis. 2009; 54(5): 881–890. Downloaded at

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767411/

Prevalence of Intradialytic Hypertension 1748 Incident HD patients, (Dialysis Morbidity and Mortality Wave 2 Study)

Intradialytic Hypotension Intradialytic Hypertension

12% 42.6%

Systolic BP change (ΔSBP) associated with hemodialysis

ΔSBP ≤

-10mmHg

n=230 (52.5%)

(Intradialytic

hypotension)

ΔSBP -10 to 10 mmHg

n = 150 (34.4%)

(Stable BP)

ΔSBP ≥ 10 mmHg

n=58

(13.2%)

(Intradialytic

hypertension)

P-value

Age (yrs) 57.36 (±14.97) 60.34 (±16.0) 63.64 (± 16.54) 0.013

Predialysis SBP 155.46

(± 18.40)

144.51 (± 22.45) 139.28 (± 21.62) <0.0001

Predialysis DBP 82.49 (± 11.96) 77.19 (± 13.52) 73.76 (± 12.17) <0.0001

Postdialysis SBP 130.52

(± 17.26)

142.43 (± 21.88) 157.92 (± 20.53) <0.0001

Postdialysis DBP 71.30 (± 11.00) 75.48 (± 12.9) 79.33 (± 12.32) <0.0001



Comparison of age and predialysis BP: Crit-Line

Intradialytic Monitoring Benefit Study

Systolic BP change (ΔSBP) associated with hemodialysis

ΔSBP ≤

-10mmHg

n=744 (42.6%)

(Intradialytic

hypotension)

ΔSBP -10 to 10 mmHg

n = 791 (45.2%)

(Stable BP)

ΔSBP ≥ 10 mmHg

n=213

(12.2%)

(Intradialytic

hypertension)

P-value

Age (yrs) 61.0 (±14.8) 61.8 (±16.0) 62.0 (± 15.5) 0.5

Predialysis SBP 159.1

(± 19.3)

144.9 (± 20.3) 143.2 (± 20.6) <0.001

Predialysis DBP 81.5 (± 11.7) 75.9 (± 12.3) 76.3 (± 12.6) <0.001

Dry weight

(kg/m2)

75 (± 20) 70.8 (± 19.1) 68.3 (± 17.8) <0.001

IDWG 3.33 (± 1.73) 3.05 (± 1.81) 2.74 (± 2.13) <0.001

Comparison of age and predialysis BP: Dialysis

Morbidity and Mortality Wave 2 study

Inrig J, et al. Association of blood pressure increases during hemodialysis with 2-year mortality in incident

hemodialysis patients: a secondary analysis of the dialysis morbidity and mortality wave 2 study. Am J Kidney

Dis. 2009; 54(5): 881–890. Downloaded at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767411/

Combined outcome of 6-month mortality and

non-access-related hospitalization



Adjusted Odds Ratio

(95% CI)

SBP fell with HD (ΔSBP ≤ -10mm Hg) 1.00 (reference)

SBP unchanged with HD (ΔSBP 10 to 10mm Hg) 2.08 (1.19–3.61)

SBP rose with HD (ΔSBP ≥10mm Hg) 2.61 (1.29–5.27)

ΔSBP (per 1mm Hg increase) 1.02 (1.01–1.04)

Crit-Line Intradialytic Monitoring Benefit Study

Non access related hospitalization and

ΔSBP per 10 mmHg increment



Crit-Line Intradialytic Monitoring Benefit Study

Intradialytic and hypertension and 2-yr mortality

rate: Dialysis Morbidity/Mortality Wave 2 study

Inrig J, et al. Association of blood pressure increases during hemodialysis with 2-year mortality in incident

hemodialysis patients: a secondary analysis of the dialysis morbidity and mortality wave 2 study. Am J Kidney

Dis. 2009; 54(5): 881–890. Downloaded at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767411/

Hazards ratio for all cause mortality

Park J, et al. A comparative effectiveness research study of the change in blood pressure during

hemodialysis treatment and survival. Kidney International (2013) 84, 795–802

• Retrospective cohort study of 113,255 hemodialysis patients

• 5-year period

• Evaluate an association between change in BP during hemodialysis and mortality

Potential Pathophysiologic Mechanisms

of Intradialytic Hypertension

Extracellular Volume overload

Sympathetic over-activity

Activation of the renin-angiotensin aldosterone

system

Endothelial cell dysfunction

Removal of Antihypertensives During

Hemodialysis

Inrig, J. Intradialytic Hypertension:Intradialytic Hypertension: A less-recognized cardiovascular complication of hemodialysis. Am j of Kidney

disease. 2010;55:580-589

Potential Pathophysiologic Mechanisms of


Dialysis-specific factors

net sodium gain

high ionized calcium

Medications

Erythropoietin stimulating agents

Removal of antihypertensive medications

Inrig, J. Intradialytic Hypertension:Intradialytic Hypertension: A less-recognized cardiovascular complication of hemodialysis. Am j of Kidney

disease. 2010;55:580-589

Characteristics of pts prone to intradialytic hypertension

Chou KP, et al. Physiological changes during hemodialysis in patients with intradialysis hypertension.

Kidney International 2006;69,1833–1838

Patient characteristics Intradialytic Controls P-value

Hypertension

Age (years) 53.2 ± 3.9 54.3 ± 4.2 NS

Duration of maintenance 49.9 ± 7.4 53.1 ± 9.1 NS dialysis (months)

Body weight (kg) 52.2 ± 1.6 53.9 ± 2.0 NS

Ultrafiltration volume (l) 2.1 ± 0.3 2.3 ± 0.3 NS

Serum albumin (g/dl) 4.2 ± 0.1 4.2 ± 0.1 NS

i-PTH (pg/ml) 189.7 ± 56.2 343.7 ± 105.7 NS

Baseline Hct (%) 28.5 ± 1.1 28.8 ± 0.6 NS

Baseline mean 105 ± 3 95 ± 3 <0.05

mean arterial pressure (mmHg)

Baseline pulse rate (min1) 73 ± 2 72 ± 2 NS

Physiologic changes during dialysis



Sympathetic and Renin activation markers



Laboratory data Intradialytic Controls P-value

after hemodialysis Hypertension

Before hemodialysis

Plasma epinephrine (pg/ml) 97.1 ± 13.5 99.0 ± 8.5 NS

Plasma norepinephrine (pg/ml) 225 ± 43 253 ± 47 NS

Plasma renin concentration (pg/ml) 10.8 ± 3.4 15..1 ± 3.1 NS

After hemodialysis

Plasma epinephrine (pg/ml) 87.6 ± 9.8 100.4 ± 6.8 NS

Plasma norepinephrine (pg/ml) 204 ± 27 363 ± 62* <0.05

Plasma renin concentration (pg/ml) 10.6 ± 2.8 24.9 ± 7.3* <0.05

* P<0.05 when compared with values before hemodialysis.

Nitric oxide and endothelin levels

Laboratory data Intradialytic Controls P-value

after hemodialysis Hypertension

Before hemodialysis

NO (mM) 41.2 ± 6.1 32.9 ± 5 NS

ET-1 (pg/ml) 345.6 ± 34.5 287.4 ± 29.3 NS

NO/ET-1 0.869 ± 0.502 0.129 ± 0.013 NS

After hemodialysis

NO (mM) 7.2 ± 0.9** 7.9 ± 0.9** NS

ET-1 (pg/ml) 510.9 ± 43.3** 276.7 ± 30.1 <0.05

NO/ET-1 0.018 ± 0.003** 0.034 ± 0.005** <0.05



Endothelial cell dysfunction in intradialytic

hypertension

Van Buren P, et al. Interdialytic ambulatory blood pressure in patients with intradialytic hypertension. Curr

Opin Nephrol Hypertens. 2012;21:15–23.

Vessel lumen Vessel lumen

Endothelial cell Endothelial cell

Vascular smooth muscle Vascular smooth muscle

Vessel wall Vessel wall

Increased

serum

sodium

concentrati

on

Circulating

endothelial

progenitor

cell

NO receptor

Vasodilation

ETA receptor

vasoconstrition

Nitric oxide

eNOS Impaired flow

Mediated vasodilation

Intradialytic

hypertension

NO receptor

vasodilation

eNOS

Nitric oxide ET-1

ETA receptor

vasoconstrition

ET-1

Circulating

endothelial

progenitor

cell

?

Increase in BP after initiation of

erythropoietin therapy

Hemodialysis Predialysis

Sys

toli

c B

loo

d p

res

su

re, m

mH

g

55

50

45

40

35

30

25

Noshad H. Blood pressure increase after erythropoietin injection in hemodialysis and predialysis patients. IJKD

2013;7:220-225. Downloaded at http://www.ijkd.org/index.php/ijkd/article/view/873/539

EPO and increase in BP

Miyashita K, et al. Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients.

Hypertens Res 2004; 27: 79–84. Downloaded at https://www.jstage.jst.go.jp/article/hypres/27/2/27_2_79/_pdf

EPO and endothelin release

Miyashita K, et al. Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients.

Hypertens Res 2004; 27: 79–84. Downloaded at https://www.jstage.jst.go.jp/article/hypres/27/2/27_2_79/_pdf

Intradialytic Hypertension: Management

Volume management

Inhibition of sympathetic nervous system

Inhibition of renin-angiotensin-aldosterone system

Pharmacologic inhibition of endothelin

Anti-hypertensive regimen

ESAs

Adjustment of dialysis prescription

Effect of ultrafiltration on intradialytic

hypertension: DRIP study

Agarwal R and Light R. Intradialytic hypertension is a marker of volume excess. Nephrol Dial Transplant

2010;25:3355–3361

Effect of ultrafiltration on BP reduction

Agarwal R, et al. Dry-Weight Reduction in Hypertensive Hemodialysis Patients (DRIP): A randomized

controlled trial. Hypertension. 2009;53:500-507

Weeks

Kayikcioglu M. The benefit of salt restriction in the treatment of ESRD by hemodialysis.

Nephrol Dial Transplant. 2009;24:956-962

Role of salt in Intradialytic Hypertension

• Center A (n=190): salt restriction strategy

strict salt restriction: 5grams NaCl/day

and ultrafiltration

• Center B (n= 204): anti-hypertensive

based strategy

Centre A

(salt

restricted)

(n=190)

Centre B

(Antihypertensive

based)

(n=204)

P-value

Use of antihypertensive medication 13 (17%) 86 (42%) 0.001

Interdialytic weight gain 2.29 ± 0.83 3.31 ± 1.12 0.0001

Systolic BP (mmHg) 126 ± 15 126 ± 21 ns

Diastolic BP (mmHg) 75 ± 12 76 ± 11 ns

Systolic BP ≥ 140 (%) 18 37 0.001

Diastolic BP ≥ 90 %%) 12 8 ns



BP and weight gain of patients treated

LV measurements and indices Centre-A Centre-B P-value

(n = 190) (n = 204)

LV diastolic index (cm/m2) 2.61 ± 0.33 2.97 ± 0.64 0.000

LV end-systolic index (cm/m2) 1.60 ± 0.29 1.96 ± 0.47 0.0001

LV ejection fraction (%) 68 ± 10 63 ± 09 0.0001

Interventricular septal index(cm/m2) 0.79 ± 0.13 0.83 ± 0.14 0.018

LV fractional shortening (%) 39 ± 8 35 ± 6 0.0001

LV mass indexed to height (g/m) 59 ± 16 74 ± 27 0.0001

LV hypertrophy (%) 124 (74%) 171 (88%) 0.001

Echocardiographic data



Hypertension and fluid overload

Wabel P, et al. Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload.

Nephrol Dial Transplant 2008;23:2965-2971

BP

sys (

mm

Hg

)

200

180

160

140

120

100

80

-2 -1 0 1 2 3 4 5 6 7 8

Under

hydration Mild Normo-

hydration Gross

Overhydration

I

N

III IV

I-II

DX

HD patient

reference range

Healthy reference range

150 mmHg

100 mmHg

140 mmHg

10th percentile

10th percentile

Hypo-

tension

Hyper-

tension

90th percentile Δhydration status (L)

27%

19%

15% 13%

10%

Kidney Disease Improving Global Outcome (KDIGO)

2010 definition of hypertension in dialysis

pre-HD ≥ 140/90 mmHg

post-HD BP ≥130/80mmHg

Expert opinion!

Levin NA, et al. Blood pressure in chronic kidney dise ase stage 5D—report from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney International (2010) 77, 273–284

http://www.kidney.org/professionals/kdoqi/guidelines_cvd

…..that there was uncertainty about how to measure

BP in hemodialysis patients, a poor understanding

of the association between BP and risk of adverse

outcomes, and a complex interplay of factors

influencing both systolic and diastolic pressure

As a result, the KDIGO executive decided that it was premature to make recommendations regarding BP management in CKD Stage 5D patients

Consensus report on BP management in CKD 5

HR of antihypertensive therapy on cardiovascular events

Agarwal R , Sinha A D Cardiovascular protection with antihypertensive drugs in

dialysis patients: Review and Metaanalysis. Hypertension 2009;53:860-866

Risk ratios of antihypertensive therapy on CV events

Agarwal R , Sinha A D Cardiovascular protection with antihypertensive drugs in

dialysis patients: Review and Metaanalysis. Hypertension 2009;53:860-866

Copyright © American Heart Association

Antihypertensive treatment in Dialysis: ACEI/ARB

on cardiovascular events

Heerspink HJL, et al. Effect of lowering blood pressure on CVD events and mortality in patients on dialysis: a

systematic review and meta-analysis of RCTs. Lancet 2009

Antihypertensive drugs in CKD5D and mortality

Antihypertensive drug Adjusted hazards ratio

(95% CI)

p-value

Ca Channel blockers 1.0 (0.94, 1.07) 0.9

ACEI 1.05 (0.96, 1.17) 0.3

Beta blockers 0.84 (0.75, 0.93) 0.001

Alpha blockers 0.93 (0.80, 1.09) 0.4

Centrally active agents 4.0 (0.97, 1.17) 0.2

Vasodilators 0.99 (0.86, 1.14) 0.9

Foley RN, et al. Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves 3 and 4 Study. Kidney International 2002;62:1784–1790

11,142 hemodialysis patients from the United States Renal Data System (USRDS)

Agarwal R, et al. Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized

controlled trial. Nephrol Dial Transplant 2014; 29: 672–681

Effect of Atenolol vs Lisinopril on left ventricular

mass index

200 hemodialysis patients randomized to Lisinopril or Atenolol

Atenolol

Lisinopril

No. of antihypertensives needed: Lisinopril

vs Atenolol

Agarwal R, et al. Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized

controlled trial. Nephrol Dial Transplant 2014; 29: 672–681

Atenolol

Lisinopril

KDOQI Clinical Practice Guidelines:

Management of Blood Pressure in HD Patients

Blood pressure goals should be: (C)

Predialysis: <140/90 mm Hg

Postdialysis: <130/80mmHg

K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients. American Journal of

Kidney Diseases 2005;45:

HR for all-cause mortality associated with

technique of BP monitoring

BP technique Systolic BP p-value Diastolic BP p-value

Pre-HD 1.06 0.43 1.04 0.54

Post HD 1.17 0.49 1.06 0.41

Home BP 1.18 .014 1.13 0.042

Ambulatory 1.2 0.002 1.15 0.009

Agarwal R. Location not quantity of BP measurements predicts mortality in hemodialysis patients.

Am J Nephrol 2008;28:210-217

Interdialytic Ambulatory BP monitoring

Agarwal R. Management of hypertension in hemodialysis patients.

Hypertension International 2006;10:241-248

Intradialytic hypertension and the

association with 44-hr ambulatory BP

Van Buren P, et al. Intradialytic hypertension and the association with interdialytic ambulatory blood

pressure. Clin J Am Soc Nephrol 2011;6:1684–1691

Nonlinear relationship of systolic BP obtained outside the

dialysis unit and subsequent mortality over 6 years or

less.

Agarwal R. BP and mortality among hemodialysis patients

Hypertension 2010;55:762-768

Management of hypertension with drugs in dialysis

patients:

Antihypertensive drugs should be given

preferentially at night because it may reduce

the nocturnal surge of blood pressure and

minimize intradialytic hypotension, which may

occur when drugs are taken the morning

before a dialysis session. (C)



Removal of antihypertensive drugs in HD

Drugs % removal Drugs % removal

ACE inhibitors CCBs

Benazepril Yes Amlodipine ?

Enalapril 35 Nifedipine Low

Lisinopril 50 Diltiazem ?

Ramipril Yes Nicardipine ?

ARBs Felodipine ?

Losartan None Verapamil Low

Candesartan None β-Blockers

Telmisartan None Atenolol 75

Valsartan None Carvedilol None

Irbesatan None Metoproplol High

Others

clonidine 5 methyldopa 60



Removal of Antihypertensive Drugs with

Dialysis

Angiotension receptor blockers are not removed

during hemodialysis

Most beta blockers are removed except for Carvedilol

and Labetalol

Calcium channel blockers are also removed during

hemodialysis with the exception of Amlodipine, low

percentage removal for Nifedipine and Verapamil

Inrig, J. Intradialytic Hypertension. Am j of Kidney disease. 2010 March 55 (3), 580-589

Removal of Antihypertensive Drugs with

Dialysis

A small percentage of angiotensin converting

enzymes inhibitors are removed by hemodialysis

Clonidine has 5% removal during hemodialysis

Inrig, J. Intradialytic Hypertension. Am j of Kidney disease. 2010 March 55 (3), 580-589

CPG 2010: Hypertension in dialysis

patients (UK Renal Association)

We suggest that home or ambulatory blood

pressure recordings should be performed if pre-

and post- HD or clinic blood pressures are

consistently elevated or there is concern over

possible hypotension. (2C)

We suggest that dialysis patients should be on a

restricted sodium (<5g/day) diet. (2C)

We suggest that hypertension on dialysis should be

managed by ultrafiltration in the first instance. (2D)

Adjusting Dialysate Sodium

Santos SFF and Peixoto A. Revisiting the Dialysate Sodium Prescription as a Tool for Better Blood Pressure

and Interdialytic Weight Gain Management in Hemodialysis Patients. Clin J Am Soc Nephrol 2008;3: 522–530.

Standard Na+ Individualized Na

(140 meqs/L)

Dialysate - source of sodium!

72 kg man, total body water is 43L

If predialysis plasma Na+ is 135meq/L and the

dialysate bath contains 145 meqs/L, then he

receives 430meq Na+ (10 meq/L x 43 ml)

Agarwal R. Management of hypertension in hemodialysis patients. Hemodialysis International

2006;10:241-248

Implications of prescribing a high dialysate

sodium

Santos SFF and Peixoto A. Revisiting the Dialysate Sodium Prescription as a Tool for Better Blood Pressure

and Interdialytic Weight Gain Management in Hemodialysis Patients. Clin J Am Soc Nephrol 2008;3: 522–530.

Hypernatric Dialysate

Volume overload

Sodium removal

↑ Thirst

↑ Serum sodium

Hypertension Left ventricular hypertrophy

Congestive heart failure

Stroke

Death



Management of hypertension by adjustment of

dry weight

Education and regular counseling by dietitians

Low sodium intake (2–3 g/day sodium intake)

Increased ultrafiltration

Longer dialysis

More than 3 dialysis treatments per week



Summary: Intradialytic Hypertension

Intradialytic hypertension defined as > 10 mmHg

rise from preHD BP associated with increased

risk of hospitalization and mortality

Endothelial cell dysfunction and elevated

endothelin levels are emerging as an important

causes

Management:

Volume control through UF and salt restriction

Antihypertensive medicines

Consider home or ambulatory blood pressure

recordings if pre- and post- HD or are consistently

elevated

THANK YOU

lecture intradialytic hypertension - schedschd.ws/hosted_files/psnannual2015/53/lecture...

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