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Intradialytic Hypertension (IDH) HTA intradialytique Malik Touam 23-24 avril 2012 Malik Touam AURA & Hôpital Necker Paris

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Intradialytic Hypertension (IDH)

HTA intradialytique

Malik Touam

23-24 avril 2012

Malik Touam

AURA & Hôpital Necker Paris

HID

• Definition• Prevalence• Clinical Characteristics• Prognostic significance

Intradialytic Hypertension

• Prognostic significance• Pathophysiologic Mechanisms• Treatment

Definition - Intradialytic hypertension

•BP measurement during dialysis session- Peridialytic hypertension

•BP measurement before & immediately after dialysis session- Interdialytic hypertension

•Home BP or ambulatory BP

Agarwal & Sinha Am J Kidney Dis 2009

KDOKI Guidelines, Am J Kidney Dis 2005

Agarwal & Sinha Am J Kidney Dis 2009

Home Blood Pressures Are of Greater Prognostic Valu e than Hemodialysis Unit Recordings

Prospective cohort study in 150pts on chronic HD dialyzing atfour university-affiliated units.

BP evaluation:• HBPM for 1 wk,• interdialytic ABPM;• interdialytic ABPM;• “routine” and standardizedmethods in the dialysis unit for 2weeks.

Median follow-up: 24 months.CV death occurred in 26 (17%)pts and death in 46 (31%) pts.

Alborzi P et al. Clin J Am Soc Nephrol 2007

Definition

Chazot , Nephron Clin Pract 2010

NB: low, normal or high predialysis BP

Prevalence of IDHCRIT-Line Intradialytic Monitoring Benefit (CLIMB) study

N = 443 prevalent HD150

200

250N

PAS PAS PAS<10 mm Hg =10 mm Hg >10 mm Hg

Inrig et al, Kidney Int, 2007

53%

34%

13%0

50

100

c c c

94% postdialysis HTN

Distribution of change in SBP during HD in incident HD patients cohorte DMMS Wave 2 Study (USRDS)

• N = 1748 incident HD • HID =12% 93% postdialysis HTN

Inrig et al, Am J Kidney Dis 2009

Clinical Characteristics

DMMS Wave 2 Study- SBP >10 mm Hg (N = 744)- Unchanged SBP (N = 791)- SBP >10 mm Hg (N = 213)

• Older patients• Lower BMI, dry weight and interdialytic weight gain• Lower serum creatinine and serum albumin levels• More predialysis HTN • More antihypertensive medications

Inrig et al Am J Kidney Dis 2009

Cardiovascular Characteristics

60 patients30 IDH (MAP>15 mm Hg) vs 30 control

Chou et al , Kidney Int, 2006

Prognostic

N = 5433

Zager et al Kidney Int 1998

Prognostic N = 40933

Kalantar Zadeh et al, Hypertension 2005

Prognostic

Inrig et al, Am J Kidney Dis 2009

Prognostic Kaplan-Meier survival curves of time to death over 2 years in a national cohort of incident hemodialysis (HD)

patients stratified by changes in systolic blood pressure (SBP) during HD

Inrig et al Am J Kidney Dis 2009

Pathophysiologic Mechanisms

Inrig, Am J Kidney Dis 2009

Volume Overload

6 HD patients

Gunal, J Nephrol 2002

Volume Overload

9 HD patients with postdialysis HTN BPS: 172 204 mm HgPedal edema: only 3 patientsReduction of dry weight (mean -6,7 kg)Reduction of dry weight (mean -6,7 kg)

Reduction of antihypertensive medicationsNormalization of BP

Cirit et al, Nephrol Dial Transplant 1995

The effect of dry-weight reduction on interdialytic ambulatory systolic (A) and diastolic BP (B) in hypertensive hemodialysis patients

DRIP studyPrevalent HD

Agarwal et al, Hypertension 2009

Prevalent HD

Relationship of change in systolic ambulatory BP with ultrafiltration vs the change in postdialysis weight

Agarwal et al, Hypertension 2009

Intradialytic hypertension is a marker of volume excess

• DRIP study: post hoc analysis– 100 IDH vs 50 control

• 30 dialysis sessions• Ambulatory and BP dialysis unit measurements• Ambulatory and BP dialysis unit measurements• Reduction of dry body weight (-1 Kg, 4-8 weeks)

– Reduction of intradialytic BP (- 3%)– Reduction of interdialytic BP

• SBP - 6,6 mm Hg• DBP - 3,3 mm Hg

Agarwal et al Nephrol Dial Transplant 2010

Dialysis Specific factorsSodium

Song et al J Am Soc Nephrol 2005

Sodium

Blood pressure responses to dialysate sodium individualization according to baseline blood pressure. Phase 1, standard Na (140 mEq/L); phase 2, individualized Na.

De Paula et al. Kidney Int 2004

Sodium • 11 patients• Na 138, 140, 147 mmol/l• 6 semaines

Song et al Am J Kidney Dis 2002

Regression analysis indicates that positive sodium load occurred with TACNa more than 137.8 mmol/L.

• Hypokaliemia: direct vasoconstrictor effect• Acute increase Ca++: increases myocardial contractility and cardiac output

Potassium – Calcium

Chou et al Kidney int 2006

Sympathic Overactivity

11 HD4 anephric HD8 normal renal function

Catecholamines & Renin-Angiotensin-Aldosteron Syste m

Chou et al Kidney int 2006

Endothelial Cell Dysfunction

Raj et al Kidney Int 2002

Serum ( ) and dialysate ( ) concentrations of nitri te + nitrite (NT) during hemodialysis ( N = 27, mean SD).Dialysate NT increased significantly from base line at mid-dialysis (*P < 0.001) and then decreased. Serum NT concentration decreased significantly from pre-dialysis values at mid and post-dialysis (*P < 0.001).

Hemodynamic changes during hemodialysis: Role of ni tric oxide and endothelin

Raj et al Kidney Int 2002

Endothelial Cell Dysfunction

Chou, et al Kidney Int 2006

Endothelial Cell Dysfunction

Figure 2. | Endothelial progenitor cells (EPCs) among subjects without and with intradialytic hypertension. EPCs are reported as a median percentage of mononuclear cells, 25th to 75th percentile interquartile range, and 5th to 95th percentage error bars.

Inrig et al, CJASN 2011

Erythropoietin-Stimulating Agents

Krapf et al CJASN 2009, Hand et al Kidney Int 1995

Percent change in forearm vascular resistance in response to brachial artery norepinephrine infusion in hemodialysis patients before and at 6 and 12 wk after the start of sustained Epo treatment. Open circles reflect baseline values before treatment, closed triangles represent values at 6 wk ofEpo treatment, and squares reflect values after 12 wk of Epo treatment.

Antihypertensive medications

Inrig, Semin Dialysis 2010

Antihypertensive medications

Antihypertensive medications

Inrig J, Semin Dialysis 2010 [[ Heerspink HJ Lancet 2009]]

Reduction in systolic ambulatory BP with ultrafiltr ation vs the control group

Agarwal, R. et al. Hypertension 2009

Potential strategies for the treatment of intradialytic hypertension

Locatelli et al Nat. Rev. Nephrol. 2009

Treatment of IDH

Chazot, Nephron Clin Pract 2010

Conclusion

• IDH present in 5-15% of HD patients• More common in patients who are older , have lower dry

weights and are prescribed more antihypertensive drugs• IDH is associated with a increased risk of hospitalization

or death at 6 months• Important role of endothelial cell dysfuntion• Important role of endothelial cell dysfuntion• Treatment should be individualized

– Decreasing dry weight +++ (sodium balance neutral or negative)– Altering the dialysis prescription– Select antihypertensive medications according to the elimination

profile – Suspend ESA or switch from intravenous to subcutaneous ESA

The lingering dilemma of arterial pressure in CKD:what do we know, where do we go?

1. What is the optimal level of target blood pressure (BP)among patients with chronic kidney disease (CKD)? Does this target depend on the severity of proteinuria? Should elderly

patients with CKD have the same target levels of BP as younger patients?

2. What is the optimal level of target BP in patients with end-stage renal disease (ESRD) on dialysis? How should thesetargets be achieved: diet, drugs, or dry weight? What is the impact of lowering BP on residual renal function, cardiac function, and

overall outcomes among hemodialysis patients?

3. What is the role of excess volume in the genesis ofhypertension among patients with CKD? Does the pathophysiology vary as a function of clinical and

demographic factors such as age, sex, race, and proteinuria?

4. What markers indicate excess volume among dialysis patients?

5. What is the optimal BP measurement technique and timing among those with CKD, including those on dialysis? What shouldbe the reference standard for the diagnosis and management ofbe the reference standard for the diagnosis and management of

these patients? Clinic or dialysis unit BP, home BP, or ambulatory BP?

6. What are the treatable causes of resistant hypertension among patients with CKD? What is the magnitude and timecourse of benefit that can be expected with treatment?

7. What is the role of non-volume factors in sustaining hypertension in CKD? Sympathetic activation, therenin–angiotensin system, endothelin, asymmetrical dimethylarginine (ADMA), renalase, etc.

8. What are the risks and benefits of mineralocorticoidreceptor antagonists in the treatment of hypertension in patients with CKD?

9. What is the independent prognostic significance of BPpatterns among patients with CKD?

10. How does the evaluation of arterial stiffness add to themanagement of hypertension among patients with CKD?

EUropean REnal and CArdiovascular Medicine (EURECA-m) working group of the European Renal Association–European Dialysis and Transplant Association (ERA–EDTA)

Kidney Int Suppl 1,17-20, 2011