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  • Intradialytic Hypertension (IDH)

    HTA intradialytique

    Malik Touam

    23-24 avril 2012

    Malik Touam

    AURA & Hpital 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 Value 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 PAS10 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 System

    Chou et al Kidney int 2006

  • Endothelial Cell Dysfunction

    Raj et al Kidney Int 2002

  • Serum ( ) and dialysate ( ) concentrations of nitrite + 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 nitric 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 ultrafiltration 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, thereninangiotensin 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 AssociationEuropean Dialysis and Transplant Association (ERAEDTA)

    Kidney Int Suppl 1,17-20, 2011