G. Simonetti and F. Schaefer

Pediatric Nephrology, Center for Pediatric and Adolescent Medicine,

University of Heidelberg, Germany

Management of High and

Low Blood Pressure

in Dialysis Children

Contents

1. Hypertension in dialyzed children

2. Hypotension during hemodialysis

1. Hypertension in dialyzed children

2. Hypotension during hemodialysis

Background

Arterial hypertension is an important risk factor for

cardiovascular diseases

Long term survival of childhood - onset ESRD patients

→ depends on cardio/cerebrovascular diseases

Oh et al. Circulation 2002;106:100-5

Prevalence of hypertension in dialyzed children

Mitsnefes et al. Am J Kidney Dis 2005, 45:309-315Van De Voorde et al. Pediatr Nephrol 2007, 22:547-553

3,743 pts in NAPRTCS:

start 1 yr 2 yr

Uncontrolled hypertension 56.9% 51% 48%

Controlled hypertension 19.7%

Normotensive 23.4%

Risk factors for uncontrolled hypertension at follow-up:Baseline hypertensive, receiving antihypertensive medication Age <12 (highest in 0-1 yo)High interdialytic weight gainHigh serum phosphorusAcquired kidney disease

Mechanisms of hypertension in CKD - 1

Salt and water retention• Plasma volume correlated with BP

– Strict enforcement of dry weight normalizes BP in most dialysis patients

– However, poor correlation of interdialytic weight gain and BP

Renin-Angiotensin-Aldosterone System• Normal levels despite hypervolemia• Insuppressible by saline infusion• Excessive local production by scarring renal tissues?

Sympathetic hyperactivation • Triggered by afferent signals from diseased kidneys • Persistent on dialysis, post-Tx; normalized by Nephrectomy• Stimulated by intrarenal Ang II; normalized by ACE inhibition

Endothelial Factors• Impaired endothelium derived vasodilation• Accumulation of circulating NOS inhibitor ADMA

Circulating Endothelin-1 elevated, correlates with BP

PTH/Calcium• PTH levels correlates with BP in 1° hyperparathyroidism• PTH/elevated cytosolic calcium enhances pressor responses• PTH suppresses eNOS expression

Intrauterine Programming• Barker/Brenner hypothesis: intrauterine malnutrition

causes oligonephronia and programs for hypertension

Mechanisms of hypertension in CKD - 2

ABPM in children undergoing Dialysis

Lingens et al. Pediatr Nephrol 1995, 9:167-172

• No correlations were found between ABPM and casual BP measurements, except for systolic day-time BP in PD patients

• BP assessed by ABPM was higher in PD than in HD patients. The physiological decline of BP at night was significant and more pronounced in PD than in HD patients

• Casual BP recordings are not representative of average BP in dialyzed pediatric patients

• ABPM is useful in the diagnosis and treatment of hypertension in dialyzed children

“Reverse epidemiology” of BP-mortality relationship in adult HD patients ?

Kalantar-Zadeh et al. Hypertension 2005, 45: 811-817

Low blood pressure before

dialysis seems to represent a risk

for cardiovascular events

But

→ Short follow-up of these studies

→ Patients with lower pressures

may represent a sicker

population (myocardial

dysfunction, poor nutrition)

Nocturnal BP predicts cardiovascular death in adult hemodialysis patients

Relative risk p

Predialytic systolic BP 0.99 0.94Predialytic diastolic BP 0.49 0.03

24h sytolic BP 1.37 0.09

Nighttime systolic BP 1.41 0.01

Amar et al. Kidney Int 2000, 57:2485-2491

Non-Dipping Predicts LV Hypertrophy and Cardiac Death in Hemodialysis Patients

Liu et al Nephrol Dial Transplant 2003, 18: 563–569

Treatment of hypertension in dialyzed children

• Control of volume status- discourage large interdialytic weight gains

- control salt intake

- control of ultrafiltration with blood volume monitoring (BVM)

• Prolonged and/or more frequent hemodialysis

• Adequate dialysis (Kt/V!)

- sodium profiling

• Antihypertensive medications

- only if elevated BP despite reaching dry weight

Improved HD Patient Survival by Strict Volume Control

Ozkahya et al. Nephrol Dial Transplant 2006, 21: 3506-3513

Adult patients with better

volume control (assessed by

the cardio-thoracic-index, CTI)

have a better survival

compared to patients with a

more pronounced

overhydration.

Improved blood pressure control with blood volume monitoring during hemodialysis

Patel et al. Clin J Am Soc Nephrol 2007; 2: 252–257

A better control of overhydration

was achieved with the use of

BVM. At the end of the study a

better blood pressure control was

observed (ABPM).

Short daily HDF 3*4h 5-6*3h

Weekly Kt/V urea: 4.2 7.9

Serum phosphate: 1.87 1.28Serum homocysteine: 21.6 13.4

Hemoglobin: 11.8 13.7Epo dose: 83 59

Mean arterial pressure: 95 87Interventricular septum: 10.9 6.8Ejection fraction: 55 62

Fischbach et al. Nephrol Dial Transplant 2004, 19: 2360–2367

Antihypertensive medications

• Only if blood pressure remains elevated despite the attainment of dry

weight

• Agent preferably with a once per day dosing schedule (long acting drugs)

• Greater benefits with

- ACE Inhibitors

- Angiotensin Receptor Blocker

• Calcium Channel Blockers and β-Blockers

→ probably not indicated in hemodialyzed children (vessels complicance ↓)

Refractory Hypertension

• concurrent use of medication that raise BP

• renovascular hypertension

• polycystic kidney disease

→ consider nephrectomy

• noncompliance to medical regimen

1. Hypertension in dialyzed children

2. Hypotension during hemodialysis

Pathophysiology

During hemodialysis (fluid removal):

• Plasma refilling

• Passive venoconstriction

• Increase in heart rate and contractility

• Increase in arterial tone

Impaired compensatory responses

→ hypotension

Factors contributing to arterial hypotension

• Factors causing arterial dilatation

- antihypertensive drugs

• Paradoxical decrease in sympathetic activity

• Conditions associated with reduced cardiac refilling

- left ventricular hypertrophy

- diastolic dysfunction

- structural heart defects

• Plasma refilling

- if UF rates exceed refilling rates, the intravascular volume

fall

Preventing intradialytic hypotension

- No antihypertensive drugs on dialysis days

- Avoiding food during dialysis

- Cooling dialysate

- Sodium profiling

- Discourage large interdialytic weight gains

- Control of fluid removal with BVM (Blood Volume Monitoring)

- (Midodrine)

- (Prophylactic caffeine administration)

Blood volume monitoring

Hothi et al. Pediatr Nephrol 2008, 23: 813-820Jain et al. Pediatr Nephrol 2001 16: 15-18

The control of blood volume (BVM)

during hemodialysis was associated with

less adverse events (hypotension).

Conclusion

Hypertension in dialyzed children

→ most common cause: fluid overload !

Hypotension during dialysis

→ check for avoidable causes

Thank you for your attention