1. 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

2. Contents 1.Hypertension in dialyzed children 2.Hypotension during hemodialysis

3. 1.Hypertension in dialyzed children 2.Hypotension during hemodialysis

4. 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

5. Prevalence of hypertension in dialyzed children Mitsnefes et al. Am J Kidney Dis 2005, 45:309-315 Van De Voorde et al. Pediatr Nephrol 2007, 22:547-553 3,743 pts in NAPRTCS: start 1 yr 2 yr Uncontrolled hypertension56.9% 51% 48% Controlled hypertension 19.7% Normotensive23.4% Risk factors for uncontrolled hypertension at follow-up: Baseline hypertensive, receiving antihypertensive medication Age <12 (highest in 0-1 yo) High interdialytic weight gain High serum phosphorus Acquired kidney disease

6. 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

7. 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

8. 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

9. 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)

10. Nocturnal BP predicts cardiovascular death in adult hemodialysis patients Relative risk p Predialytic systolic BP0.990.94 Predialytic diastolic BP0.490.03 24h sytolic BP1.370.09 Nighttime systolic BP1.410.01 Amar et al. Kidney Int 2000, 57:2485-2491

11. Non-Dipping Predicts LV Hypertrophy and Cardiac Death in Hemodialysis Patients Liu et al Nephrol Dial Transplant 2003, 18: 563–569

12. 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

13. 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.

14. 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).

15. Short daily HDF 3*4h 5-6*3h Weekly Kt/V urea: 4.2 7.9 Serum phosphate: 1.87 1.28 Serum homocysteine: 21.6 13.4 Hemoglobin: 11.8 13.7 Epo dose: 83 59 Mean arterial pressure: 95 87 Interventricular septum: 10.9 6.8 Ejection fraction: 55 62 Fischbach et al. Nephrol Dial Transplant 2004, 19: 2360–2367

16. 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 )

17. Refractory Hypertension concurrent use of medication that raise BP renovascular hypertension polycystic kidney disease consider nephrectomy noncompliance to medical regimen

18. 1.Hypertension in dialyzed children 2.Hypotension during hemodialysis

19. Pathophysiology During hemodialysis (fluid removal): Plasma refilling Passive venoconstriction Increase in heart rate and contractility Increase in arterial tone Impaired compensatory responses hypotension

20. 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

21. 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)

22. Blood volume monitoring Hothi et al. Pediatr Nephrol 2008, 23: 813-820 Jain et al. Pediatr Nephrol 2001 16: 15-18 The control of blood volume (BVM) during hemodialysis was associated with less adverse events (hypotension).

23. Conclusion Hypertension in dialyzed children most common cause: fluid overload ! Hypotension during dialysis check for avoidable causes

24. Thank you for your attention