Blood Pressure and Volume Management in Dialysis Patient Sawinee Kongpetch Nephrologist Kidney Excellence Center, KKU
Outlines Definition of Hypertension in Dialysis Patients How to Measure Blood Pressure in Dialysis Patients Blood Pressure and Volume Management in Dialysis Patient Intradialytic Hypertension Intradialytic Hypotension
Prevalence of Hypertension in Chronic HD Nephrol Dial Transplant (2017) 32: 620–640
Definition of Hypertension in Dialysis Patients
Diagnosis of Hypertension in Dialysis Patients * Hypertension in dialysis patients should be based on home BP or ABPM evaluation Home BP in HD: ABPM in HD: For HD patients: when neither average BP ≥ 130/80 mmHg ABPM nor HBPM are available, average BP ≥ 135/85 mmHg over 6 non-dialysis days, over 24-hour monitoring office BP ≥ 140/90 mmHg during mid-week non-dialysis day during a two-week period, and, if possible, extended to 44 taken in a mid-week non-dialysis measure in quiet room, in seated day, with the standard technique position, back and arms supported, hours after 5 minutes of rest and 2 measurements taken 1-2 minutes apart Home BP in PD: ABPM in PD: For PD patients: average BP ≥ 135/85 mmHg average BP ≥ 130/80 mmHg office BP ≥ 140/90 mmHg over 7 consecutive days with the above over 24-hour monitoring obtained with the standard technique described conditions as described above Braz. J. Nephrol. (J. Bras. Nefrol.) 2019;41(3):400-411
How to Measure Blood Pressure in Dialysis Patients?
How to Measure Blood Pressure ISH HT 2020
Measure Blood Pressure in Dialysis Patients HD UNIT BP HBPM ABPM (PRE-HD, DURING HD, POST-HD) (HOME BLOOD PRESSURE (AMBULATORY BLOOD MONITORING) PRESSURE MONITORING)
HBPM and ABPM are of greater prognostic value than HD unit BP record -Prospective cohort study -150 HD patients at four university-affiliated units -BP was self-measured at home for 1 wk for an interdialytic interval by ambulatory recording -and by “routine” and standardized methods in the dialysis unit for 2 wk -24 mo F/U -1-SD ↑ in systolic BP -> ↑ risk for death by 1.35 (95% CI 0.99 to 1.84) and -↑in diastolic BP by 1.40 (95% CI 1.03 to 1.93) for home BP Alborzi et al. CJASN 2007;2:1228-1234
Decision making based on HBPM among HD patients lead to better BP control during the interdialytic period in comparison with pre-dialysis BP measurements • RCT, 74 HD patients, mean age 51 yrs, HD vintage 55-60 months, baseline Pre-HD SBP 157-159 mmHg • HBPM group showed significant reduction in SBP compared to the pre-dialysis BP group (weekly mean: 144 ± 21 mmHg versus 154 ± 22 mmHg; P < 0.05) G. Vieira da Silva et al, Nephrol Dial Transplant (2009) 24: 3805–3811
Measure • HD Unit BP: Blood Pressure • Pre-HD SBP > Mean SBP ≈ 10 mmHg in Dialysis • Post-HD SBP < Mean SBP ≈ 7 mmHg Patients • Interdialytic ABPM is the best represent BP in HD patients • Show diurnal variation • Difficult to obtain, more expensive • HBPM is more practical • A period of 1 to 2 weeks BP readings should be used rather than spot readings K/DOQI CPG for cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005;45(4 Suppl 3):S1-153.
Measure …When ambulatory BP monitoring is Blood unavailable Pressure in Dialysis • Use Home BP measurements Patients • taken twice a day • covering interdialytic days • over 1–2 weeks • or twice a day for 4 days following the midweek treatment JE Flythe et al.: BP and volume control in dialysis: a KDIGO conference report
Measure …When ambulatory BP and Home BP are Blood unavailable Pressure in Dialysis • Use BP measurement in-office, not in Patients dialysis unit. • “Subdistrict Health Promotion Hospital (รพ.สต.)” • taken twice a day…at least once a day • covering interdialytic days • over 1–2 weeks JE Flythe et al.: BP and volume control in dialysis: a KDIGO conference report
Increased systolic BP outside of dialysis unit are an independent risk factor for mortality • The spline analyses confirmed linear association. • Association between higher SBP and risk of mortality was statistically significant per every 10 mm Hg increase (HR, 1.26 [95% CI, 1.13–1.39]; P<0.001). Hypertension. 2015 Jan;65(1):93-100.
Measure …When ambulatory BP , Home BP, Blood Subdistrict Health Promotion Hospital Pressure BP are unavailable in Dialysis Patients • Another alternative is mean or median peridialytic BP (pre-, inter-, and post-HD BP) • which has greater sensitivity and specificity in detecting interdialytic hypertension than pre- or post-dialysis BP measurements alone JE Flythe et al.: BP and volume control in dialysis: a KDIGO conference report
Association of Dialysis-Unit SBP and Mortality • Non-linear association (P<0.05). • Spline analyses showed that both low and high ends of the SBP distribution were associated with higher rates of mortality. Hypertension. 2015 Jan;65(1):93-100.
Pathogenesis of Hypertension in Chronic Dialysis Braz. J. Nephrol. (J. Bras. Nefrol.) 2019;41(3):400-411
Pathogenesis of Hypertension in Chronic Dialysis Braz. J. Nephrol. (J. Bras. Nefrol.) 2019;41(3):400-411
Pathogenesis of Hypertension in Dialysis Patients • Sodium and Volume overload • Major cause • Fluid overload of >6% of body weight results in activation of the sympathetic nervous system &↑Cardiac output • when excessive body fluids are removed and “dry-weight” is achieved with slow and more frequent dialysis, BP can be ameliorated in approximately 90% of patients • Sympathetic over-activity • Induced by Fluid overload • ↑Cardiac output and peripheral vascular resistance • Renin-angiotensin-aldosterone system • activate by both impair autoregulation in CKD and UF induced hypovolemia • Endothelial cell dysfunction • Imbalances endothelial-derived hormones (NO-ET1) • ↑ Endothelin 1, ↑Quabain likesubstance, ↓Nitric Oxide, ↓Kinins, ↓Atrial natriuretic peptide • Production of NO is inhibited by ADMA, which accumulates in CKD patients, particularly in those with atherosclerotic complications Am J Kidney Dis. 2010, March ; 55(3): 580–589; Braz. J. Nephrol. (J. Bras. Nefrol.) 2019;41(3):400-411
Pathogenesis of Hypertension in Dialysis Patients • Sleep Apnea • Nocturnal hypoxemia • Activation of the sympathetic nervous system • Reverse Circadian rhythm → ↓Diurnal variation→ No nocturnal dipping →Morning BP surge • Higher LV relative wall thickness • 7.1 times higher risk of developing resistant hypertension • (defined as office BP>140/ 90mmHg despite the use of more than three different antihypertensive agents) Nephrol Dial Transplant (2017) 32: 620–640 Braz. J. Nephrol. (J. Bras. Nefrol.) 2019;41(3):400-411
Pathogenesis of Hypertension in Dialysis Patients • Erythropoietin stimulating agents (ESAs) • IV ESAs (within 30 mins)→ increase in ET1 and rise in MAP • Not demonstrated in subcutaneous route • ↑vasoconstrictive response to endothelin-1 • ↑ sensitivity to the pressor effect of angiotensin II • ↑ blood viscosity • ↑ vascular sensitivity to noradrenergic stimuli • Increase arterial stiffness • mainly related to calcium and phosphate disturbance metabolism resulting in vascular calcification • Parathyroid hormone • Antihypertensive drugs removal by dialysis Am J Kidney Dis. 2010, March ; 55(3): 580–589 Braz. J. Nephrol. (J. Bras. Nefrol.) 2019;41(3):400-411
Pathogenesis of Hypertension in Dialysis Patients • Parathyroid hormone • PTH-induced increases in intracellular calcium →↑vascular response to many vasoconstrictor stimuli & to the activation TGFβ1 stimulation →tissue fibrosis →arterial wall stiffness • PTH activate RAAS system bidirectional link between adrenal cortex and parathyroid glands Hypertension Research volume 34, pages286–288 (2011)
Pathogenesis of Hypertension in Dialysis Patients • Erythropoietin stimulating agents (ESAs) • IV ESAs (within 30 mins)→ increase in ET1 and rise in MAP • Not demonstrated in subcutaneous route • ↑vasoconstrictive response to endothelin-1 • ↑ sensitivity to the pressor effect of angiotensin II • ↑ blood viscosity • ↑ vascular sensitivity to noradrenergic stimuli • Increase arterial stiffness • mainly related to calcium and phosphate disturbance metabolism resulting in vascular calcification • Parathyroid hormone • Antihypertensive drugs removal by dialysis Am J Kidney Dis. 2010, March ; 55(3): 580–589 Braz. J. Nephrol. (J. Bras. Nefrol.) 2019;41(3):400-411
Removal of Antihypertensive drugs
Pathogenesis of Hypertension in Dialysis Patients • Dialysis-specific factors • Sodium • Increase sodium balance → increased thirst, increased interdialytic weight gain, net weight gain, and interdialytic hypertension • Potassium • Low serum potassium → direct vasoconstrictor effect • Calcium • Increase calcium → increases myocardial contractility, decrease arterial compliance Am J Kidney Dis. 2010, March ; 55(3): 580–589 Braz. J. Nephrol. (J. Bras. Nefrol.) 2019;41(3):400-411
Optimal Target Blood Pressure in Dialysis Patients ??
Target BP in Dialysis Patients in K/DOQI Guidelines K/DOQI 2005 guidelines on cardiovascular disease in dialysis patients • Predialysis and postdialysis blood pressure goals should be <140/90mmHg and <130/80mmHg respectively (C) K/DOQI 2006 hemodialysis adequacy guidelines • Focus on volume control, dietary sodium restriction and avoid high dialysate sodium • DO NOT recommend specific blood pressure targets in hemodialysis patients K/DOQI 2007 clinical practice guidelines for diabetes and CKD • Target blood pressure in diabetes and CKD stages 1-4 should be <130/80mmHg (B) • Targets for patients on dialysis are not recommended. K/DOQI 2015 Clinical Practice Guideline for Hemodialysis Adequacy • Reducing dietary sodium intake as well as adequate sodium/water removal with HD • DO NOT recommend specific blood pressure targets in hemodialysis patients
Target Blood Pressure in Dialysis Patients as Guidelines Guideline Blood Pressure Target KDOQI 2005 Guidelines Pre-dialysis BP <140/90 mm Hg Post-dialysis BP <130/80 mm Hg KDOQI 2015 Guideline Update No target defined, citing paucity of clinical trial data Canadian Society of Nephrology 2006 Pre-dialysis BP <140/90 mm Hg Guidelines European ERA-EDTA 2017 Guidelines No target defined, citing paucity of clinical trial data Japanese Society for Dialysis Therapy 2012 Pre-dialysis BP <140/90 mm Hg Guidelines
Target Blood Pressure in Dialysis Patients • No consensus BP target due to lack of high-grade evidence • An individualized approach is priori necessary for all patients, • with focus on avoiding overly low BPs, and • special consideration regarding intradialytic and interdialytic BP patterns, volume management, and comorbidities • Maybe practice in range of BP target more than a specific number • Pre-dialysis SBP ~ 140-160 mmHg • Post-dialysis SBP ~ 120-140 mmHg (from observational study + small RCT) Luther JM. Kidn Int 2008;73:667-668 JE Flythe et al. Kidney International (2020) 97, 861–876
Management of Hypertension in Dialysis patients
Hypertension W/U 2nd Causes Management Algorithm KDOQI 2005 in Dialysis Patients Guidelines for Cardiovascular Disease in Dialysis Patients
Hypertension W/U 2nd Causes Management Algorithm KDOQI 2005 in Dialysis Patients Guidelines for Cardiovascular Disease in Dialysis Patients
Lifestyle Modification and Achieve Dry Weight Hypotension ↑Serum ↑Dialysate with Na Na Saline tx Chronic Volume ↑Thirst Non- Overload optimal Am J Kidney Dis. 2015;66(5):884-930 Dry weight ↑Water KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients Intake
Lifestyle Modification and Achieve Dry Weight Hypotension ↑Serum ↑Dialysate • Restrict Na intake<2gm/d or with Na NaCl<5 gm/d Na Saline tx Chronic • Restrict Fluid intake : Volume ↑Thirst No RRF: 600-800 ml/day Non- Overload With RRF: RRF + insensible loss optimal Dry weight ↑Water Intake Am J Kidney Dis. 2015;66(5):884-930 KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients
Lifestyle Modification and Achieve Dry Weight Hypotension ↑Serum ↑Dialysate • Low dialysate Na down to with Na 135 mEq/L Na Saline tx Chronic Volume ↑Thirst Non- Overload optimal Dry weight ↑Water Intake Am J Kidney Dis. 2015;66(5):884-930 KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients
Effect of Lowering Dialysate Sodium and BP Am J Kidney Dis. 2015;66(5):884-930
Lifestyle Modification and Achieve Dry Weight ↑Serum Na Hypotension ↑Dialysate • Dry weight reduction: with 0.2kg/session- Na 0.1kg/10kg/session Saline tx Tool guided mx: BVM, BCM, Chronic Lung US Non-optimal Volume Dry weight Overload ↑Thirst • Prolong/Slow UF dialysis to ↑Water achieve Dry Wt: Intake > 4-12 weeks, add time/wk Am J Kidney Dis. 2015;66(5):884-930 KDOQI 2005 Guidelines for Cardiovascular Disease in Dialysis Patients
Dry-weight Reduction in Hypertensive Hemodialysis Patients (DRIP trial) • Additional volume reduction will result in improvement in BP among hypertensive patients on hemodialysis • Randomized in 1:2 in control group vs. UF trial group for 8 weeks Weight loss 0.1 kg/10 kg per dialysis, not increase time or frequency If not tolerate → ↓weight loss 50% until 0.2 kg/session → achieve Dry Wt No changes in anti-HT medication during the trial • Inclusion : Age > 18 yr, 3x/week HD ≥ 3 month with mean inter-dialytic ambulatory BP ≥ 135/85 mmHg • Exclusion : Previous stroke, MI or limb ischemia within 6 months, ambulatory BP >170/100 mm Hg, chronic AF or morbid obesity • Outcome : Change in ambulatory BP Agarwal et al. Hypertension 2009; 53: 500-507
Dry-weight Reduction in Hypertensive Hemodialysis Patients (DRIP trial) • At 4 weeks reduced 0.9 kg, resulted in -6.9 mm Hg change in SBP (95% CI: 12.4 to 1.3 mm Hg; P0.016) and -3.1 mm Hg change in DBP (95% CI: 6.2 to 0.02 mm Hg; P0.048). • At 8 weeks, DW was reduced 1 kg, SBP changed -6.6 mm Hg (95% CI: 12.2 to 1.0 mm Hg; P0.021), and DBP changed -3.3 mm Hg (95% CI: 6.4 to 0.2 mm Hg; P0.037) from baseline. Agarwal et al. Hypertension 2009; 53: 500-507
Lifestyle Modification and Achieve Dry Weight • Beware of “Lag phenomenon” • Blood pressure is normalized a few weeks to month after ECV is returned to normal, i.e. when the patient reaches dry weight ADMA = Asymmetrical dimethyl-L-arginine DDAH = dimethylarginine dimethylaminohydrolase American Journal of Kidney Diseases, Vol 43, No 4 (April), 2004: pp 739-751
Lifestyle Modification and Achieve Dry Weight • Beware of “Lag phenomenon” • Blood pressure is normalized a few weeks to month after ECV is returned to normal, i.e. when the patient reaches dry weight OLC = Ouabain-like compound DLIS = digoxin-like immunoreactive substance American Journal of Kidney Diseases, Vol 43, No 4 (April), 2004: pp 739-751
Relative Blood Volume Monitoring (BVM) • Fluid removal during dialysis (Ultrafiltration, UF) → Red Blood Cell concentration • In online HDF machine • Which can be continuously measured by optical sensors • Slope of BVM change may predict development of IDH • Significant reduction in IDH and faster recoverytime after dialysis
Bioelectrical Impedance Analysis (BIA) Journal of Sensors and Sensor Systems.2017 6(2):303-325
Bioelectrical Impedance Analysis (BIA) With permission from patient
LUNG ULTRASONOGRAPHY ▪c“oBm-elintse”s” or “Comet tail sign” or “Lung ▪ Total 28 sites of intercostal spaces ▪ Score 0 -10/site ▪ 3 categories of increasingly severe pulmonary congestion: ❖ none or mild: <16 comets ❖ moderate: 16–30 comets ❖ severe: >30 comets
ONGOING RESEARCH Comparison between Lung Ultrasonography and Clinical Assessment for Volume Control in Chronic Hemodialysis Patients • HD patients ≥ 18 - 80 years • HD ≥ 3 months • Mean BP ≥ 135/85 mmHg or on Anti-HT drugs ≥ 1 Primary Outcome: blood pressure (BP) control Secondary Outcome: anti-HT drug use, CT ratio, safety and complications, compare withBIA Sawinee Kongpetch, Akeatit Trirattanapikul, Eakalak Lukkanalikitkul, Anucha Ahooja, Sirirat Anutrakulchai
RESEARCH METHODOLOGY EXCLUSION CRITERIA Due to LUS measurement limitation • active CV diseases in 6 months • known persistent pleurisy • pulmonary fibrosis • NYH III-IV, LVEF<40% • ACS, severe VHD, massive pericardial effusion • stroke • pneumectomy • autonomic dysfunction Due to BIA assessment limitation • morbid obesity • metallic joint prostheses • malignancy • cardiac stent or pacemakers • active infections • decompensated cirrhosis • temporary or permanent catheter as a vascular access • pregnancy • mental incompetence • limb amputations • unwillingness to participate in the study
RESEARCH 40 patients METHODOLOGY randomization Lung US* Clinical assessment ≤ 15 B-lines 16-30 B-lines > 30 B-lines * Controlled by No change ↓Dry Weight ↓ Dry Weight radiologist staff + 0.05kg/BW10kg/2wk 0.1kg/BW10kg/2wk Lung US + + q 1 wk Lung US Lung US q 1 wk q 1 wk Home SBP/DBP 48 hr at Mon-0 Mon-1 Mon-2 Observe complications (intradialytic hypo/hypertension, muscle cramp, hospitalization) NT-Pro BNP, TNT at Mon-0, Mon-2 CXR, BIA, CAVI at Mon-0, Mon-2
Home Systolic Blood Pressure 150 *P=0.009 *P=0.011 145 146.19 140 143.09 142.36 142.93 135 SBP, mmHg 130 134.45 136.54 125 120 MONTH-1 MONTH-2 115 110 105 100 MONTH-0 LUS Clinical * Adjusted with baseline SBP (Month 0) Groups Month-0 Month-1 Month-2 LUS 146.19 134.45 136.54 Clinical 143.09 142.36 142.93 mean difference *9.57 *8.95 P-value *0.009 *0.011
Decrease Dose of Anti-HT Drugs 70% 60% P =0.002 60% 50% Percentage 40% 30% 20% 10% 10% 0% LUS Clinical
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