Hypertension and Hemodialysis

Rationale

Of all modifiable risk factors for mortality, and especially cardiac deaths, the greatest benefit has been shown for BP lowering. BP in patients on HD possesses several unique features, and wide fluctuations occur during dialysis and in the interdialytic interval. The aim of treatment outlined in this guideline includes:

1. Optimizing BP control avoiding hypotension

2. Obtaining maximum cardiovascular benefits and quality of life.

Recommendations

• BP control is an important component of comprehensive evaluation of cardiovascular status and all dialysis patients benefit from this. We suggest that ABPM is the ideal tool for measuring BP

• We recommend that MHD patients should have BP monitoring at peridialytic period (predialysis BP, postdialysis BP, and intradialytic) and during the interdialytic interval.

• We recommend that BP should be monitored every hour during dialysis session in stable patients and more frequently in unstable patients.

• The target goals need to be individualized and targeted to achieve lowest possible home BP with least symptoms (hypotension and cramps) during intradialytic period as well as after HD.

• Postdialysis BP target of <130/80 mmHg and predialysis BP <140/90 mmHg are recommended (KDOQI 2005)

• Recommendations are to measure:

  • Interdialysis home BP and target at <140/90 mmHg.
  • Mean AMBP is recommended in patients with variable BP levels during dialysis, should be targeted at <135/85 mmHg during day and <120/80 mmHg during night.

Therapeutic interventions to achieve target blood pressure

Nonpharmacologic

• We recommend that maximum efforts be made to achieve target dry weight: the lowest tolerated postdialysis weight, at which the patient experiences minimal symptoms of either hypovolumeia or hypervolumia

• We recommend that the clinician must try to set a “target dry weight” based on clinical assessment and achieve that weight over 3–6 weeks in young adults and 12–14 weeks in older individuals and those with vascular pathology.

• Control of volume status: During dialysis procedure, we recommend aiming at gradual removal of fluid over a period of days to weeks until a stable “dry weight” is achieved. Control of volume status is fundamental for BP control in dialysis population. It can either normalize the BP or make the HTN easier to control in the great majority of dialysis patients.

  • We recommend accurate setting of the clinical “dry weight” – the weight below which further UF will always produce hypotension and symptoms such as cramps, nausea, and vomiting. The “dry weight” is highly variable in many patients and can fluctuate with intercurrent illnesses (such as diarrhea or infection) as well as nutritional status.
  • We suggest an iterative “trial-and-error” method of dry weight assessment in assessing volume status. Numerous attempts have been made to utilize alternative methods to more accurately assess dry weight. Bioimpedance plethysmography and relative plasma volume (RPV) measurement are considered reliable methods.

• Patients should be adequately dialyzed (please see dialysis adequacy)

• We recommend that short duration of dialysis <4 h/session should be avoided.

• We recommend that large interdialytic weight gains must be discouraged by managing fluid and salt intake.

• We recommend trying to achieve a low sodium intake (<1.5 g of sodium or <4 g of sodium chloride per day), in consultation with the dietician.

• We recommend a maximum hourly UF rate not exceeding 10 ml/kg/h

• Use of more frequent or prolonged dialysis treatments is recommended to remove fluid.

• The single most important cause of HTN in CKD and dialysis patients is sodium and volume excess due to diminished sodium excretory capacity. Prevalence of HTN is around 86% at the time of initiation of HD. After initiation of dialysis, prevalence reduces to 50%– 60% based on multiple studies, due to correction of various pathophysiological factors, mainly better degree of volume control.

  Other methods used are the IVC diameter and plasma natriuretic peptide (particularly atrial and brain) concentrations. However, these methods are frequently impractical and are not necessarily accurate and a large prospective study has not yet been performed that compares these methods to clinical assessment alone. The clinician must therefore define the dry weight and goal BP for each dialysis patient based on his or her best clinical judgment.

• Few studies using long slow hemodialysis of 8 hour long sessions thrice weekly demonstrated that normotension could be achieved without medications in almost all patients Although these results have been largely attributed to optimal volume control, other factors may also contribute, such as better control of uremia which, as noted above, may decrease afferent renal nerve activity and efferent sympathetic activation.

• Nocturnal hemodialysis: A procedure in which dialysis is performed six or seven nights a week during sleep for a variable amount of time (usually 6–12 h in total), which is also associated with excellent BP control. Almost all patients become normotensive without medications. To achieve this, the “target weight” is progressively decreased until all antihypertensive agents are discontinued.

• We recommend that the target hematocrit should be achieved slowly by starting with low initial doses of EPO.

• We recommend that antihypertensive drugs used before the initiation of dialysis may have to be titrated and reduced or withdrawn depending on BP control once dialysis is started and hypervolemia is improved.

• We suggest that patients who have difficulty in achieving “target dry weight” or whose BPs are labile or develop (LVF) left ventricular failure despite achieving dry weight should be evaluated by echocardiography, bioimpedence, plethysomography, RPV measurements, IVC diameters, plasma or brain natriuretic peptide levels, and and true dry weight.

• Dry weight is dynamic, and we suggest that frequent clinical assessment must be made to reassess dry weight.

Discussion and pathogenesis

• HTN is associated with an increased risk of left ventricular hypertrophy, coronary artery disease, cardiomyopathy, and overall mortality.

• Direct correlation between systolic BP (SBP) and total mortality and cardiovascular events

• U curve correlation between cardiovascular mortality and predialysis SBP. Mortality increases when predialysis SBP <110 mmHg or >180 mmHg.

• Only 30% of dialysis population has well-controlled BP and 12% have untreated HTN.

Method of blood pressure measurement

• Immediate predialysis and/or postdialysis BP measurements are imprecise estimates of mean interdialytic BP. The predialysis SBP may overestimate the mean interdialytic SBP by 10 mmHg, while the postdialysis SBP may underestimate the mean SBP by 7 mmHg. The main aim of peridialysis BP measurement is to ensure hemodynamic stability during dialysis.

• We recommend the use of home BP measurement and AMBP for diagnosing and managing HTN. Studies indicate that these are superior in terms of HTN diagnosis, management, and prognostication.

• Home BP measurements are

  • More reproducible
  • Correlates better with AMBP
  • Better predictor of long-term outcomes such as cardiovascular morbidity and mortality

• We recommend that home BP measurement is performed for continuous 7 days with twice-daily readings, in the morning before medication and evening before dinner.

• We recommend the use of ABPM in patients not achieving target BP control or having large variation in readings; intradialytic hypotension and postdialytic HTN.

• We recommend that AMBP is monitored over the entire interdialytic interval (44 h), every 20 min from 6 a.m. to 10 p.m., every 30 min from 10 p.m. to 6 a.m.

• We recommend that readings should be performed using standardized technique^a that follows the guidelines of adequate rest before measurement, an appropriate cuff size, and a validated and calibrated oscillometric or aneroid device.

Optimal blood pressure

Current BP target ranges for dialysis patients have been extrapolated from those suggested for the nondialysis patient population.

We recommend the NKF/KDOQI 2005 targets shown in Table 1.

Table 1.

Target blood pressures in dialysis patients

Predialysis BP	Postdialysis BP	Mean interdialytic BP	Mean AMBP
<140/90 mmHg	<130/80 mmHg	SBP 120-135 mmHg DBP 85-90 mmHg	<135/85 mmHg during day <120/80 mmHg during night

BP: Blood pressure, DBP: Diastolic BP, SBP: Systolic BP, AMBP: Ambulatory BP monitoring

Treatment

a Standardized BP protocol: This involves BP measurement in seated position, after rest for at least 5 min, in triplicate, with adequately sized cuff and a validated and calibrated monitor. If BP measurements are made in thigh, owing to restrictions of upper arm use, supine reading should be used (with the thigh at the level of heart) to avoid incorrect high values because of the body position.

Pharmacologic

• If the BP remains elevated despite the attainment of “dry weight,” antihypertensive medications should be administered.

• We suggest that the choice of drug should be individualized based on the safety, efficacy, and pharmacokinetic properties of the drug and benefits and comorbid conditions of the patient. An antihypertensive agent is preferably administered during the evening with a once-per-day dosing schedule.

Antihypertensive medications

Therapy with antihypertensive drugs is primarily indicated in 25%–30% of dialysis patients in whom HTN persists despite seemingly adequate volume control. Beta-blockers, angiotensin II receptor blockers (ARBs), angiotensin converting enzyme inhibitor (ACE-I), calcium channel blockers (CCBs) and MRA have been shown to reduce cardiovascular morbidity and mortality in dialysis patients.

We recommend that beta-blockers and CCB blockers are preferred classes of antihypertensive drugs. Beta-blockers have best clinical evidence in terms of reduction of cardiovascular morbidity and mortality and CCBs have best safety profile and are very effective.

We suggest that antihypertensive therapy may need to be individualized and a selection may be made from among the classes of drugs listed below.

• a)CCBs: CCBs are both effective and well tolerated in dialysis patients, even in those who are volume expanded. The only randomized prospective study found that amlodipine, compared with placebo, improved overall mortality among hypertensive dialysis patients. These drugs are particularly useful in patients with left ventricular hypertrophy and diastolic dysfunction. CCBs have unaltered pharmacodynamics and little dialysability, with no supplemental doses needed after dialysis and once-daily dosing is suffice.
• b)ACE inhibitors: ACE inhibitors are well tolerated and are particularly effective in patients with heart failure due to systolic dysfunction and in many patients after an acute MI. These agents may help preserve native kidney function. The evidence of cardiovascular benefits is not as robust as in the general population. ACE inhibitors are associated with a decrease in left ventricular mass among HD patients. There are conflicting data concerning the effect of ACE inhibitors on mortality among hypertensive patients undergoing MHD. Fosinopril and perindopril are nondialyzable among ACE-I drugs.
• c)ARBs: A number of ARBs are currently available. Among HD patients, ARBs have independent cardiovascular benefits in heart failure and post MI patients. Evidence suggest that these drugs preserve residual renal function. Most ARBs are not dialyzable, so preferred over ACE-I in dialysis population.
• d)Beta blockers – We suggest that beta blockers are particularly indicated in patients with established coronary artery disease (recent MI and patients with end-stage renal disease (ESRD) who have heart failure due to systolic dysfunction). Beta blockers attenuate sympathetic overactivity and prevent ventricular arrthymias and sudden deaths.

  We suggest the use of nondialyzable (bisoprolol and carvidelol) beta blockers.

• e)The central sympathetic agonists such as methyldopa and clonidine are used less frequently because of their adverse effects involving the CNS.

Reduced dialysate sodium concentration

We suggest that a variable dialysate sodium concentration may result in lower antihypertensive medication requirements and decrease in postdialysis BP. Gradual reduction in dialysate sodium concentration from standard of 138–140 mEq/l to 135 mEq/L reduces thrist and lowers interdialytic weight gain and in combination with dietary salt restriction may also help control HTN.

Refractory hypertension

We suggest that in dialysis patients with resistant to both volume control and antihypertensive medications, the following factors be considered:

• Concurrent use of a medication that can raise the BP (such as nonsteroidal anti-inflammatory drugs),

• Renovascular HTN,

• Noncompliance to medical regimen and expanding cyst size in polycystic kidney disease.

• If a treatable cause cannot be found, minoxidil may be effective in reducing the BP. We suggest that patients undergoing HD who are noncompliant and in whom volume status and HTN cannot be controlled may also benefit by switching to peritoneal dialysis. Nearly all peritoneal dialysis patients can become normotensive with strict adherence to volume control. The efficacy of peritoneal dialysis in controlling BP in refractory patients is related to its smoother volume removal and its more consistent maintenance of dry weight.

Paradoxical (intradialytic) hypertension

We suggest that paradoxical HTN be considered in patients after ruling out all the above causes. Although hypotension during HD is a frequent complication, some patients develop paradoxical HTN in the later stages of dialysis, a time at which most of the excess fluid has already been removed. This problem is intermittent in a given patient with a widely variable frequency. The pathogenesis is unclear, some presumed causes are excess UF leading to hypovolemia and sympathetic overacitivity, removal of antihypertensive drugs, improvement of hypoxia, and high hematocrit. Sometimes, the administration of isotonic saline to presumably treat hypovolemia may be helpful. 10-mg nifedifine may be used to lower BP.