Peridialytic, Intradialytic, and Interdialytic Blood Pressure Measurement in Hemodialysis Patients

Among hemodialysis (HD) patients,1 hypertension is highly prevalent and frequently uncontrolled. Treatment of HD patients with antihypertensive medications is associated with improved cardiovascular outcomes.2, 3 Cardiovascular disease is a leading cause of death in HD patients.4 Nonetheless, there is no consensus about whether to lower increased blood pressure (BP) in HD patients or the level to which BP should be targeted.5, 6 This is caused in large part by difficulties associated with accurate assessment of BP in HD patients.7, 8, 9, 10

BP measurement among HD patients can be obtained by 3 methods. These methods include peridialytic, intradialytic, and interdialytic measurements. Peridialytic BP measurements form the basis of the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines11 and are used for management of hypertension in the majority of HD patients today; these are the BP measurements performed by dialysis unit staff shortly before and after the HD session. Thus, peridialytic BP recordings, which are often obtained without attention to method of measurement, have been used in the large cohort studies that have found a reverse epidemiology, in which lower BP has been associated with higher mortality rates in HD patients.6, 12, 13 Routine peridialytic BP recordings are highly variable and poorly reproducible, whether these assessments are performed in carefully controlled research settings or larger epidemiologic studies.14, 15 Even when assessed using standard measurement methods, peridialytic BP recordings do not correlate well with end-organ damage, such as left ventricular hypertrophy or cardiovascular outcomes.16, 17 Cohort studies suggest that achieving recommended peridialysis BP targets is associated with increased frequency of intradialytic hypotension.18 Not surprisingly, there is poor agreement between routine peridialytic BP and the gold standard of BP measurement, interdialytic ambulatory BP monitoring.8

The diagnostic performance of peridialytic BP recordings can be improved by consideration of intradialytic recordings.19 Intradialytic BP is a recording made during HD, typically every 30 minutes, using an automatic cuff attached to the HD machine. Diagnosing hypertension using ambulatory BP as a gold standard, average intradialytic BP considered together with peridialytic BP has greater diagnostic value compared with peridialytic BP recordings alone.19 However, because calculating an average is time consuming and impractical at the bedside, median intradialytic BP (which is an adequate measure for central tendency and is close to the mean in normally distributed data) from a single HD session also appears appropriate for the diagnosis of hypertension. It is possible that intradialytic BP correlates better with ambulatory BP than peridialytic BP because the latter, similar to interdialytic BP, samples the patient during a range of extracellular fluid volume and uremic states, albeit during the condensed time span of the HD session.

The third type of BP measurement is interdialytic, which can be obtained using ambulatory BP monitoring or self-measurement by the patient using home BP monitoring.20, 21, 22 Regardless of the technique of interdialytic BP assessment, these measurements appear to carry greater prognostic information compared with peridialytic recordings.17 For example, interdialytic ambulatory BP is valid23 and reproducible,24 correlates with echocardiographic evidence of left ventricular hypertrophy,16 and is a predictor of increased mortality in HD patients.17 Similarly, increased home BP has correlated with left ventricular hypertrophy and increased cardiovascular and all-cause mortality in HD patients.16, 17 The superiority of these methods is not dependent on only their greater number of measurements because interdialytic BP measures retain their correlation with all-cause mortality, even if a smaller number of randomly chosen measurements are analyzed.25 It is believed that interdialytic BP measurements are superior because they provide a more accurate reflection of the patient's BP burden over time, and this burden is sampled over the range of extracellular fluid volume and uremic states, from the nadir shortly after an HD session to the zenith just before the next HD session.26, 27 Ambulatory BP monitoring can be cumbersome for some patients to perform, which is perhaps the main reason that the readily available peridialytic BP is still the primary measure used for diagnosing and treating hypertension in HD patients. However, home BP measurement changes also track well with changes in ambulatory BP recordings; therefore, home BP can be used to make therapeutic decisions.28

In this issue of the American Journal of Kidney Diseases, Inrig et al29 report that increasing peridialytic systolic BP in incident HD patients with normal pre-HD systolic BP is significantly associated with increased mortality at 2 years. This observation comes on the heels of a post hoc analysis of a randomized trial in which Inrig et al reported increased 6-month mortality rates with increasing peridialytic systolic BP.30 Given that both are observational studies, which do not prove cause and effect, interpretation of these findings requires 2 approaches. The questions we pose are the following: first, if the findings are causally related, why should they be so; and second, if the findings are unrelated, what could underlie the observations.

We, like the authors, cannot think of a plausible direct causal link between increasing BP and increased mortality. It thus follows that the observed increase in mortality would not be mitigated if the increase in peridialytic BP were prevented through such measures as predialysis use of antihypertensive medications.

If the findings are causally unrelated, there are several possible reasons for this association (Box 1). First, as the authors speculate, increasing BP may be a manifestation of endothelin excess that is associated with endothelial dysfunction and atherosclerosis, which may manifest in the observed increased mortality.31 Second, the observed increase in mortality was limited to patients with low-normal pre-HD BP who also had increasing peridialytic BP. These patients often are clinically dwindling because of advanced chronic disease. Patients with increasing peridialytic systolic BP are noted by Inrig et al29 to have significantly lower interdialytic weight gain and serum phosphorus levels, consistent with decreased oral intake. Similarly, these patients have significantly lower body mass index and serum creatinine levels, consistent with more wasting than patients without an increase in peridialytic BP. Also, they are noted to have significantly lower serum albumin levels, consistent with more inflammation. Perhaps the increased mortality in this population is caused by advanced chronic illness that is not accounted for in statistical adjustments.32 Third, patients with normal pre-HD systolic BP also may be more prone to intradialytic hypotension than the rest of the HD population, which might in turn be prevented or treated with hypernatremic dialysate, frequent cessation of ultrafiltration, and saline infusions. These interventions can result in increased post-HD systolic BP and leave the patient volume overloaded, which itself is another potential cause of the observed increased mortality. Unfortunately, intradialytic BP recordings were not available for investigation of intradialytic hypotensive episodes. Fourth, if these patients start HD with normal systolic BP and finish with a higher systolic BP, their systolic BP must necessarily decrease in the interdialytic period to a normal value before their next HD session. This decreasing BP in the interdialytic period is a potential marker of volume excess.33 Given the study design, we do not have measurements of volume state or level of left ventricular function, either of which can predict mortality.34 Fifth, we do not know how reproducible the observed increases in peridialytic BP values are because they are from only 3 consecutive HD sessions, and peridialytic BP recordings are prone to high variability.24

Box 1. Possible Explanations for the Association Between Increasing Peridialytic BP and Mortality in Patients With Low-Normal Pre-HD Systolic BP

	1.Increasing BP is a marker of endothelial dysfunction. 2.Low pre-HD BP is a marker of advanced chronic illness. 3.Low pre-HD BP is a marker of susceptibility to intradialytic hypotension, which, when treated, leads to volume overload. 4.Increasing peridialytic BP is itself a marker of volume overload. 5.Increasing peridialytic BP is not reproducible within a given patient; therefore, the observed association with mortality is a random event.

Abbreviations: BP, blood pressure; HD, hemodialysis.

Not withstanding these limitations, the report by Inrig et al29 is important because it calls attention to BP assessment in HD patients and looks beyond conventional peridialytic BP to analyzing patterns of peridialytic BP. Whereas interdialytic ambulatory BP measurement is the gold standard for the diagnosis of hypertension in HD patients, its implementation can be difficult, and it is not readily available in most HD units. Routine use of peridialytic BP measurement represents the other end of the spectrum because these BP recordings are obtained easily, but have less reproducibility and utility. The median value from intradialytic BP measurements and peridialytic BP recordings may represent an acceptable compromise between utility and practicality.

With respect to intradialytic BP measurements, additional studies are required on multiple fronts. First, larger studies are needed to confirm the diagnostic performance of intradialytic BP recordings. Second, it is unknown whether intradialytic BP correlates with end-organ damage or hard outcomes, such as cardiovascular events and mortality. Third, because this study focuses on the pattern of peridialytic BP and patterns of interdialytic ambulatory BP appear to be associated with volume status and arterial stiffness,35 the pattern of intradialytic BP warrants further investigation.

There still is no consensus on the best overall measure of BP in HD patients from the point of view of patients, practitioners, or the health care system. However, based on current evidence, we must look beyond routine peridialytic BP. Intradialytic BP is a candidate for a compromise between scientific rigor and everyday ease of use. However, a paradigm shift appears to be indicated when managing hypertension among hemodialysis patients36; BP values obtained during dialysis should be used to ensure hemodynamic stability, and home BP measurement should be used to diagnose and treat hypertension.3, 37