Blood pressure and volume management in dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Blood pressure (BP) and volume control are critical components of dialysis care and have substantial impacts on patient symptoms, quality of life, and cardiovascular complications. Yet, developing consensus best practices for BP and volume control have been challenging, given the absence of objective measures of extracellular volume status and the lack of high-quality evidence for many therapeutic interventions. In February of 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference titled Blood Pressure and Volume Management in Dialysis to assess the current state of knowledge related to BP and volume management and identify opportunities to improve clinical and patient-reported outcomes among individuals receiving maintenance dialysis. Four major topics were addressed: BP measurement, BP targets, and pharmacologic management of suboptimal BP; dialysis prescriptions as they relate to BP and volume; extracellular volume assessment and management with a focus on technologybased solutions; and volume-related patient symptoms and experiences.The overarching theme resulting from presentations and discussions was that managing BP and volume in dialysis involves weighing multiple clinical factors and risk considerations as well as patient lifestyle and preferences, all within a narrow therapeutic window for avoiding acute or chronic volume-related complications. Striking this challenging balance requires individualizing the dialysis prescription by incorporating comorbid health conditions, treatment hemodynamic patterns, clinical judgment, and patient preferences into decision-making, all within local resource constraints.
Qualitative data suggest that suboptimal BP and volume management negatively affect quality of life. [bib_ref] Developing a set of core outcomes for trials in hemodialysis: an international..., Evangelidis [/bib_ref] [bib_ref] Perspectives on symptom experiences and symptom reporting among individuals on hemodialysis, Flythe [/bib_ref] [bib_ref] Symptoms among patients receiving in-center hemodialysis: a qualitative study, Cox [/bib_ref] Efforts to develop consensus best practices in managing BP and volume in dialysis have been hampered by an absence of widely available, accurate, and objective measures of extracellular volume status, as well as a lack of high-quality evidence. As such, related practice patterns vary considerably, both within local communities and throughout the world.
In February 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference, Blood Pressure and Volume Management in Dialysis, in Lisbon, Portugal (https://kdigo.org/conferences/bp-volume-management-in-dialysis/). The conference is the second of 4 conferences planned on dialysis (see Chan et al. [bib_ref] Dialysis initiation, modality choice, access, and prescription:conclusions from a Kidney Disease: Improving..., Chan [/bib_ref] for the first report, on dialysis initiation). Participants, who included both physicians and patients, considered how BP and volume management can be optimized and individualized across dialysis modalities and resource settings.

## Major themes
As participants addressed specific issues relating to BP and volume in dialysis, multiple crosscutting themes emerged. First was the substantial heterogeneity of the dialysis population (e.g., incident vs. prevalent status, comorbid conditions, residual kidney function , and nutritional status) and the treatment setting (in-center vs. home therapies, medication use, etc.) that must be considered when prescribing dialysis. Second was the ever-present tension in balancing multiple, interlinked, volume-related factors within a narrow therapeutic window for avoiding complications. In some instances, correcting one volume-related abnormality (e.g., hypervolemia) may result in increasing risk associated with another volume-related parameter (e.g., ultrafiltration [UF] rate and RKF). Data to guide these decisions are limited. Third was recognition of the impact that poorly managed BP and volume have on patient lives, and the importance of incorporating patient priorities into management decisions. Fourth, availability of local resources and technologies vary globally and often dictate the bounds of dialysis prescriptions. Therefore, individualizing the dialysis prescription to manage BP and volume for each patient and setting is essential and requires incorporating numerous factors into decision-making. Finally, there was broad-based recognition of the lack of quality evidence to inform recommendations for the management of many of the BP and volume complications discussed, resulting in few strong recommendations, and calls for additional research. In many regions of the world, the dialysis community is well positioned to fill these knowledge gaps. Investigators and dialysis organizations must collaborate to leverage the predictable nature of dialysis treatments, large volumes of collected data, and research and clinical implementation capacities inherent to well-resourced dialysis delivery systems to address these fundamental questions.
observational studies have shown that pre-and post-dialysis BP have either no association or a U-or J-shaped association with mortality. [bib_ref] Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves..., Foley [/bib_ref] [bib_ref] Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis..., Robinson [/bib_ref] [bib_ref] The optimal blood pressure target in different dialysis populations, Jhee [/bib_ref] These findings may stem in part from the inaccuracy of pre-and post-dialysis BP measurements. Pre-and post-dialysis BPs, even if measured using a standardized protocol, are imprecise estimates of interdialytic BPs [bib_ref] Pre-and postdialysis blood pressures are imprecise estimates of interdialytic ambulatory blood pressure, Agarwal [/bib_ref] and generally should not be used alone for diagnosing and managing hypertension. However, pre-, post-(i.e., peridialytic), and intradialytic BP measurements do have clinical importance for assessing and managing hemodynamic stability during the HD session.
Ambulatory BP monitoring is considered the gold-standard method for BP evaluation. [bib_ref] Hypertension in chronic kidney disease part 1: Out-of-office blood pressure monitoring: Methods,..., Parati [/bib_ref] [bib_ref] Assessment and management of hypertension in patients on dialysis, Agarwal [/bib_ref] [bib_ref] Hypertension in dialysis patients: a consensus document by the European Renal and..., Sarafidis [/bib_ref] Compared with peridialytic BP, 44-hour interdialytic BP has superior risk prediction for allcause and cardiovascular mortality. [bib_ref] Home blood pressures are of greater prognostic value than hemodialysis unit recordings, Alborzi [/bib_ref] Ambulatory BP monitoring use may be limited by patient intolerance, availability, and financial constraints in some countries. [bib_ref] Hypertension in dialysis patients: a consensus document by the European Renal and..., Sarafidis [/bib_ref] When ambulatory BP monitoring is unavailable, home BP measurements may be taken twice a day, covering interdialytic days over 1-2 weeks or twice a day for 4 days following the midweek treatment. [bib_ref] Hypertension in dialysis patients: a consensus document by the European Renal and..., Sarafidis [/bib_ref] [bib_ref] Chronobiology of arterial hypertension in hemodialysis patients: implications for home blood pressure..., Agarwal [/bib_ref] Compared with peridialytic BP measurement in HD, home BP measurement has superior agreement with mean 44-hour ambulatory BP monitoring, [bib_ref] Home blood pressure monitoring improves the diagnosis of hypertension in hemodialysis patients, Agarwal [/bib_ref] higher short-term reproducibility, [bib_ref] Home blood pressure measurements for managing hypertension in hemodialysis patients, Agarwal [/bib_ref] and improved prediction of adverse outcomes. [bib_ref] Home blood pressures are of greater prognostic value than hemodialysis unit recordings, Alborzi [/bib_ref] Key disadvantages of home BP monitoring are the absence of information on nocturnal dipping, and in some settings, cost.
A third alternative is BP measurement in-office, not in the dialysis unit. Increased systolic BPs (SBPs) outside of the dialysis unit are an independent risk factor for mortality. [bib_ref] Blood pressure and risk of all-cause mortality in advanced chronic kidney disease..., Bansal [/bib_ref] Another alternative is mean or median peridialytic BP (pre-, inter-, and post-HD BP values), which has greater sensitivity and specificity in detecting interdialytic hypertension than preor post-dialysis BP measurements alone. [bib_ref] Diagnosing hypertension by intradialytic blood pressure recordings, Agarwal [/bib_ref] However, no studies have assessed the association of this approach with outcomes.
Data assessing the validity of peridialytic, office, and home BP in patients receiving home HD or peritoneal dialysis (PD) are limited, and no studies have been conducted in these populations on the associations of out-of-unit BP measurements and the risk of cardiovascular outcomes. Research to identify valid methods for BP measurement in all dialysis modalities is recommended .

## Definition of hypertension and bp treatment targets
Accepted definitions of hypertension and BP treatment targets in the dialysis population have not been determined, with just one relevant randomized controlled trial (RCT). The Blood-Pressure-in-Dialysis pilot (BID) study randomized 126 participants to either an intensive pre-dialysis SBP goal of 110-140 mm Hg or a standard SBP goal of 155-165 mm Hg, with the primary objective of assessing feasibility and safety to inform a larger RCT assessing hard clinical outcomes. [bib_ref] BP in dialysis: results of a pilot study, Miskulin [/bib_ref] The study demonstrated intervention feasibility; however, despite the protocol calling for site investigators to challenge post-dialysis weight as the initial step in attaining the assigned target SBP, the intensive SBP goal was achieved by use of additional antihypertensive medications. Target weights actually increased in the intervention group, suggesting inadequate management of the extracellular volume status.
No population-specific evidence has established BP thresholds and targets for interdialytic BP (i.e., not pre-or post-dialysis) for the dialysis population. Extrapolating from current general population hypertension guidelines may be reasonable, but such guidelines do not account for differences in cardiovascular risk in dialysis patients. Specifically, numerous observational studies [bib_ref] Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves..., Foley [/bib_ref] [bib_ref] Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis..., Robinson [/bib_ref] [bib_ref] The optimal blood pressure target in different dialysis populations, Jhee [/bib_ref] and the Blood-Pressure-in-Dialysis study [bib_ref] BP in dialysis: results of a pilot study, Miskulin [/bib_ref] have suggested harm from lower BPs. Targeting too low of a threshold may heighten cardiovascular risk in some patients. The 2017 American College of Cardiology/American Heart Association Guidelines 29 BP threshold and target is 130/80 mm Hg; in contrast, the 2018 European Society of Hypertension/European Society of Cardiology Guidelines 30 recommend an SBP target of <130 mm Hg for ages <65 years, and an SBP target range of 130-140 mm Hg for all others. Based on existing evidence, definitive recommendations regarding BP treatment targets cannot be made. An individualized approach is a priori necessary for all patients receiving dialysis, with a particular focus on avoiding overly low BPs, and special consideration regarding intradialytic and interdialytic BP patterns, volume management, and ccomorbidities.

## Definitions of intradialytic hypotension and hypertension
In a typical dialysis treatment session, BP decreases from preto post-dialysis; the magnitude of this reduction most closely relates to the magnitude of UF. [bib_ref] Hypertension in dialysis patients: a consensus document by the European Renal and..., Sarafidis [/bib_ref] Intradialytic hypotension is a serious complication of HD, associated with vascular access thrombosis, inadequate dialysis dose, and mortality. [bib_ref] Association of mortality risk with various definitions of intradialytic hypotension, Flythe [/bib_ref] [bib_ref] Intradialytic hypotension and vascular access thrombosis, Chang [/bib_ref] [bib_ref] Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis..., Shoji [/bib_ref] Intradialytic hypotension prevalence ranges from 15% to 50% of HD treatments, depending on the definition [fig_ref] Table 2 |: Definitions of intradialytic hypotension and intradialytic hypertension [/fig_ref].
Any symptomatic decrease in BP or a nadir intradialytic SBP of <90 mm Hg should prompt reassessment of BP management. This reassessment includes, but is not limited to, UF rate, dialysis treatment time, interdialytic weight gain (IDWG), dry-weight estimation, and antihypertensive medication use, in concordance with discussions in the following sections. Avoidance of intradialytic hypotension should not come at the expense of maintaining euvolemia or ensuring adequate dialysis time. Data on intradialytic hypotension during home HD or intermittent PD techniques are scarce.
Intradialytic hypertension is the phenomenon of BP increase during or immediately after a dialysis session, and it involves activation of the sympathetic nervous and renin-angiotensin systems, endothelial stiffness, volume excess, and other mechanisms. [bib_ref] Intradialytic hypertension: a less-recognized cardiovascular complication of hemodialysis, Inrig [/bib_ref] [bib_ref] Intradialysis hypertension in end-stage renal disease patients: clinical epidemiology, pathogenesis, and treatment, Georgianos [/bib_ref] Intradialytic hypertension has an estimated prevalence of 5%-15%, depending on the definition used [fig_ref] Table 2 |: Definitions of intradialytic hypotension and intradialytic hypertension [/fig_ref]. Defining it as an SBP increase of >10 mm Hg from pre-to post-dialysis accurately identifies persons with persistently elevated interdialytic BP [bib_ref] A comparative study of short-term blood pressure variability in hemodialysis patients with..., Bikos [/bib_ref] and demonstrates an association with hospitalization and mortality. [bib_ref] Decreased pulse pressure during hemodialysis is associated with improved 6-month outcomes, Inrig [/bib_ref] [bib_ref] Association of blood pressure increases during hemodialysis with 2-year mortality in incident..., Inrig [/bib_ref] An SBP increase of >10 mm Hg from pre-to post-dialysis into the hypertensive range in at least 4 of 6 consecutive dialysis treatments should prompt a more extensive evaluation of BP and volume management, including out-of-unit BP measurements and a critical assessment of dry weight. Currently, there are no data on intradialytic hypertension in home HD or PD.

## Bp variability
Fluctuations of BP over the very short-term (beat-by-beat), short-term (within 24 hours), mid-term (day-by-day), and long-term (visit-to-visit) are associated with target-organ damage, cardiovascular events, and mortality in patients on HD. [bib_ref] The association of interdialytic blood pressure variability with cardiovascular events and all-cause..., Sarafidis [/bib_ref] [bib_ref] Association of intradialytic blood pressure variability with increased all-cause and cardiovascular mortality..., Flythe [/bib_ref] [bib_ref] Visit-to-visit blood pressure variability is a strong predictor of cardiovascular events in..., Rossignol [/bib_ref] [bib_ref] Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis, Chang [/bib_ref] However, whether BP variability is a modifiable risk factor or a marker of underlying pathology (e.g., volume shifts, arterial stiffness) remains uncertain. There are no studies of interventions targeting BP variability, so no treatment recommendations can be made, and further research is needed .

## Pharmacologic approaches to suboptimal bp and volume control
Use of antihypertensive medications.-Deciding when to use antihypertensive medications requires consideration of indication (e.g., BP lowering alone or cardioprotection). In the first case, nonpharmacologic treatments should be considered first, as volume overload underlies most cases of BP elevation in dialysis. [bib_ref] Assessment and management of hypertension in patients on dialysis, Agarwal [/bib_ref] [bib_ref] Hypertension in dialysis patients: a consensus document by the European Renal and..., Sarafidis [/bib_ref] [bib_ref] The clinical problems of hypertension treatment in hemodialysis patients, Loutradis [/bib_ref] [bib_ref] Antihypertensive medication use in older patients transitioning from chronic kidney disease to..., Chang [/bib_ref] If BP remains above target after nonpharmacologic measures directed at volume control, then initiation or up-titration of antihypertensive medications is necessary. If BP is well controlled and antihypertensive medications interfere with UF, reducing medications to allow for enhanced UF is reasonable. When antihypertensive medications are already being used for BP control and cardioprotection, it is reasonable to continue them unless they interfere with targeting euvolemia.
Choice of antihypertensive medications.-Patient heterogeneity and scarcity of comparative evidence preclude recommending any one medication class over another for all patients. Antihypertensive medications considered first-line in the general population (e.g., angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and calcium channel blockers) can also be considered first-line to lower BP in patients receiving dialysis. It is reasonable to choose medications based on patient characteristics, cardiovascular indications, and availability [fig_ref] Table 3 |: Medication classes for blood pressure management in dialysis blocker atenolol compared to... [/fig_ref].
Pharmacokinetics and dialyzability are also important considerations. For example, one retrospective study found that nondialyzable -blockers (e.g., propranolol) but not highly dialyzable -blockers (e.g., atenolol, metoprolol) are associated with lower mortality risk, possibly due to preserved intradialytic protection against arrhythmias. [bib_ref] Beta-blocker dialyzability and mortality in older patients receiving hemodialysis, Weir [/bib_ref] In contrast, another retrospective study showed higher mortality rates with the nondialyzable carvedilol versus the highly dialyzable metoprolol, which was attributed to a higher likelihood of intradialytic hypotension with carvedilol. [bib_ref] A comparative study of carvedilol versus metoprolol initiation and 1-year mortality among..., Assimon [/bib_ref] Additionally, the data assessing drug dialyzability contain uncertainties. For example, a recent study suggests that bisoprolol may in fact be dialyzable, contrary to what had been previously thought. [bib_ref] Beta-blocker dialyzability in maintenance hemodialysis patients: A randomized clinical trial, Tieu [/bib_ref] It is reasonable to consider intradialytic BP patterns with regard to drug dialyzability, and it may be prudent to avoid nondialyzable medications in the setting of frequent intradialytic hypotension. For relatively stable intradialytic BP, use of longer-acting, once-daily medication may improve adherence and reduce pill burden.
The timing of antihypertensive medication administration should be individualized, taking into account interdialytic BP and the frequency of intradialytic hypotension. The effectiveness of withholding antihypertensive agents before dialysis in reducing intradialytic hypotension is unknown [bib_ref] Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension, Davenport [/bib_ref] and is being investigated in an ongoing RCT (NCT03327909). [bib_ref] Antihypertensive medication withholding practices in hemodialysis: a survey study of patients and..., Haase [/bib_ref] Medications to raise BP in intradialytic hypotension.-Nonmedication strategies for treating intradialytic hypotension, such as cardiovascular status optimization, UF rate minimization, and target-weight reassessment, should be prioritized. Medication options include midodrine, [bib_ref] Impact of drugs on intradialytic hypotension: antihypertensives and vasoconstrictors, Chang [/bib_ref] argi-nine-vasopressin, 72-76 sertraline, 77,78 droxidopa, amezinium metilsulfate, [bib_ref] Antihypotensive and hormonal effects of amezinium metilsulfate in hypotensive hemodialysis patients, Watari [/bib_ref] fludrocortisone, and carnitine. [bib_ref] Impact of drugs on intradialytic hypotension: antihypertensives and vasoconstrictors, Chang [/bib_ref] In general, the evidence base for these strategies is relatively weak, with most studies being small and of short duration. [bib_ref] Impact of drugs on intradialytic hypotension: antihypertensives and vasoconstrictors, Chang [/bib_ref] The most widely used is midodrine, an oral vasoconstrictor, although efficacy data are limited, [bib_ref] The impact of midodrine on outcomes in patients with intradialytic hypotension, Brunelli [/bib_ref] as is its availability outside the US [fig_ref] Table 3 |: Medication classes for blood pressure management in dialysis blocker atenolol compared to... [/fig_ref].

## The dialysis prescription as it relates to bp and volume target weight
A critical element of the dialysis prescription is the target weight; a target weight that is too low may lead to hypotension and faster loss of RKF, whereas a weight that is too high results in hypervolemia . The result is a narrow therapeutic window in which to avoid acute and chronic complications of volume depletion and overload. Target weight differs in concept and in practice from the estimated dry weight, as target weight can vary from treatment to treatment. In some cases (e.g., acute illness, severe symptoms), it may be appropriate to maintain an individual slightly above the estimated dry weight; however, the long-term risks from chronic volume overload in this setting must be weighed carefully. 80

## Intradialytic hypotension and the hd prescription
Major contributors to intradialytic hypotension are insufficient intravascular volume to support the desired UF rate, and inadequate cardiovascular compensatory responses. The UF rate is a function of dialysis treatment time and volume removal. [bib_ref] Fluid first or not so fast: ultrafiltration rate and the ESRD Quality..., Weiner [/bib_ref] In observational data, higher UF rates, even as low as 6 ml/h per kg, are associated with higher mortality risk. [bib_ref] Ultrafiltration rate and mortality in maintenance hemodialysis patients, Assimon [/bib_ref] [bib_ref] Rapid fluid removal during dialysis is associated with cardiovascular morbidity and mortality, Flythe [/bib_ref] Although no RCTs have demonstrated that lowering UF rates improves outcomes, biologic plausibility data support a relationship between higher UF rates and end-organ ischemia (heart, brain, liver, gut, kidneys). [bib_ref] Hemodialysis-induced cardiac injury: determinants and associated outcomes, Burton [/bib_ref] [bib_ref] Dying to feel better: the central role of dialysis-induced tissue hypoxia, Mcintyre [/bib_ref] [bib_ref] Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in..., Mcintyre [/bib_ref] [bib_ref] Hepato-splanchnic circulatory stress: an important effect of hemodialysis, Grant [/bib_ref] [bib_ref] Randomized clinical trial of dialysate cooling and effects on brain white matter, Eldehni [/bib_ref] [bib_ref] Intradialytic cardiac magnetic resonance imaging to assess cardiovascular responses in a short-term..., Buchanan [/bib_ref] [bib_ref] Renal perfusion during hemodialysis: Intradialytic blood flow decline and effects of dialysate..., Marants [/bib_ref] A critical unanswered question is how to balance the potential risks from higher UF rates with the potential risks from volume overload. [bib_ref] Target weight achievement and ultrafiltration rate thresholds: potential patient implications, Flythe [/bib_ref] In the absence of conclusive data, using one specific UF rate threshold for all patients at all times is likely inappropriate. Instead, clinicians should consider a range of factors, including intradialytic hemodynamics, comorbid medical conditions, symptoms, current conditions, and other factors as a means to weigh the potential harms of higher UF rates against their potential benefits. Decisions may differ on a treatment-to-treatment basis.
Although questions about how to individualize UF rate prescriptions remain, patient and clinician awareness and frequent consideration of the UF rate are critically important to BPand volume-related decisions. UF rates can be lowered by increasing HD time and/or decreasing IDWG . Increased UF time can be accomplished by lengthening or adding treatments. Patient preference and local logistics and resources are important considerations.
Strategies aimed at improving vascular compensation and/ or tolerance of UF may also lower the risk of UF-induced intradialytic hypotension and are listed in [fig_ref] Table 5 |: Hemodialysate composition and blood pressure and volume status Further research needed regarding... [/fig_ref]. Altering dialysate sodium concentration is the most debated approach [fig_ref] Table 5 |: Hemodialysate composition and blood pressure and volume status Further research needed regarding... [/fig_ref]. Prospective studies suggest that use of lower dialysate sodium is associated with lower IDWG and BP [bib_ref] Effect of lowering dialysate sodium concentration on interdialytic weight gain and blood..., Mendoza [/bib_ref] [bib_ref] High versus low dialysate sodium concentration in chronic haemodialysis patients: a systematic..., Basile [/bib_ref] but also show an association with intradialytic hypotension and symptoms, including cramps. [bib_ref] Low dialysate sodium levels for chronic haemodialysis, Dunlop [/bib_ref] Observational studies have yielded mixed results regarding the association of dialysate sodium and mortality. [bib_ref] Dialysate sodium concentration and the association with interdialytic weight gain, hospitalization, and..., Hecking [/bib_ref] [bib_ref] Predialysis serum sodium level, dialysate sodium, and mortality in maintenance hemodialysis patients:..., Hecking [/bib_ref] [bib_ref] Dialysate sodium, serum sodium and mortality in maintenance hemodialysis, Mc Causland [/bib_ref] The Sodium Lowering in Dialysate (SoLID) RCT [bib_ref] Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a..., Dunlop [/bib_ref] [bib_ref] Update: rationale and design of the Sodium Lowering In Dialysate (SoLID) trial:..., Dunlop [/bib_ref] assesses the effects of low versus standard dialysate sodium concentration on regression of left ventricular mass, with results pending. Therefore, the ideal dialysate sodium concentration remains uncertain. A large multinational, pragmatic trial is ongoing (RESOLVE, NCT02823821). Moreover, the prescribed and delivered dialysate sodium concentrations can differ, rendering individualization of prescriptions challenging and potentially unsafe. [bib_ref] Comparison of prescribed and measured dialysate sodium: a quality improvement project, Gul [/bib_ref] In general, sodium balance should be negative during an HD treatment, 1 given the tension between enhanced vascular space viability during a single treatment and lower IDWG across many treatments.
Additional questions include whether there is a role for UF profiling or isolated UF followed by HD (i.e., sequential dialysis) and how to address logistic issues such as the 3-day gap in some regions and limited access to thrice-weekly HD in resource-poor settings.

## Chronic hypotension and the hd prescription
Chronically hypotensive patients are a particularly challenging group to manage. For many of these individuals, the same principles hold, most notably increasing dialysis time. Patients with chronic hypotension may tolerate PD better than HD, yet further study is required to confirm whether outcomes are better after a transition in modalities.

## Hypotension and the pd prescription
Conditions associated with hypotension in PD include aggressive UF and/or failure to adjust PD prescription with decreased dietary intake or hypovolemia; failure to adjust antihypertensive medications; overly stringent salt restriction; and low cardiac output. Strategies to prevent hypotension include reducing UF volume by adjusting solutions (e.g., using less hypertonic glucose solutions or changing icodextrin to conventional 1.5% glucose solution); omitting day dwell (in automated PD [APD]) or night dwell (in continuous ambulatory PD) in those with significant RKF without compromising clearance; withholding antihypertensive medications; and liberalizing salt intake.

## Hypertension and the hd prescription
Dialytic management of hypertension in patients receiving HD begins with addressing volume overload. Options include gently probing the prescribed target weight, [bib_ref] Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial, Agarwal [/bib_ref] increasing treatment time and/or frequency (possibly through home HD or center-based nocturnal HD), decreasing IDWG, and improving vascular stability during HD .

## Hypertension and the pd prescription
As among HD patients, volume is a significant contributor to hypertension among PD patients. The principle behind preventing or treating hypertension in PD is to maximize peritoneal UF and urine output to achieve euvolemia with a prescription that has the lowest glucose load to patients and without jeopardizing RKF. Strategies to maximize UF for the long dwell include shortening the dwell with glucose-based solutions (high transporter), using higher tonicity glucose-based solutions (but this is less preferable), using icodextrin for long day dwell for APD or long overnight dwell for continuous ambulatory PD, restricting dietary salt, and in those with RKF, using diuretics to increase urine volume . 55,100 Experimental approaches include using a low-sodium dialysate, 101 a bimodal solution with glucose and icodextrin, [bib_ref] A combined crystalloid and colloid Pd solution as a glucosesparing strategy for..., Freida [/bib_ref] 2 icodextrin exchanges per day, [bib_ref] Effects of twice-daily icodextrin administration on blood pressure and left ventricular mass..., Sav [/bib_ref] and incorporating intermittent hybrid therapy, all of which require further evaluation.
Assessment of membrane function may be considered as adjunctive to clinical measures of UF volume. The peritoneal equilibration test is used in solute removal modelling prediction software. However, this test alone should not guide PD prescriptions. The correlation between solute transport characteristics and UF capacity is poor. The test may be useful in identifying true membrane failure versus other causes of impaired UF and volume excess (such as mechanical causes or excess intake). [bib_ref] Analysis of ultrafiltration failure in peritoneal dialysis patients by means of standard..., Ho-Dac-Pannekeet [/bib_ref] No robust data suggest that continuous ambulatory PD or APD results in superior volume control relative to the other. [bib_ref] Comparative outcomes between continuous ambulatory and automated peritoneal dialysis: a narrative review, Bieber [/bib_ref] Therefore, PD modality selection considerations should go beyond BP and volume control, centering on broader concerns, such as patient preferences and local resources. APD has a potential for greater UF than continuous ambulatory PD, and mostly observational data suggest that APD may have a greater benefit for rapid transporters. [bib_ref] Comparative outcomes between continuous ambulatory and automated peritoneal dialysis: a narrative review, Bieber [/bib_ref] Changing the PD solution type, exchange number, and dwell time are important PD prescription strategies to optimize BP and volume management.
Compared with standard glucose solutions, the more biocompatible, neutral pH, or low glucose degradation products solutions may prolong the time to anuria when used for more than 12 months, and this may indirectly benefit volume control. [bib_ref] Biocompatible dialysis fluids for peritoneal dialysis, Htay [/bib_ref] [bib_ref] Effects of biocompatible versus standard fluid on peritoneal dialysis outcomes, Johnson [/bib_ref] The more biocompatible PD solutions have also been associated with stable peritoneal membrane function and UF capacity over time, compared with conventional glucose-based solutions, which have been associated with a progressive decline in UF capacity over time. [bib_ref] The effect of low glucose degradation product, neutral pH versus standard peritoneal..., Johnson [/bib_ref] [bib_ref] Biocompatible solutions and long-term changes in peritoneal solute transport, Elphick [/bib_ref] [bib_ref] Effects of long-term treatment with low-GDP, pH-neutral solutions on peritoneal membranes in..., Tawada [/bib_ref] Icodextrin.-Moderate-certainty evidence indicates that icodextrin augments peritoneal UF compared with standard glucose solutions. [bib_ref] Biocompatible dialysis fluids for peritoneal dialysis, Htay [/bib_ref] Three RCTs have examined the effect of icodextrin in high or high-average transporters [bib_ref] Icodextrin improves the fluid status of peritoneal dialysis patients: results of a..., Davies [/bib_ref] [bib_ref] Superiority of icodextrin compared with 4.25% dextrose for peritoneal ultrafiltration, Finkelstein [/bib_ref] [bib_ref] Echocardiographic, electrocardiographic and blood pressure changes induced by icodextrin solution in diabetic..., Paniagua [/bib_ref] ; in general, higher transporters derived greater UF benefit from icodextrin. [bib_ref] Hemodynamic effects of peritoneal dialysis solutions on the rat peritoneal membrane: role..., Mortier [/bib_ref] and clinical data [bib_ref] Peritoneal glucose exposure and changes in membrane solute transport with time on..., Davies [/bib_ref] suggest that hypertonic glucose solutions are deleterious to peritoneal health and may cause adverse metabolic effects. [bib_ref] Hemodynamic effects of peritoneal dialysis solutions on the rat peritoneal membrane: role..., Mortier [/bib_ref] [bib_ref] Peritoneal glucose exposure and changes in membrane solute transport with time on..., Davies [/bib_ref] [bib_ref] ISPD Cardiovascular and Metabolic Guidelines in Adult Peritoneal Dialysis Patients Part I-Assessment..., Wang [/bib_ref] Frequent use of 4.25% solutions should prompt evaluation of dietary salt and fluid intake, PD prescription, mechanical problems, and peritoneal membrane failure.

## 4.25% pd solutions.-animal

## Preserving residual kidney function
In observational PD [bib_ref] Relative contribution of residual renal function and peritoneal clearance to adequacy of..., Bargman [/bib_ref] [bib_ref] The importance of residual renal function in dialysis patients, Wang [/bib_ref] and HD 119 studies, better-preserved RKF is associated with better survival rates and patient outcomes. Preserving RKF allows the incorporation of diuretics into regimens to help reduce IDWG. In addition, RKF preservation allows consideration of incremental PD prescriptions that reduce treatment burden. Likewise, the presence of significant RKF is an important consideration in incremental HD, [bib_ref] Hemodialysis prescription for incident patients: Twice seems nice, but is it incremental?, Toth-Manikowski [/bib_ref] although the purported benefits are untested by adequately powered RCTs. What the optimal approach is for measuring RKF is controversial. [bib_ref] Development and validation of residual kidney function estimating equations in dialysis patients, Steubl [/bib_ref] In many cases, urine volume measurement or potentially patient-reported urine volume 123 may be adequate. RCT data on RKF preservation strategies beyond the common-sense strategies of hypotension and nephrotoxin avoidance are limited [fig_ref] Table 6 |: Residual kidney functionWhen to assess124 Limited consensus about frequency, which ranges from... [/fig_ref]. Moreover, the cardioprotective strategies of more intensive volume control and more frequent HD may hasten RKF loss. [bib_ref] Effect of frequent hemodialysis on residual kidney function, Daugirdas [/bib_ref] Thus, individualized approaches are necessary.

## Extracellular volume management and technologies
RELEVANT TO VOLUME MANAGEMENT

## Measuring extracellular volume
There are no widely available, precise methods for measuring extracellular volume. Evaluation of any approach to measuring volume is complicated by the absence of an accessible gold standard. In most instances, volume assessment relies on clinical markers, including patient history and physical examination. Volume assessment includes examining trends in weights, BPs, and signs and symptoms. The physical examination is the mainstay of volume assessment, but data suggest that BP, jugular vein distension, and edema may not correlate well with volume status. [bib_ref] On the importance of pedal edema in hemodialysis patients, Agarwal [/bib_ref] [bib_ref] Can the clinical examination diagnose left-sided heart failure in adults?, Badgett [/bib_ref] [bib_ref] The rational clinical examination. Is this patient hypovolemic?, Mcgee [/bib_ref] Despite these limitations, a physical examination should include evaluation for the presence of edema, degree of filling of the jugular vein, and lung auscultation. Physical examination paired with review of longitudinal weights, BPs, and symptoms should be performed at least once per month, with the optimal frequency individualized based on patient circumstances.
Other tools for evaluating extracellular volume are listed in [fig_ref] Table 7 |: Volume-assessment parameters and tools Data supporting associations between physical signs and volume... [/fig_ref]. Major challenges are limited availability and the lack of evidence-based protocols. Certain tools, such as bioimpedance spectroscopy and lung ultrasound, can be used to confirm clinical suspicion of extracellular excess and are of prognostic value. [bib_ref] The role of bioimpedance and biomarkers in helping to aid clinical decision-making..., Davies [/bib_ref] [bib_ref] Predicting mortality in haemodialysis patients: a comparison between lung ultrasonography, bioimpedance data..., Siriopol [/bib_ref] [bib_ref] Effective and timely evaluation of pulmonary congestion: qualitative comparison between lung ultrasound..., Donadio [/bib_ref] [bib_ref] Lung ultrasound during hemodialysis: the role in the assessment of volume status, Vitturi [/bib_ref] The use of bioimpedance to guide target weight estimation may improve BP and left ventricular mass. [bib_ref] Effect of fluid management guided by bioimpedance spectroscopy on cardiovascular parameters in..., Hur [/bib_ref] Data on the effectiveness of bioimpedance-guided volume management on symptoms and hospitalizations are mixed. [bib_ref] The role of bioimpedance and biomarkers in helping to aid clinical decision-making..., Davies [/bib_ref] [bib_ref] Bioimpedance-guided fluid management in hemodialysis patients, Moissl [/bib_ref] [bib_ref] Fluid management in haemodialysis: Conventional versus body composition monitoring (BCM) supported management..., Ponce [/bib_ref] Lung ultrasound-guided volume management improves BP control, [bib_ref] The effect of dry-weight reduction guided by lung ultrasound on ambulatory blood..., Loutradis [/bib_ref] and an ongoing trial of lung ultrasound-guided treatment and cardiovascular outcomes is underway (LUST Study, NCT02310061). The biggest barriers to using these technologies are cost (of the test itself and time to administer it) and availability.
In resource-constrained environments, clinical examination remains the mainstay of volume assessment.

## Technical intradialytic strategies for managing bp and volume
Temperature biofeedback.-Cooling the dialysate temperature through various methods (e.g., lowering temperature relative to measured body temperature or lowering temperature to a set threshold-35 C or 36 C-irrespective of body temperature) has been associated with hemodynamic stability, [bib_ref] Cool dialysate reduces asymptomatic intradialytic hypotension and increases baroreflex variability, Chesterton [/bib_ref] [bib_ref] Randomized controlled trial of individualized dialysate cooling for cardiac protection in hemodialysis..., Odudu [/bib_ref] [bib_ref] A systematic review of the clinical effects of reducing dialysate fluid temperature, Selby [/bib_ref] [bib_ref] Associations between hemodialysis facility practices to manage fluid volume and intradialytic hypotension..., Dasgupta [/bib_ref] and lowering temperature to 0.5 C below body temperature is well tolerated by most patients. An ongoing trial (MY TEMP, NCT02628366) is evaluating the effect of dialysate cooling on cardiovascular events.
Blood volume monitoring.-Evidence is conflicting regarding whether relative blood volume monitoring can predict intradialytic hypotension [bib_ref] Randomized crossover trial of blood volume monitoringguided ultrafiltration biofeedback to reduce intradialytic..., Leung [/bib_ref] [bib_ref] Relative plasma volume monitoring during hemodialysis AIDS the assessment of dry weight, Sinha [/bib_ref] [bib_ref] Linear decay of relative blood volume during ultrafiltration predicts hemodynamic instability, Mitra [/bib_ref] [bib_ref] Do changes in relative blood volume monitoring correlate to hemodialysis-associated hypotension?, Booth [/bib_ref] ; however, evidence suggests that relative blood volume monitoring is of prognostic value. [bib_ref] All-cause mortality in relation to changes in relative blood volume during hemodialysis, Preciado [/bib_ref] In the randomized Crit-Line Intradialytic Monitoring Benefit (CLIMB) trial, mortality and hospitalization rates were higher among patients undergoing intradialytic blood volume monitoring versus conventional clinical monitoring. However, the interpretation of the trial is limited by the atypically low hospitalization and mortality rates and questions regarding study protocol adherence. [bib_ref] Intradialytic blood volume monitoring in ambulatory hemodialysis patients: a randomized trial, Reddan [/bib_ref] [bib_ref] Why assistive technology is needed for probing of dry weight, Sinha [/bib_ref] In children, although there are no RCT data, evidence indicates that a relative blood volume-guided UF algorithm improves BP control. [bib_ref] A standard, noninvasive monitoring of hematocrit algorithm improves blood pressure control in..., Patel [/bib_ref] UF profiling.-RCT data on UF profiling, independent of relative blood volume monitoring and sodium profiling, are scarce, with a crossover RCT published in 2000 demonstrating no benefit. [bib_ref] Ultrafiltration profiling and measurement of relative blood volume as strategies to reduce..., Donauer [/bib_ref] Isolated UF.-Isolated UF is commonly used, 147 but currently there is limited evidence to support this approach.
Sodium profiling.-Although data to support sodium profiling are scant, one metaanalysis suggests that stepwise versus linear sodium profiling is associated with greater hemodynamic stability.Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) suggest that the routine use of sodium modelling/profiling to limit or prevent intradialytic hypotension is associated with increased all-cause mortality. [bib_ref] Associations between hemodialysis facility practices to manage fluid volume and intradialytic hypotension..., Dasgupta [/bib_ref] Sodium profiling must be used judiciously, as it may result in sodium loading and hypervolemia.
Bioimpedance.-Data from a study of 15 patients indicate that bioimpedance may have a role for assessing the relationship between plasma refilling and tissue hydration during dialysis, [bib_ref] Slope analysis of blood volume and calf bioimpedance monitoring in hemodialysis patients, Seibert [/bib_ref] but evidence is currently insufficient to justify routine use for intradialytic volume management. As reported above, bioimpedance may have a role in extracellular volume management.
Hemodiafiltration.-Convective therapies such as hemodiafiltration may have a role in preventing intradialytic hypotension. An RCT including 146 patients demonstrated a significant reduction in intradialytic hypotension in the hemodiafiltration group compared with regular HD, [bib_ref] Hemofiltration and hemodiafiltration reduce intradialytic hypotension in ESRD, Locatelli [/bib_ref] and others have demonstrated better hemodynamic stability with increasing convection volume prescriptions. [bib_ref] Association of intradialytic hypotension and convective volume in hemodiafiltration: results from a..., Mora-Bravo [/bib_ref] Further research is needed.

## Remote monitoring and wearable health technologies
For home-based dialysis, older technologies, such as telephone calls, remain important. However, systems are advancing, and many modern dialysis machines can transmit data, such as BP, weight, oxygen saturation, and UF rate, back to central locations. None of these tools has been proven to enhance outcomes, but more investigation is needed. Wearable devices, including dialysis apparatuses and cardiac tools for measuring volume status, heart rhythm, and other factors, are currently in development. Their roles in dialysis management remain nascent. These tools have the potential to improve patient autonomy and risk-factor management but will need to be aligned with local health and payment systems to realize widespread uptake.

## Volume-related patient experiences and nonpharmacologic

## Interventions for suboptimal bp and volume control

## Signs and symptoms of volume overload or depletion
Various signs and symptoms are associated with volume overload or depletion: breathlessness, orthopnea, edema, elevated jugular venous pressure, cardiomegaly, lung congestion, light-headedness, cramps, erectile dysfunction, thirst, and weight gain and loss, among others. Small studies suggest that better BP and volume management may improve symptoms. [bib_ref] Treating hypertension in hemodialysis improves symptoms seemingly unrelated to volume excess, Agarwal [/bib_ref] Some dialysis patients have symptom clusters that relate to volume status, and it is helpful for both clinicians and patients to recognize these individualized indicators.
Research aimed at understanding symptom constellations is needed. 162

## Incorporating volume-related symptoms into dialysis prescription decision-making
National guidelines suggest UF rate thresholds and dietary restrictions, [bib_ref] Assessment and management of hypertension in patients on dialysis, Agarwal [/bib_ref] [bib_ref] Hypertension in dialysis patients: a consensus document by the European Renal and..., Sarafidis [/bib_ref] [bib_ref] Japanese society for dialysis therapy clinical guideline for "Maintenance hemodialysis: hemodialysis prescriptions, Watanabe [/bib_ref] but none address the relationship between volume status and symptoms. In consensus-building exercises, patients prioritize symptoms that plausibly relate to volume, such as fatigue and cramping, for treatment and new research. [bib_ref] Developing a set of core outcomes for trials in hemodialysis: an international..., Evangelidis [/bib_ref] [bib_ref] Symptom prioritization among adults receiving in-center hemodialysis: a mixed methods study, Flythe [/bib_ref] Symptoms, especially when new or escalating, should trigger review of volume-related aspects of the dialysis prescription. However, symptoms are seldom formally assessed on a frequent basis, and patients describe under-reporting their symptoms. [bib_ref] Perspectives on symptom experiences and symptom reporting among individuals on hemodialysis, Flythe [/bib_ref] Patients should be engaged, educated, and encouraged to report symptoms routinely. [bib_ref] Perspectives on symptom experiences and symptom reporting among individuals on hemodialysis, Flythe [/bib_ref] Symptom assessment surveys have been developed for dialysis patients, [bib_ref] Development of a symptom assessment instrument for chronic hemodialysis patients: the Dialysis..., Weisbord [/bib_ref] but most instruments assess symptoms over 1 to 4 weeks, obscuring links between symptoms and the dialysis prescription. Ideally, a symptom measurement tool would capture relevant symptoms and their severity in real time, without being burdensome to patients.
Incorporating symptoms into dialysis prescription considerations may focus discussions on aspects of care that are most important to patients. In considering symptoms, risk-versusbenefit tradeoffs must be carefully explained and weighed. Good communication, both among the dialysis team members and between the team and the patient, is essential to ensure that changes in target weight (or other prescription aspects) are carefully monitored. Inclusion of patient experience and well-being in benchmarking could help align the goals of patients and providers.

## Salt and fluid restrictions for bp and volume control
Salt and fluid restrictions are the cornerstone nonpharmacologic strategies for BP and volume management; however, data supporting their effectiveness are surprisingly scant. A systematic review evaluated 16 studies of psychological interventions for addressing nonadherence to fluid restrictions in HD patients, [bib_ref] A systematic review of psychological interventions for the treatment of nonadherence to..., Sharp [/bib_ref] including behavior modification, cognitive therapy, social reinforcement, and stress management. At best, these studies indicated only a modest postintervention decrease in IDWG. However, small studies have shown that restricting salt intake can reduce IDWG in patients receiving HD, [bib_ref] The benefit of salt restriction in the treatment of end-stage renal disease..., Kayikcioglu [/bib_ref] and BP in patients receiving PD. [bib_ref] The effect of dietary salt restriction on hypertension in peritoneal dialysis patients, Inal [/bib_ref] Although the serum sodium level that triggers thirst varies across individuals,most patients maintain their pre-dialysis sodium levels within the normal range. This finding suggests that water intake is adjusted to match salt intake, underscoring the importance of emphasizing salt restriction, rather than the overly simplistic advice to just restrict fluid intake. For patients with low pre-dialysis sodium level, other issues should be considered, such as poorly controlled glucose levels or excessive drinking. Dietary restrictions and nutritional status.-Dietary interventions to reduce IDWG must be made cautiously so as not to compromise nutritional status. Such caution is particularly important in frail patients, who may tolerate UF poorly even when hypervolemic. In growing children, it is important to monitor volume status and body composition regularly to ensure that the target weight is adjusted to match growth. If fluid gains between treatments persist despite dietary changes, an augmented dialysis regimen should be considered. Goals of care should be reviewed frequently.

## Effects of dietary restrictions on

## Exercise for bp and volume control
Although there are few studies of exercise and volume, 174 combined aerobic and resistance training has been associated with SBP and diastolic BP reductions. [bib_ref] Combined training is the most effective training modality to improve aerobic capacity..., Scapini [/bib_ref] Although many dialysis patients want to exercise, [bib_ref] Benefits and barriers to and desired outcomes with exercise in patients with..., Moorman [/bib_ref] barriers to exercise of any type include fatigue, dialysis access, time constraints, comorbidities, fear, and (for intradialytic exercise) clinic personnel workload. 177,178

# Conclusion
Managing BP and volume in dialysis requires an individualized approach with integration of numerous clinical, dialysis treatment, and patient factors. Bolstered by shared commitments to improving volume management and focusing on patient-stated priorities, the conference participants identified numerous strategies and technologies that should be considered in the design and implementation of future RCTs in this critical, yet understudied area. APD, automated peritoneal dialysis; BMI, body mass index; CAPD, continuous ambulatory peritoneal dialysis; GDP, glucose degradation product; HD, hemodialysis; HDF, hemodiafiltration; IDWG, interdialytic weight gain; PD, peritoneal dialysis; RKF, residual kidney function; UF, ultrafiltration. Included studies were all of short duration and had small sample sizes , and none examined clinical endpoints such as death or cardiovascular events.
[fig] Figure 1 |: Tension in balancing volume status within a narrow therapeutic window. . Author manuscript; available in PMC 2021 May 01. [/fig]
[fig] Figure 2 |Figure 3 |: Contributors to and consequences of blood pressure and volume abnormalities in dialysis.GI, gastrointestinal; HD, hemodialysis; IDWG, interdialytic weight gain; PD, peritoneal dialysis; UF, ultrafiltration. . Author manuscript; available in PMC 2021 May 01. . Conceptual framework for individualizing dialysis prescriptions. [/fig]
[table] Table 2 |: Definitions of intradialytic hypotension and intradialytic hypertension [/table]
[table] Table 3 |: Medication classes for blood pressure management in dialysis blocker atenolol compared to the ACEi lisinopril in HD patients with hypertension and left ventricular hypertrophy 52 RCT: Lower risk of death and cardiovascular death with carvedilol versus placebo in HD patients with dilated cardiomyopathy who were also receiving digoxin and ACEi or ARB53 Continuation of loop diuretics after HD initiation is associated with lower IDWG and lower intradialytic hypotension and hospitalization rates58 Mineralocorticoid receptor antagonists RCT: Some trials in patients on dialysis have shown benefit on cardiovascular outcomes with spironolactone vs. pla-cebo,[59][60][61] whereas others have not 62Ongoing RCTs: spironolactone and cardiovascular outcomes in HD patients (ACHIEVE and ALCHEMIST) 63Hypotension Midodrine Meta-analysis: Nadir SBP improved by an average of 13 mm Hg (95% CI: 9-18 mm Hg, P < 0.0001), and 6 of the 10 studies reported an improvement in symptoms associated with intradialytic hypotension with use of midodrine vs. control.64 [/table]
[table]  Observational: Matched midodrine users to non-users (including matching by mean peridialytic BP level) found that midodrine use was associated with significantly higher risks of cardiovascular events, all-cause hospitalization, and mortality.65 ACEi, angiotensin-converting enzyme inhibitor; ACHIEVE, Aldosterone Blockade for Health Improvement Evaluation in End-stage Renal Disease; ALCHEMIST, ALdosterone Antagonist Chronic HEModialysis; ARB, angiotensin receptor blocker; BP, blood pressure; CI, confidence interval; HD, hemodialysis; IDWG, interdialytic weight gain; PD, peritoneal dialysis; RCT, randomized controlled trial; SBP, systolic blood pressure.Kidney Int. Author manuscript; available in PMC 2021 May 01. Nonpharmacologic interventions to prevent intradialytic hypotension Facility logistics; patient preference; infeasible in resource-poor regions Increase frequency of dialysis treatments Facility logistics; patient preference; infeasible in resource-poor regions Utilize home dialysis modalities Not available in all regions Decrease weight gain Decrease sodium intake  Dietary counseling, including family members/food preparers  Dietary sodium restriction  Avoid sodium loading during dialysis Patient preferences and adherence; difficult in setting of high-salt diets Limited food choices; poverty; dietician, registered nurse, and physician skills Imprecise dialysate sodium prescriptions; increased cramping and hypotension Enhance nondialytic volume loss  Diuretics  Gastrointestinal, sweat, and respiratory Viable strategy only among individuals with residual kidney function Patient preference and symptom burden; limited evidence Improve tolerability of a specific UF rate Enhance vascular space viability Cooled dialysate Patient tolerance, although data suggest well tolerated May improve single-treatment BP but often leads to more IDWG and volume overload in the long-term Exposure to time-limited higher UF rate; limited evidence Isolated UF, followed by HD Exposure to time-limited higher UF rate; potential decrement in clearance; limited evidence Limited availability of beds for in-center HD Improve overall health Prevent protein energy wasting Chronic intervention that cannot be applied acutely Preserve residual kidney function Chronic intervention that cannot be applied acutely; may occur at the expense of volume overload; limited evidence Intradialytic exercise Chronic intervention that cannot be applied acutely; infeasible in resource-poor regions; limited evidence BP, blood pressure; HD, hemodialysis; IDWG, interdialytic weight gain; UF, ultrafiltration. Kidney Int. Author manuscript; available in PMC 2021 May 01. [/table]
[table] Table 5 |: Hemodialysate composition and blood pressure and volume status Further research needed regarding the optimal serum to dialysate Na + gradient  Further research needed to assess whether lower dialysate Na + Generally avoid very low dialysate Ca ++  Optimal balance between risk of lower BP and increased heart failure and sudden cardiac death risk with lower dialysate Ca ++ needs to be weighed against the potential for increased vascular calcification and chronic loss of vascular elasticity resulting in maladaptive vascular and heart remodeling harm of acetate rather than benefits of varying the dialysate HCO BP, blood pressure; IDWG, interdialytic weight gain; HD, hemodialysis; N/A, not applicable.Kidney Int. Author manuscript; available in PMC 2021 May 01. [/table]
[table] Table 6 |: Residual kidney functionWhen to assess124 Limited consensus about frequency, which ranges from quarterly to far less frequent Limited consensus about frequency; not consistently measured in HD patientsHow to assessMean of urea and creatinine clearance using 24-h urine collection and simultaneous one-off blood sampling125 24-h urine collection only for volume vs. both urine collection and serum samples for clearance determination126  Entire interdialytic period preferable Clearance of urea or creatinine or mean of urea and creatinine  Neutral pH Low GDP solution 76  Diuretics (increase urine volume and thus reduce UF rate, but do not specifically preserve RKF) 55 Low-protein diet with keto acid supplementation 128 RCT evidence  High flux vs. low flux (benefit) 130  Frequent nocturnal dialysis may increase rate of loss (harm) 131 GDP, glucose degradation product; HD, hemodialysis; RAS, renin-angiotensin system; RCT, randomized controlled trial; RKF, residual kidney function; UF, ultrafiltration. Kidney Int. Author manuscript; available in PMC 2021 May 01. [/table]
[table] Table 7 |: Volume-assessment parameters and tools Data supporting associations between physical signs and volume status are weakBlood pressure  Studies suggest weak correlation between BP and volume status  Useful in monitoring patient safety  Minimal data on relative effectiveness of various BP measurements as they relate to volume assessment Lung water ultrasound  Good for evaluating for hypervolemia (but not hypovolemia)  Role in routine volume assessment is under way (NCT02310061) Some challenges in interpretation owing to reading variation across some patient subpopulations Biochemical markers (BNP/NT-proBNP, CD146, cGMP)  Generally low accuracy  Cost is variable and depends upon laboratory availability at centers Kidney Int. Author manuscript; available in PMC 2021 May 01. [/table]