Quantity Steadiness and Intradialytic Ultrafiltration Price within the Hemodialysis Affected person

Successful treatment of non-Hodgkin’s lymphoma with rituximab and dose-adjusted CHOP therapy in a patient with concomitant end-stage renal disease requiring haemodialysis
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Curr Coronary heart Fail Rep. Writer manuscript; out there in PMC 2018 Oct 1.

Revealed in remaining edited kind as:

PMCID: PMC5693775


, MD1,2 and , MD, MPH, PhD1,2,3,4



Quantity administration in hemodialysis sufferers is commonly difficult. Assessing quantity standing and deciding how a lot fluid to take away throughout hemodialysis, the so-called ultrafiltration charge (UFR), has remained a conundrum.


So far there isn’t a goal evaluation software to find out the wanted UFR throughout every hemodialysis session. Greater quantity overload or greater UFR is related to poor outcomes together with worse mortality and unfavorable scientific outcomes. We advise mixed use of the next standards to find out UFR or post-dialysis goal dry weight: pre-hemodialysis blood strain and its intradialytic adjustments, muscle cramps, dyspnea from pulmonary vascular congestion, peripheral edema, tachycardia or palpitation, headache or lightheadedness, perspiration, post-dialysis fatigue. Limiting fluid and salt consumption – and high-dose loop diuretic use in case of residual kidney perform – will be useful in controlling fluid features. Extra frequent and extra extreme hypotensive episodes are related to poor outcomes together with greater dying danger.

Key phrases: Hemodialysis, mortality, quantity overload, ultrafiltration charge, fluid retention, residual kidney perform


Quantity management and administration in long-term or upkeep hemodialysis (HD) sufferers has been an on-going wrestle for each sufferers and nephrologists alike. Between HD remedies, the inter-dialytic interval, most upkeep HD sufferers will accumulate quantity with their every day meals and fluid consumption as most long-term HD sufferers ultimately lose their residual kidney perform. Due to this fact, nearly all of quantity management or removing with dialysis, often called ultrafiltration, will have to be achieved in the course of the affected person’s brief HD remedies (), sometimes thrice-weekly. This usually requires HD therapy occasions and/or frequency to be elevated which is commonly met with resistance from the affected person’s perspective.

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Depicting components associated to hemodialysis sufferers in fluid steadiness administration. See additionally for checklist of scientific standards

Medical Presentation

In hemodialysis sufferers, fluid features are anticipated in the course of the inter-dialytic dialysis interval. HD sufferers know this as “how a lot are you above your dry weight (DW)” or the burden at which sufferers can not tolerate additional fluid removing.1 This inter-dialytic weight achieve (IDWG) is principally from meals and fluid consumption within the upkeep HD affected person as what goes in, stays in. And with every HD therapy, one vital objective is to take away these fluid features by ultrafiltration and preserve the sufferers DW. Power fluid overload develops as affected person’s fluid features exceed the flexibility of dialysis to ultrafiltrate to the set DW and the affected person’s quantity standing exceeds euvolmia. This could happen by excessive fluid consumption and/or by inaccurate assessments of the affected person’s quantity standing by the nephrologist and HD workers.

Quantity standing assessments are sometimes carried out by clinicians and primarily based on the affected person’s signs and bodily examination findings with doable supplementation of some extra goal measurements. Quantity evaluation usually includes medical workers assessing sufferers with helpful scientific standards in figuring out the necessity for fluid removing with every HD therapy (). Blood strain parameters are sometimes useful in guiding fluid removing. Baseline or pre-HD systolic BP (SBP) which can be excessive (e.g. >160 mmHg) might recommend a better quantity state which may be conscious of fluid removing. Conversely, low pre-HD SBP (e.g. <120 mmHg) might recommend euvolemia or presumably hypovolemia to information HD workers to focus on much less fluid removing or an adjustment in dry weight. Moreover, intradialytic BP adjustments will also be suggestive of quantity standing. SBP will increase throughout dialysis, often called intradialytic hypertension, could also be indicative of hypervolemia necessitating additional fluid removing with dialysis. Notably, the change in pre-HD and post-HD SBP shouldn't be higher than 20–30 mmHg as bigger adjustments in SBP have been related to elevated mortality.2

Desk 1

Advised scientific standards for evaluation and adjustment of ultrafiltration charge (UFR) in hemodialysis sufferers

Take away extra fluid or lower goal dry weight Take away much less fluid or improve goal dry weight Feedback
Baseline systolic BP Excessive, e.g. >160 mmHg Low, e.g. <120 mmHg If sBP will increase 1–2 hrs after HD initiation (intradialytic hypertension), might have extra fluid removing
Intradialytic BP change Not identified Not identified The distinction between pre- and post-HD sBP shouldn’t be bigger than 20–30 mmHg2
Cardiac signs Pulmonary edema (see beneath) Tachycardia, palpitation, chest ache Stope UFR if chest ache is reported
Pulmonary Signs Pulmonary congestion or SOB
CNS signs Lightheadedness Headache in the direction of the tip of HD might recommend must decrease UFR
Musculoskeletal Signs If no cramps If worsening cramps Cramps might occur in the direction of the tip of HD
Perspiration Sweating in the direction of the tip of HD session
Peripheral edema Decrease extremity or sacral edema Not even hint edema at first of dialysis
Inter-dialytic weight achieve Excessive Low Usually, weight achieve between 2 HD session must be lower than <1.5 kg
Residual kidney perform (RKF) If minimal to no residual kidney perform If urine quantity >500 cc/day or Kru>3 ml/min Least UFR is advisable in sufferers with substantial RKF with a view to lengthen preservation of RKF
Urge for food and meals consumption Better urge for food and better protein consumption Diminished urge for food
GI signs Diarrhea or diabetic gastroparesis bouts Least UFR throughout gastroenteritis is advisable

Affected person signs are additionally useful in guiding quantity administration. Shortness of breath (dyspnea) related to pulmonary edema is commonly assessed for by HD workers to find out when elevated fluid removing is critical. Moreover, peripheral edema will be simply assessed for previous to HD to information ultrafiltration. However signs in guiding HD workers for reducing or slowing fluid removing are extra refined together with: tachycardia, palpitations, chest ache, lightheadedness, perspiration (particularly in remaining hours of HD remedy), and the event of muscle cramping. These signs sometimes develop in the direction of the tip of a dialysis therapy and are sometimes a sign of an excessive amount of fluid removing.

Extra issues for quantity administration embody monitoring inter-dialytic weight features, the burden achieve between 2 HD periods. Usually, IDWG must be lower than 1.5 kg (or <20 ml/kg). Excessive IDWG will usually information HD workers to extend fluid removing with every therapy. Supplementary to IDWG, higher reported meals consumption and a robust urge for food additionally information clinicians in growing fluid removing with every HD session. Conversely, if sufferers report poor consumption, diminished urge for food, diarrhea, or bouts of diabetic-related gastroparesis changes to lower ultrafiltration are sometimes made by HD workers.

Different methodologies for assessing quantity embody: inferior vena cava diameter, biochemical parameters, steady blood quantity monitoring, ultrasound of lung, and bioimpedance.3–8 Whereas these methodologies might supply extra “goal” measurements for quantity standing, it’s well-known that they’re nonetheless fraught with errors from calibration and operator interpretation of the findings.

The estimation of every affected person’s quantity standing is a crucial window into guiding nephrologist with quantity administration objectives for every dialysis therapy. And there may be now a rising physique of analysis into the affiliation of quantity standing and dialysis affected person outcomes.

Medical Penalties and Affected person End result

Quantity overload in ESRD sufferers has been a scientific problem that’s related to morbid situations equivalent to decrease extremity edema, anasarca, ascites, pulmonary congestion/edema, hypertension and worsening coronary heart failure.9–11 In reality, ESRD sufferers normally share comparable dangers as coronary heart failure sufferers. Each populations share excessive mortality dangers (20 to 25% in america) principally as a result of cardiovascular etiologies12, expertise continual losing syndrome13–15, and exhibit survival paradoxes together with the weight problems and ldl cholesterol.16–18 Moreover, quantity overload or fluid retention in ESRD sufferers has been noticed to be related to elevated danger of mortality. Kalantar et al. has beforehand proven that in 34,107 hemodialysis sufferers that had greater interdialytic weight features, >1.5 kg of physique fluid between 2 consecutive HD remedies, had greater danger of 2-year mortality for each all-cause and cardiovascular mortality strong for multivariate adjustment and in subgroup evaluation. Whereas HD sufferers with IDWG of <1.0 kg between dialysis treatments had a survival advantage with the lowest cardiovascular death risk. In this study, 86% of HD patients were found to have >1.5 kg IDWG and sufferers youthful in age, male intercourse, having longer dialysis classic, diabetic standing, and bigger physique habitus had been additionally discovered to have greater IDWG. Moreover, improved dietary standing that included greater protein consumption was additionally related to bigger IDWG.19

In a latest research by Zoccali et al., continual publicity to fluid overload was assessed and quantified by physique fluid measurements by way of bioimpedance spectroscopy. Right here the authors discovered that continual fluid overload was related to elevated dying danger in incident hemodialysis sufferers. Dying danger was analyzed by baseline fluid overload and cumulative 1 yr fluid overload publicity to keep away from a survival-bias and look at the cumulative nature of fluid overload, respectively. And in each evaluation Zoccali et al. discovered fluid overload to be related to mortality strong to multivariate adjustment. Moreover, cumulative fluid overload was discovered to have a better affiliation with dying danger with a HR of 1.50 (95% CI 1.38 to 1.64) versus baseline fluid overload HR of 1.26 (95% CI 1.19 to 1.33).20

Quantity overload can also contribute to extend cardiac output and hypertension which can result in improve use of anti-hypertensives. Within the absence of scientific options of quantity overload, hypertension requiring increasingly medicines might itself be the indicator of quantity overload.21 And growing anti-hypertensives, within the setting of quantity overload, might fail in controlling blood strain. In reality, in a single research, the growing use of anti-hypertensives was discovered to be a determinant of poor quantity management and sufferers receiving extra medicines had been more likely to be hypertensive.22

Quantity overload additionally contributes to the preload-related components which will promote left ventricular hypertrophy (LVH) by way of myocardial cell lengthening and eccentric and uneven LV reworking.23, 24 The diploma and persistence of LVH in ESRD sufferers has been strongly related to elevated mortality danger25 and a lower in LVH has been related to a subsequent lower cardiovascular mortality danger26 and discount in non-ischemic cardiac failure charges.27 It has additionally been reported that lowering LV mass has related enhancements with anemia and phosphorus ranges.28 Although there are related advantages of enhancing LVH, it’s unclear if extra aggressive ultrafiltration may stop and/or regress LVH.29

Moreover, quantity overload can also contribute to pulmonary dysfunction together with interstitial edema, airway obstruction30–33 and pleural effusions.34, 35 Power quantity overload can also contribute to the event of pulmonary hypertension the place central fluid overload could be the probably contributing issue.36

As we will see, quantity overload as measured by persistently excessive IDWG or fluid measured by bioimpedance has vital associations with mortality outcomes and scientific penalties. Thus correct evaluation of quantity standing in dialysis sufferers and the therapy of quantity overload are of paramount concern for all of these caring for HD sufferers.

Method to Fluid Administration in HD Sufferers

So, what can we do to fight the results of quantity overload? Step one is to regulate “what goes in”. It might appear apparent to dialysis affected person care suppliers that reducing consumption of salt and fluids can be an “simple” resolution to regulate quantity overload. However as all dialysis care suppliers know, this resolution is something however simple to realize within the HD inhabitants. In dialysis sufferers with vital residual kidney perform, the choice of diuretics might have an additional benefit. Bragg-Gresham et al. had proven the statement that diuretic use was related to decrease all-cause and cardiac mortality danger.37 Now this can be the truth that HD sufferers with residual kidney perform do appear to have a survival benefit.38 However the authors suggest that diuretics use might assist protect RKF by minimizing hypotensive episodes throughout dialysis by managing quantity regularly with diuretics relatively than intermittently with HD remedies.37

The ultimate therapy possibility for controlling quantity standing in ESRD sufferers can be ultrafiltration with HD which is commonly the one out there therapy for quantity management within the majority of HD sufferers (who now not have any RKF). However the query stays, how a lot fluid can we safely pull off with HD? This query has just lately come to nationwide stage within the dedication of dialysis care tips.39, 40 The ultrafiltration charge (UFR), fluid quantity eliminated per hour per affected person DW (mL/hr/kg), has been studied in a number of observational research to elucidate the optimum fluid removing charge throughout HD. Saran et al. discovered that UFR of >10 mL/hr/kg had been related to greater all-cause mortality danger (HR 1.09, p=0.02) however not with cardiovascular (CV) associated mortality41 within the worldwide DOPPs cohort. And extra just lately in a prevalent HD cohort, Flythe et al. discovered that UFR of >13 mL/hr/kg was related to and elevated all-cause and CV mortality danger of 59% and 71%, respectively (p<0.001 for each).42 Lastly, Kim et al. just lately present in a cohort of incident HD sufferers that UFR confirmed a linear affiliation with all-cause and CV mortality the place UFR of ≥10 ml/hr/kg was related to HR (95% CI) of 1.15 (1.10–1.19) and 1.23 (1.16–1.31), respectively.

Ultrafiltration might result in these poor outcomes by inflicting intravascular depletion with ensuing hypotension and lowering coronary blood circulation leading to ischemia or myocardial gorgeous.43, 44 Repetitive insults and gorgeous might then result in ventricular reworking and the results of coronary heart failure44–46 when ejection fraction declines. This ultrafiltration induce hypotension can also result in ischemia to different organs together with the mind47, GI tract48, 49 and kidney. Intradialytic hypotension with ischemia to the kidney can also be a contributing issue to additional lack of residual kidney perform50 which might lead to extra difficulties with quantity administration for HD sufferers.


If greater UFRs are related to worse outcomes and HD sufferers nonetheless require the identical quantity of fluid eliminated with every HD therapy, what’s the resolution to this conundrum? For sufferers already established on dialysis, the best decisions can be to both improve HD therapy run occasions and/or frequency which might each successfully cut back the UFR. However as most nephrologist have skilled, this technique for decreasing UFR is met with vital resistance from the sufferers. In a research by Flythe et al., in 600 HD sufferers surveyed, 12% of sufferers had been keen to have an “further” fourth weekly therapy. In reality, some sufferers valued extra fluid consumption a lot that 21% of sufferers surveyed had been keen to extend therapy occasions by half-hour to accommodate the extra fluid consumption.51

And now, quantity administration might develop into much more difficult as UFR itself is beginning to discover “cutoffs” for use as a dialysis high quality metric.39, 52, 53 With a possible UFR threshold of ≤13 mL/hr/kg, many sufferers, who usually are not keen to increase their therapy occasions or change their every day fluid intakes, will doubtlessly go away their HD remedies quantity overloaded perpetuating a continual quantity overloaded state. The potential results and penalties of a UFR limitation are unknown to us at the moment as our UFR-related research up to now are statement in nature. However it’s affordable to anticipate an elevated frequency of uncontrolled hypertension and volume-related hospitalizations using higher portions of anti-hypertensive medicines and extra hospital days, respectively, if quantity management can’t be adequately achieved.

Preventative methods for managing quantity in HD sufferers could also be optimum methodology for each avoiding mortality dangers with greater UFRs and adequately controlling quantity. From our research in house (brief every day) and nocturnal hemodialysis, now we have realized these modalities are related to a decrease prevalence of LVH54 which can be associated to decreased ultrafiltration-induced hypotension and myocardial gorgeous as these frequent HD modalities would take away fluid extra slowly. Moreover, improved BP management has additionally been reported to be associated to the discount within the extracellular fluid quantity55, 56 briefly every day HD. Extra frequent HD, equivalent to brief every day and nocturnal modalities, might supply a extra physiologic mannequin for fluid removing, avoiding giant shifts in fluid quantity, in sufferers selecting HD as their therapy modality of selection.

An extra preventative technique could be the implementation of incremental HD from the onset of renal alternative remedy. One of many major tenants of incremental HD is to maximise the utility of RKF. RKF has the good thing about improved fluid homeostasis. It permits HD sufferers to require much less whole ultrafiltration volumes and thus decrease UFRs which can result in a discount within the prevalence of intradialytic hypotension and its related problems57, 58 and UFRs related mortality danger.59, 60 Using RKF, equivalent to in PD, sufferers may proceed to make use of diuretics for additional management of their quantity standing. With RKF, sufferers may have probably the most physiologic methodology for sustaining ample quantity administration. Incremental dialysis, which can appear to be in opposition to extra frequent HD modalities, has the same precept good thing about lowering the necessity for added quantity removing with every dialysis therapy.


What we will deduct from the quantity administration of HD sufferers is that fast fluid removing can have dangerous penalties. As such, ample quantity administration on this affected person inhabitants ought to happen at a slower charge for optimizing outcomes. Methods equivalent to fluid and salt restriction and continued use of diuretics in sufferers with vital RKF have proven some profit. However the HD-centered methods of extra frequent HD (e.g. brief every day and nocturnal) and incremental HD with a concentrate on preserving RKF would require additional research of their relationship to ESRD quantity administration.


Compliance with Ethics Pointers

Battle of Curiosity

Jason A. Chou declares no battle of curiosity.

Kamyar Kalantar-Zadeh has obtained honoraria and/or help from Abbott, Abbvie, Alexion, Amgen, American Society of Nephrology, Astra-Zeneca, AVEO, Chugai, DaVita, Fresenius, Genetech, Haymarket Media, Hospira, Kabi, Keryx, Nationwide Institutes of Well being, Nationwide Kidney Basis, Relypsa, Resverlogix, Sanofi, Shire, Vifor, ZS-Pharma, and was the medical director of DaVita Harbor-UCLA/MFI in Lengthy Seashore, CA throughout 2007–2012.

Human and Animal Rights and Knowledgeable Consent

This text doesn’t include any research with human or animal topics carried out by any of the authors.


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