Miscellaneous abbreviations

Qb – Blood Flow (ml/min)

Qd – Dialysate Flow (ml/min)

t – Time

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K – Clearance

V – Volume

RRT – Renal replacement therapy

ESRD- End stage renal disease

KoA – Mass transfer area coefficient

Kuf – Ultrafiltration coefficient

Da – Daltons

ml – milliliters

min- minutes

mEq – Milliequivalents

L – Liter

What causes uremic syndrome?

Uremic syndrome occurs as a result of loss of kidney function. Loss of excretory functions of the kidney leads to accumulation of substances that would normally be excreted in the urine by glomerular filtration or tubular secretion. Loss of endocrine and metabolic function of the kidney has a number of manifestations, including anemia and retention of solutes removed by kidney via other metabolic pathways. Historically the first solute recognized to be retained in persons with kidney failure was urea, hence the terms; uremia and uremic syndrome. Urea, easily measurable as blood urea nitrogen, has appropriately served as a surrogate marker for the uremic condition but it is important to note that urea itself is not responsible for the toxicity witnessed in the setting of the uremic condition.

Numerous compounds of varying size and origin are progressively retained with decline in kidney function, many of these molecules having inherent properties quite different from urea. These substances are collectively referred to as “uremic solutes”. Retention of these uremic solutes likely contributes to many manifestations of uremic syndrome and the solutes causing uremic toxicity are referred to as “uremic toxins”. While work is continuing in this field, at the time of this writing, our knowledge of many of these retention solutes and their removal during dialysis is quite limited. Our knowledge about the source of these toxins is also evolving. The key point to remember is that while hemodialysis is quite effective in removing urea, other uremic solutes are not removed as efficiently.

How are uremic solutes classified?

There are several different ways of classifying uremic solutes.

  • Classification based on solute size: Solutes are classified as small (<500 Da), middle molecules (500 Da to 2,000 Da) and large (>2,000 Da). The prototype small solutes are urea (60 Da) and creatinine (113 Da). Middle molecules include Vitamin B12 (1,355 Da) and β2-microglobulin (11,600 Da). Example of large solute is β-trace protein (23,000-25,000 Da). Most dialyzer specification sheets will indicate urea and middle molecule clearance.

  • Classification based on protein-binding: Protein bound uremic toxins can be of varying sizes. The majority of the binding occurs to albumin (66,000 Da) which in essence makes them too large to pass through typical dialysis membranes. P-cresol sulfate (187 Da) is a protein-bound uremic solute and is >90% protein-bound, limiting removal by dialysis.

  • Classification based on method of production: Solutes are also classified as gut-derived or endogenous, based on the site of production. Examples of gut-derived solutes, generated from microbial breakdown of amino acids, include p-cresol sulfate (187 Da) and trimethylamine-N-oxide (TMAO; 75 Da). Examples of endogenous solutes include urea (60 Da) and asymmetric dimethylarginine (ADMA; 202 Da).

Basic clinical physiology and terminology relevant to the dialysis prescription

Concentration: The ratio of the amount of solute in a given volume. Both generation and removal will affect the concentration of a solute in the body. Solute concentration in plasma is inversely proportional to the removal rate of the solute. In the setting of renal failure, solute removal from the body is impaired and concentration of many solutes rises as the generation of the solute overcomes renal capacity for removal.

Diffusion: Movement of particles from areas of higher solute concentration to areas of lower concentration through random motion. In the setting of dialysis, for example in the case of urea, it is the movement of urea in high concentration in the blood across a semipermeable membrane (dialyzer) to an area of lower concentration in the dialysate. Diffusion during dialysis can also take place in the opposite direction from the dialysate into the blood.

Convection: The movement of molecules within fluids. Also known as solute drag. Occurs during ultrafiltration or hemofiltration. As a transmembrane pressure is applied to the dialyzer a given amount of plasma water is forced through the semipermeable membrane (dialyzer). Any solute dissolved in plasma water is dragged along and subsequently removed from the circulation. The selectivity of the convective process for various solutes depends upon the sieving properties of the membrane, in particular, the solute size and the membrane pore size.

Sieving coefficient: This describes the membrane passage of a particular solute during convection. The sieving coefficient is determined by dividing the concentration of the solute in the effluent by the concentration in the blood. For example, urea (small molecule) generally will have a sieving coefficient of 1 which indicates that the concentration in the blood is equal to the concentration in the effluent whereas albumin, a molecule which is too large to pass traditionally used membranes, will have a sieving coefficient of 0. This is illustrated in Figure 1, where the sieving coefficient is equal to the concentration in the dialyzer effluent (Ce) divided by the concentration in the plasma (Cp).

Clearance: The volume from which a substance is completely removed in a specified period of time. Often expressed in milliliters per minute (ml/min).

Ultrafiltration: The movement of fluid across a semipermeable membrane which is caused by a pressure difference. In dialysis, this usually refers to the volume of fluid that is removed during the dialysis procedure.

Efficiency: Dialyzer efficiency refers to its ability to remove small molecular weight solutes, like urea, and is primarily determined by membrane surface area and permeability. Efficiency is usually reported for clearance of urea.

Flux: Membranes with larger pore size can remove middle molecules such as β-2 microglobulin more efficiently. These membranes are called high flux dialyzers. Generally, high-flux dialyzers also have greater water permeability, often greater than 20 ml/hour per mm Hg.

Ultrafiltration Coefficient (Kuf): Gives information about the water permeability of the dialysis membrane. The Kuf is derived from in vitro experiments evaluating ultrafiltration at varying transmembrane pressures. The ultrafiltration coefficient is listed in units of ml/hour per mm Hg. Dialyzers with higher ultrafiltration coefficients are more permeable to water and often are higher flux dialyzers.

Mass Transfer (KoA): Reflects the maximum clearance of solute across the dialysis membrane when blood and dialysate flows are infinite. Product of membrane mass transfer coefficient (Ko) and area (A). Higher values indicate more efficient dialyzers. The KoA can be used to compare the performance of different dialyzers but is not used to calculate expected clearances clinically.

What is a standard hemodialysis prescription?

The hemodialysis prescription should take into account the goals of the therapy, expected solute clearance needs, volume removal needs, residual kidney function, timing of the therapy and logistical concerns. When initiating dialysis for the first time in a uremic patient, care should be taken to avoid dialysis disequilibrium syndrome.

In dialysis disequilibrium syndrome, cerebral edema can develop as a result of rapid plasma reduction of plasma osmolality leading to a solute gradient between the intracellular and extracellular space which promotes osmotic movement of water into the cellular space leading to cell swelling. For this reason, dialysis should be kept purposefully inefficient during the first 3-4 hemodialysis sessions, followed by maximized efficiency once the patient is on a stable chronic regimen.

What is an example of an appropriate prescription for a stable chronic outpatient dialysis session?

The following is intended to illustrate an example of a prescription for a stable chronic outpatient dialysis session. It may not be applicable to all patients.

Time: 4 hours


  • High flux, high efficiency (high urea clearance, high β-2 microglobulin clearance, high KoA, high Kuf)

Blood Flow (Qb):

  • 300-500 ml/min (as fast as access and hemodynamics allow)

Dialysate Flow (Qd):

  • 500-800 ml/min (typically 1.5-2 times the Qb is sufficient)

Dialysate Concentrate:

  • Sodium 137 mEq/L, Potassium 2 mEq/L, Calcium 2.5 mEq/L, Bicarbonate 35 mEq/L.

  • Dialysate concentrate should be adjusted to fit the patient’s needs based on laboratory values. See below.

Heparin anticoagulation: (not always needed)

  • Low dose: bolus 1000 Units followed by 500 Units/hour

  • Normal dose: bolus 50-75 Units/kg followed by 5-7 Units/kg/hour

Dry weight goal or ultrafiltration goal

  • Determined by dialysis practitioner (ideally ultrafiltration is less than 10-13 ml/kg/hour)

What is an example of an appropriate prescription for initiation of dialysis?

The following is intended to illustrate an example of a prescription for initiation of dialysis to prevent dialysis disequilibrium syndrome. It may not be applicable to all patients.

First Treatment:

  • Time: 2 hrs

  • Dialyzer: Choose smaller, low flux dialyzer with low urea clearance and low KoA

  • Blood flow: 200 ml/min

  • Dialysate flow: 300 ml/min

  • Volume removal: Dependent upon patient volume status

  • Concentrate: Dependent upon patient laboratory values, in general one would use a low bicarbonate and high potassium bath

Second treatment:

  • Time: 2.5 hrs

  • Dialyzer: Choose smaller, low flux dialyzer with low urea clearance and low KoA

  • Blood flow: 200 ml/min

  • Dialysate flow: 500 ml/min

  • Volume removal: Dependent upon patient volume status

  • Concentrate: Dependent upon patient laboratory values

Third treatment:

  • Time 3 hrs

  • Dialyzer: Choose smaller, low flux dialyzer with low urea clearance and low KoA

  • Blood flow: 300 ml/min

  • Dialysate flow: 500 ml/min

  • Volume removal: Dependent upon patient volume status

  • Concentrate: Dependent upon patient laboratory values

If the patient is stable and without complications after the third treatment, continue to advance to a routine outpatient prescription as listed above.

How do I select the appropriate dialyzer?

Dialyzer characteristics and performance vary between manufacturers and models. It is worthwhile to be familiar with the types of dialyzers that are used in the dialysis units where your patients are treated. Dialyzer specification sheets can usually be downloaded easily from the internet via manufacturers websites.

Most dialyzer specification sheets will list clearances from in vitro data collected while testing the performance of the dialyzer in the lab. It should be recognized that in vivo performance will not be as good as listed on the specification sheets and therefore most clinicians do not recommend using this information to determine the dialysis dose or prescription. Even so, the dialyzer specification sheets can give the practitioner a way to compare performance of different dialyzers.

Dialyzer specification sheets usually have the following information

Dialyzer in vitro performance (often listed at different blood flows):

  • Creatinine and urea clearance which can be used to estimate efficiency of small solute removal

  • Vitamin B12, β-2 microglobulin or other middle molecule clearance to estimate efficiency of middle molecule removal

  • KoA (mass transfer area coefficient) or clearance of solute at infinite blood and dialysate flow rates

  • Kuf (ultrafiltration coefficient) describes the flux of the dialyzer or the ability to ultrafilter water

  • Pore sizes: higher flux membranes typically have larger pore sizes

  • Membrane surface area: larger surface area usually means greater efficiency

Dialyzer materials: most dialyzers are composed of “biocompatible” materials such as polysulfone, polyamide or a similar material. Allergic reactions can rarely develop to dialyzer or tubing materials.

Sterilization method: dialyzers usually are sterilized by heat, steam or radiation. Dialyzers can also be sterilized with ethylene oxide but this method of sterilization has fallen out of favor due to an association with allergic reactions and hypotension.

Reuse properties: certain dialyzers can be reused. Performance of the dialyzer is expected to decrease as the dialyzer is reused and looses fiber bundle volume. Dialyzer specification sheets for reuse dialyzers will list clearances at various stages of reuse.

How do I select the appropriate blood flow?

Determination of the desired blood flow during dialysis should take into account the limitations of the dialysis access, desired efficiency of dialysis, and the hemodynamic stability of the patient. Faster blood flows can be associated with hypotension. Generally, higher blood flow will lead to more efficient dialysis and higher solute clearance. Venous catheters as opposed to arteriovenous fistulae and arteriovenous grafts do not support higher blood flows.

In general, it is a good rule of thumb to increase the blood flow to the maximum amount that the patient and dialysis access can safely tolerate. Blood flows during dialysis range from 150 ml/min up to 500 ml/min. Note that a mature fistula has a blood flow rate greater than 600 ml/min.

How do I select the appropriate dialysate concentrate and dialysate flow?

For a stable outpatient prescription, dialysate flows should be set 1.5 times faster than the blood flow. A higher dialysate flow rate does not confer much extra benefit in urea clearance, however there is increased removal of highly protein-bound solutes, such as p-cresol sulfate, when using faster dialysate flow rates.

How does a change in dialysate temperature affect my patient?

Normal dialysate temperature is 37°C. Cool dialysate and lower core body temperature has been associated with lower risk of intradialytic hypotension and cooling dialysate 0.5 °C below body temperature lowers ischemic brain injury. The use of cool dialysate (35.5-36°C) during dialysis to improve hypotension should be balanced against risks which include patient discomfort and increased incidence of dialyzer clotting.

Some other considerations when prescribing dialysis


Intravenous unfractionated heparin may be used for anticoagulation during dialysis therapy. Anticoagulation can be needed to keep the hemodialysis circuit and filter patent. Areas prone to clotting in the hemodialysis setup include the hollow fibers of the dialyzer, the dialyzer header and the venous drip chamber. Heparin infusion during dialysis is often given via a side branch in the arterial portion of the circuit into the blood going to the dialyzer and delivered via an automated pump. The heparin does reach the patient and can result in systemic anticoagulation at high doses.

If heparin anticoagulation is not feasible due to bleeding risk, frequent saline flushes can be used. Alternatively, citrate can be added to the dialysate to prevent filter clotting. If citrate dialysate is not available, regional citrate anticoagulation protocols can also be used but require close monitoring of serum calcium and repletion if hypocalcemia occurs.

Options for anticoagulation:

  • Saline flushes, 200 ml via circuit every 30 min – 60 min as needed to prevent clotting. Ultrafiltration must be adjusted to remove the extra volume delivered to the patient.

  • Unfractionated Heparin: Low dose: bolus 1,000 Units followed by 500 Units/hour. Normal dose: bolus 50-75 Units/kg followed by 5-7 Units/kg/hour.

  • Citric acid containing dialysate

  • Regional citrate protocols

Dialysis needles

Range in size from small (17 gauge) to large (15 gauge). Whenever possible larger needles are used for dialysis as they permit higher blood flows. Smaller needles should be reserved for access that is newly cannulated, difficult access or patients with bleeding problems. Generally, dialysis needles used are sharp needles and are used to puncture a different point of fistula or graft with each stick. An alternative approach is to use blunt tip needles and “button holes”. Button holes are created by repeatedly using the same site for cannulation with a sharp needle till a well formed scar tract is in place. Once the button hole is established, blunt needles can be used. However, it is important to note that several recent studies have reported higher risk of infections in patients using button holes compared to those using sharp needles.

Infection control

Hepatitis status (B and C) should be known prior to starting a patient on dialysis. Hepatitis serologies are repeated periodically and also when patients transfer to a different dialysis unit. Patients with positive hepatitis B surface antigen require specific isolation procedures during dialysis. Tuberculosis status should also be assessed with a PPD prior to initiation of dialysis. For more information the reader is referred to the Centers for Disease Control and Conditions for Coverage from the Centers for Medicare and Medicaid Services.

Intradialytic hypotension

Hypotension during hemodialysis is a frequent complication. In cases of severe hypotension refractory to discontinuation of ultrafiltration, normal saline can be administered to improve systemic blood pressure. Other less frequently used agents include hypertonic saline and colloid infusions such as albumin and mannitol. In some patients, α-adrenergic agonist midodrine may also be useful.

Medications typically administered with dialysis

Common medications that may be administered with the hemodialysis procedure include erythropoiesis stimulating agents (ESAs), vitamin D analogues, intravenous iron, L-carnitine and heparin.

Medication dosing

Medications should be dosed according to residual kidney function and expected clearance with dialysis. In general, medications with a low volume of distribution and a low level of protein binding will be readily cleared with dialysis whereas medications with a high volume of distribution and a high level of protein binding will not be as readily removed with the dialysis procedure. Medications that are cleared with dialysis should be re-dosed after the dialysis session.

How is the adequacy of dialysis assessed?

The two main functions of dialysis are removal of uremic retention solutes and the removal of excess fluid that accumulates in the setting of kidney failure. These two goals are accomplished during hemodialysis in different ways. Therefore, in order to assess the adequacy of the therapy, one can split these two functions into separate categories, both of which must be addressed in order for the patient to achieve an adequate amount of therapy.

  • Adequacy of solute clearance

  • Adequacy of volume management

Adequacy of solute clearance

Current methods for evaluating the adequacy of solute clearance focus on urea removal during dialysis. In general, to assess clearance, urea removal during dialysis is estimated and indexed to the volume of distribution of urea (total body water, TBW). The different metrics used to assess solute clearance are described below; in important consideration in using these metrics is postdialysis urea rebound.

Postdialysis urea rebound

The urea level in plasma is lowest immediately at the end of dialysis. In the 30-60 minutes after dialysis, interstitial and intracellular urea levels equilibrate with the plasma space resulting in a higher plasma level. This phenomenon is called postdialysis urea rebound and it occurs in phases with access recirculation taking place first, followed by equilibration of the cardiopulmonary circuit with the rest of the systemic circulation, and lastly by remote compartment equilibration. This remote compartment is primarily composed of muscle.


Clearance of urea (K, ml/min) multiplied by time (t, min) yields the volume cleared of urea during a dialysis treatment. This is normalized to the volume of distribution of urea (V, ml) the result is a dimensionless parameter known as the Kt/Vurea. In vivo, it is difficult to measure K and V, and considering only urea removal does not account for urea generation during dialysis or fluid removed during the dialysis procedure (changing V). To address some of these limitations, several equations have been developed through regression analysis for the calculation of Kt/Vurea.

The major limitation of all Kt/Vurea derivatives is that they assume that adequate urea clearance during dialysis equates with adequate removal of all uremic toxins, which is not the case as protein-bound and highly compartmentalized (sequestered) solutes are not removed efficiently even though urea removal may be adequate.


This metric is calculated using urea levels before and immediately after dialysis initiation. It assumes that urea is in a “single pool” or compartment. For patients that are dialyzed thrice weekly, the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) 2015 hemodialysis adequacy guidelines (https://www.kidney.org/professionals/guidelines/hemodialysis2015) recommend a target spKt/Vurea of 1.4 and a minimum “delivered” spKt/Vurea of 1.2. This dose can be reduced in patients with significant residual kidney function provided that the residual kidney function is closely monitored. The following equation is recommended by the 2015 KDOQI hemodialysis adequacy guidelines for calculating spKt/V urea in patients undergoing thrice weekly hemodialysis:

spKt/Vurea = –ln(R–0.008 x T) + (4-3.5 x R) x 0.55 x Weight loss/V

R = postdialysis urea / predialysis urea

T = duration of dialysis treatment (hours)

Weight loss = Postdialysis weight – predialysis weight, converted to L (note 1 kg = 1L)

V = Total body water volume, calculated using Watson equation (L)

ln = natural logarithm

Limitations of the spKt/Vurea include the following:

  • Does not account for postdialysis urea rebound.

  • Evaluates adequacy of only a single treatment.

  • Results cannot be easily compared when using different treatment frequencies and durations (standard Kt/V urea helps to address this issue)

Equilibrated Kt/Vurea (eKt/Vurea)

The eKt/Vurea attempts to correct the single pool Kt/V by estimating the postdialysis urea rebound. Post dialysis urea levels, drawn 60 min after dialysis, would be ideal to assess urea rebound, however, time constraints and additional phlebotomy make it impractical to accomplish. The following equation is recommended by the 2015 KDOQI hemodialysis adequacy guidelines for calculating spKt/V urea in patients undergoing thrice weekly hemodialysis:

eKt/Vurea = spKt/Vurea x t/(t+30)

t = duration of dialysis treatment (minutes)

Limitations of eKt/Vurea include:

  • Evaluates adequacy of only a single treatment.

  • Results cannot be easily compared when using different treatment frequencies and durations (standard Kt/V helps to address this issue).

Standard weekly Kt/Vurea (stdKt/Vurea)

This metric allows comparison of the amount of dialysis urea clearance delivered over the period of a week by different dialysis modalities and by different hemodialysis frequencies and duration (for example, twice weekly, short daily, and nocturnal hemodialysis). The stdKt/Vurea is a hypothetical continuous urea clearance that is comparable across modalities and treatment regimens. This metric also allows for incorporation of dialysis urea clearance and urea clearance from residual kidney function. The KDOQI 2015 Hemodialysis Adequacy Guidelines recommend a target stdKt/Vurea of 2.3 per week and a minimum delivered stdKt/Vurea of 2.1 per week. The KDOQI 2015 Hemodialysis Adequacy Guidelines recommend StdKt/Vurea calculation as follows:

stdKt/Vurea = Residual stdKt/Vurea + Dialysis stdKt/Vurea

Residual stdKt/Vurea = Urea Clearance in ml/min * 10,080 / v

Dialysis stdKt/Vurea = S / [1-0.74/F (Weekly ultrafiltration Volume/v)]

S =

10080 * 1-e–eKt/V


/eKt/V + 10080/Nt –1


Weekly ultrafiltration Volume in ml

v = Total body water volume, calculated using Watson equation (ml)

F = Number of dialysis treatments per week

t = duration of dialysis treatment (minutes)

Surface Area Normalized Kt/V (SAstdKt/Vurea)

This equation attempts to correct for under dosing of dialysis that can occur in women and smaller sized persons if the clearance (Kt) is normalized to total body water (V). The clearance (Kt) can also be normalized to body surface area. The resulting SAstdKt/Vurea can be calculated as follows:

SAstdKt/Vurea = (stdKt/V/20) * (V/Body Surface Area)

V = Total body water volume, calculated using Watson equation (L)

Body Surface Area is calculated using the Dubois formula based on height and weight (m2)

There are no specific guidelines for targeting SAstdKt/Vurea but a value of 2.45 could be considered as the target. This value was the mean SAstdKt/Vurea in the Hemodialysis trial for men in the conventional dose group and women in the high dose group – these subgroups had a trend towards lower mortality in the Hemodialysis trial.

Urea reduction ratio

The fractional reduction of urea during a single dialysis treatment is known as the urea reduction ratio (URR). The URR has the advantage that it is easy to calculate and easy to understand. It is calculated using the following formula:

URR = 1 – (Postdialysis BUN/Predialysis BUN)

Roughly, a URR of 0.65 (or 65% urea reduction) correlates with a spKt/Vurea of 1.2. Target URR for hemodialysis patients is above 0.65.

Limitations of URR:

  • Neglects compartment effects, if drawn immediately after dialysis it does not account for urea rebound.

  • Does not account for urea generation that occurs during dialysis

  • Does not account for volume removal with dialysis (changing V)

  • Evaluates adequacy of only a single treatment

Time averaged concentration of urea (TAC urea)

Urea exposure can also be described as an average concentration over time by averaging the pre and post dialysis urea levels. This has the added advantage of including a larger time frame but the drawback of inability to describe peak and trough urea levels as well as inability to describe the efficiency of the dialysis procedure or amount of urea reduction during dialysis. The time averaged urea concentration was used as a treatment target in the historical National Cooperative Dialysis Study (NCDS), which is described further below.

Urea kinetic modeling

Urea kinetic modeling utilizes complex mathematical formulae and computers to calculate Kt/Vurea. Time needed to achieve desired Kt/Vurea can also be determined. In vitro clearance data provided by a dialysis manufacturer for K, urea generation rate and calculations of volume of distribution based on anthropometric data are utilized. Urea kinetic modeling takes into account volume changes during dialysis as well as urea generation during dialysis. Residual kidney function and normalized protein catabolic rate (nPCR) can also be taken into consideration.

Adequacy of volume management

Normalization of blood pressure (BP) through control of extracellular fluid volume in dialysis patients can also be considered a measure of dialysis adequacy. It is important to note that randomized controlled trial data guide BP treatment targets in the general population. No such trial data are available for dialysis patients and the “optimal” BP target in dialysis patients is opinion-based.

Fluid gain in dialysis patients is predominantly secondary to salt and fluid intake and fluid loss in dialysis patients is predominantly through ultrafiltration and residual kidney function. The “dry” weight is the weight that reflects an extracellular fluid volume small enough to render the dialysis patient normotensive and unable to tolerate any anti-hypertensive medications. It is also the point at which further ultrafiltration would lead to symptomatic hypotension. In order for dialysis therapy to be considered adequate, the dry weight must be consistently achieved.

Signs of inadequate volume management include:

  • Uncontrolled hypertension

  • Manifestations of increased total body water such as peripheral edema, pulmonary edema, and jugular venous distention

  • Increased cardiothoracic ratio on X-ray

  • Failure to achieve dry weight

Methods to decrease extracellular fluid volume:

  • Use of high dose loop diuretics in patients with residual kidney function

  • Dietary sodium and water restriction to avoid large interdialytic weight gains

  • Increase ultrafiltration with dialysis (longer dialysis time or add extra dialysis sessions)

  • Avoidance of high sodium dialysate and sodium modeling

What is incremental dialysis?

Incremental dialysis is a dialysis prescription that provides small solute clearance (urea clearance) designed to supplement patients’ residual kidney function. Using this approach, the stdKt/Vurea target is still the same (goal, 2.3; delivered 2.1) but the residual kidney urea clearance is factored into calculating the total urea clearance (stdKt/Vurea). Incremental dialysis allows dialysis frequency and duration to be adjusted as residual kidney function changes.

How do I assess residual kidney function?

Residual kidney function is measured in clinical practice using timed urine collection. Urine collection can be considered for patients that self-report at least 1 cup of urine (~250 ml) daily. There are two different approaches for timed urine collection:

  • Interdialytic interval (44-hour to 68-hour) urine collection: Using this approach, all urine produced during this interval is collected. Average plasma concentration of urea can either be calculated by the average of postdialysis urea level at the start of urine collection interval and the predialysis urea level at the end of collection. An alternate approach is to only obtain predialysis urea level at the end of collection and assume that the average level was 90% of this level (predialysis BUN * 0.9). The major limitation of this approach is its cumbersome nature and high risk errors due to under-collection (missed voids).

  • 12 hour urine collection immediately preceding dialysis: This approach shortens the duration of collection and reduces the chances of error. Plasma concentration of urea is measured at the start of dialysis and used for calculation of urea clearance.

The residual urea clearance is calculated using the following formula:

Residual Urea Clearance in ml/min = [Urine Urea Nitrogen (mg/dL) * Urine Volume (ml)] / [Blood Urea Nitrogen (mg/dl) * Time (minutes)]

How often should the dose of dialysis be measured?

Typically, the delivered dose of dialysis is checked at least once monthly. Measurement of pre and post dialysis urea levels allow calculation of Kt/Vurea or Urea reduction ratio as described above. This information is most useful when compared to historical values to check for a discrepancy between current and previous values in order to analyze trends and less useful when evaluated alone as a “snapshot.”

What are some of the signs and symptoms of inadequate dialysis?

  • Weight loss (or gain if extracellular volume excess is severe)

  • Persistent uremic symptoms, including anorexia, loss of taste, nausea/vomiting, fatigue, pruritus, neuropathy, sleep disturbances, and restless legs.

  • Uncontrolled hypertension

  • Anemia refractory to treatment

  • Uremic pericardial effusion

What are some factors that can cause a discrepancy between prescribed and delivered dose?

  • Actual treatment time is less than prescribed (treatment interruptions, frequent alarms stopping pump, early termination, elective termination)

  • Access recirculation (access stenosis, clotting, central stenosis, needle placement)

  • Blood flow rate lower than prescribed due to problems with dialysis access.

  • Blood pump problems (inaccurate calibration, inadequate occlusion of rollers on tubing, error in setting flow rate)

  • Dialyzer clotting (loss of dialyzer surface area)

  • Dialysate flow problems (inaccurate calibration, error in setting flow rate)

  • Error in draw of pre or post dialysis BUN (saline in line, pre sample drawn after hemodialysis started, needles reversed, fistula recirculation, post sample drawn too early or too late, lab error)

  • Overestimation of prescribed dose by use of manufacturer in vitro KoA values: clearance data for dialyzers is based on in vitro data that overestimates in vivo clearance.

Limitations of urea based methods for determining adequacy of total solute clearance

  • In patients with normal kidney function, glomerular filtration rate provides a general assessment of total solute clearance.

  • In dialysis patients, dialysis urea clearance or Kt/Vurea only assesses one small solute clearance (clearance) and does not provide a general assessment of total solute clearance.

  • Urea-based methods that do not account for residual kidney function underestimate total urea clearance.

  • Indexing of clearance (Kt) to volume of distribution of urea (V; total body water) overestimates adequacy in smaller persons and in women (smaller V).

  • Urea itself is not toxic except at very high levels. Neglects other uremic toxins.

  • Does not address middle molecule or protein bound uremic toxin clearance.

  • Sampling error: if pre or post dialysis BUN is not drawn correctly results can be easily misinterpreted.

Ways to change the dialysis prescription to increased delivered dialysis dose (spKt/Vurea)

Assuming that there are no problems with the dialysis access, the following changes to the dialysis prescription can result in improved solute removal:

  • Increase dialysis time

  • Increase dialysis frequency

  • Increase blood flow

  • Increase dialysate flow

  • Select a dialyzer with: larger surface area, higher flux, higher KoA

  • Ensure appropriate dose of anticoagulation to prevent dialyzer clotting

  • Minimize any potential interruptions in treatment

How to utilize team care?

Dialysis clinics are staffed with nurses, technicians, social workers, dieticians, biomedical engineering personnel, and administrators. Routine group meetings with review of patient and clinic issues can improve process of care.

Are there clinical practice guidelines to inform decision making?

USA (2015): National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) 2015 hemodialysis adequacy guidelines: https://www.kidney.org/professionals/guidelines/hemodialysis2015

Canada (2006): Canadian Society of Nephrology: http://jasn.asnjournals.org/content/17/3_suppl_1/S4.full

Europe (2007): European Best Practice Guidelines (EBPG): https://doi.org/10.1093/ndt/gfm022