Nephrology Hypertension

Hemodialysis: Prescription and Assessment of Adequacy

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Does this patient have kidney disease requiring hemodialysis?

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What tests to perform?

N/A

How should patients with kidney disease requiring hemodialysis be managed?

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 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.Basic clinical physiology and terminology relevant to the dialysis prescription.

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 covection. 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).

Figure 1.

Sieving coefficient.

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.

Flux: The rate of transfer of a substance across the membrane normalized to the membrane surface area. In the case of dialyzers, flux describes the water permeability of the dialyzer. Membrane pore size, pore number and pore density effects flux with larger porous membranes being termed as high-flux.

Efficiency: In the setting of dialysis efficiency refers to the dialyzers ability to remove solute, in general small solutes such as urea. Higher efficiency dialyzers tend to have a larger surface area.

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.

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/h/mmHg. Dialyzers with higher ultrafiltration coefficients are more permeable to water and often are higher flux dialyzers.

Miscellaneous abbreviations

Qb - Blood Flow (ml/min)

Qd - Dialysate Flow (ml/min)

t - Time

K - Clearance

V - Volume

RRT - Renal replacement therapy

ESRD- End stage renal disease

KoA - Mass transfer area coefficient

Kuf - Ultrafiltration coefficient

D- Daltons

ml - milliliters

min- minutes

mEq - Milliequivalents

L - Liter

What toxins are responsible for the uremic syndrome?

Clearance of uremic retention solutes is one of the principle functions of renal replacement therapy. Most of the known uremic retention solutes are believed to be generated from protein metabolism and/or gut breakdown of amino acids. Urea is generated during protein metabolism, is easily measured and therefore, has become well established as a surrogate marker for the uremic syndrome. Urea itself is not toxic, except at very high levels. Uremic toxins can be described using the terminology below.Solute size, volume of distribution, and amount of protein binding effect the removal of the solute during dialysis.

  • Small molecules: Less than 500 Daltons (D). The prototype small molecule is urea (60 D). Creatinine (131 D) is also a small molecule.

  • Middle molecules: Range in size from approximately 500 D to 2000 D. Surrogate marker for middle molecules is Vitamin B12 (1350 D). Most dialyzer specification sheets will indicate the clearance of B12 which can be used to estimate the efficiency of middle molecule clearance.

  • Large molecules: Greater than 2000 D. β2-microglobulin (11.8 kD) is a large uremic retention solute.

  • Protein bound toxins: Protein bound uremic toxins can be of varying sizes. Majority of the binding occurs to albumin (68kDa) which in essence makes them too large to pass through typical dialysis membranes.

  • Gut-derived toxins: Toxins which are generated in the gastrointestinal tract from microbial breakdown of amino acids.

What are some examples of uremic retention solutes?

When renal function declines, the excretory capacity of the kidney fails and the body accumulates substances that would normally be discarded in the urine by glomerular filtration or tubular secretion. 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.

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. It is believed that the majority of uremic retention solutes are generated during the course of normal protein metabolism or by modifications of amino acids in the gastrointestinal tract by microbial flora, but it is also possible that toxins gain entry into the body via alternate pathways or metabolic processes.

Uremic retention solutes have classically been categorized based on molecular weight. Size comparison has utility in evaluating expected solute clearance during dialysis.

Examples of commonly measured uremic retention solutes:

Small Molecules (< 500 Da)

Urea (measured clinically by blood urea nitrogen, BUN)

Creatinine

Phosphorus

Middle Molecules (2,000-60,000 Da)

Beta-2 Microglobulin

B12 (used as a surrogate middle molecule)

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 renal 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

Dialyzer:

  • High flux, high efficiency (high urea clearance, high B12 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 200 ml/min greater than the Qb is appropriate)

Dialysate Concentrate:

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

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

Heparin anticoagulation:

  • 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

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: 200ml/min

  • Dialysate flow: 300ml/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: 200ml/min

  • Dialysate flow: 500ml/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: 300ml/min

  • Dialysate flow: 500ml/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 provide information about:

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

  • B12 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.Alternatively, dialyzers can 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 secification 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. Increased blood flow will lead to more efficient dialysis and higher solute clearance. Venous catheters as opposed to arteriovenous fistulae and ateriovenous 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.

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

For a stable outpatient prescription, dialysate flows should be set > 200ml/min faster than the blood flow. Above 200 ml/min faster than the blood flow probably does not confer much extra benefit in small solute clearance, however there may be some benefit seen in removal of protein bound solutes when using faster dialysate flow rates.

How does a change in dialysate temperature affect my patient?

Cool dialysate and cool core body temperature has been associated with improvements in intradialytic hypotension. Normal dialysate temperature is 37°C. 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

Anticoagulation

Intravenous unfractionated heparin is typically used for anticoagulation during dialysis therapy. Anticoagulation is often 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 and delivered via an automated pump. The heparin does reach the patient and can result in systemic anticoagulation at high doses.

Often times patients cannot tolerate heparin anticoagulation due to concerns over bleeding risk. In this case, frequent saline flushes can be used. Alternatively, citrate can be added to the dialysate to prevent filter clotting. If citrasate dialysate is not available, regional citrate anticoagulation protocols have been developed and are useful in patients who cannot tolerate heparin.

Options for anticoagulation:

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

  2. Unfractionated Heparin: Low dose: bolus 1000 Units followed by 500 Units/hour. Normal dose: bolus 50-75 Units/kg followed by 5-7 Units/kg/hour.

  3. Citrasate dialysate

  4. Regional citrate protocols

Dialysis needles

Range in size from small (17g) to large (15g). 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. The buttonholing technique leads to a well formed scar tract for placement of needles in the same location during each dialysis session. Once buttonholes are established blunt needles can be used.

Infection control

Hepatitis status (B and C) should be known prior to starting a patient on dialysis. Hepatitis serologies should be 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. TB 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.

Blood pressure support

Hypotension during hemodialysis is a frequent complication. In cases of severe hypotension refractory to discontinuation of ultrafiltration normal saline (NS 0.9%) can be administered to improve systemic blood pressure. This maneuver is usually enough to correct any symptoms of orthostasis. Other less frequently used agents to maintain blood pressure include hypertonic saline and colloid infusions such as albumin and mannitol.

Medications administered with dialysis

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

Medication dosing

Medications should be dosed according to residual renal 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.

  1. Adequacy of solute clearance

  2. Adequacy of volume management

Adequacy of solute clearance

Current methods for evaluating the adequacy of solute clearance focus on urea removal during dialysis.

  • Single pool Kt/V

  • Equilibrated Kt/V

  • Standard Kt/V

  • Urea reduction ratio

  • Computer based urea kinetic modeling

Single pool Kt/V

Clearance of urea (K, ml/min) multiplied by time (t, min) yields a volume of urea removal. If this is normalized to body size by dividing by the volume of distribution of urea (V, ml) the result is a dimensionless parameter known as the single pool Kt/V (Figure 2).

Figure 2.

Single Pool Kt/V (spKt/V).

In vivo, it is difficult to measure K and V, therefore this equation is limited in its use in hemodialysis. Further this equation 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 spKt/V. The following equation (Figure 3) is one example that uses more readily available variables for calculation of a single pool Kt/V.

Figure 3.

Daugirdas II equation for single pool Kt/V (spKt/V.

R = post dialysis urea / pre dialysis urea

t = time (hours)

UF = ultrafiltration (L)

W = Post dialysis weight (kg)

Ln = natural logarithm

Clinical practice guidelines (http://www.kidney.org/professionals/kdoqi/) recommend a minimum standard Kt/V of 2.0 (see below), this roughly equates to a minimum single pool Kt/V of 1.2 (in a patient with minimal residual renal function and on dialysis 3 times weekly). In general, the target single pool Kt/V should be > 1.4.

Limitations of the single pool Kt/V (spKt/V):

  • Neglects compartment effects. Does not account for urea rebound after dialysis. (equilibrated Kt/V helps to address this issue).

  • 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)

  • See: Limitations of urea based methods for determining adequacy of solute clearance.

Equilibrated Kt/V

One major weakness of the single pool model is that the body is not a single pool but rather contains many compartments with variable access to the circulation. Therefore, significant compartmental effects will exist during and shortly after dialysis.

The equilibrated Kt/V attempts to correct the single pool Kt/V by estimating the post dialysis urea rebound. Around 30-60 minutes after dialysis, interstitial and intracellular urea levels have equilibrated with the plasma space. Post dialysis BUN levels drawn 60 min after dialysis would be ideal to assess the amount of dialysis delivered however time constraints and additional phlebotomy make it impractical to accomplish.

Post dialysis urea rebound occurs in phases with access recirculation taking place first (AR), followed by equilibriation of the cardiopulmonary circuit with the rest of the systemic circulation (C APR) and lastly by remote compartment (RC) equilibriation. PUBMED:8072267 The following equations are used to take into account urea rebound after the dialysis session (Figure 4, Figure 5).

Figure 4.

Equilibrated Kt/V (eKt/V) for a patient with a AV access.

Figure 5.

Equilibrated Kt/V(eKt/V) for a patient with a central venous catheter.

Where eKt/V is the equilibrated Kt/V or the Kt/V that is obtained after dialysis is complete and urea has completely redistributed equally among all body compartments, spKt/V is the single pool Kt/V (see above for methods to calculate the spKt/V) and t is time (hours). Different equations are necessary depending upon the access type due to the need to correct for recirculation in the cardiopulmonary circuit seen with arterial access which is not a factor when a venous catheter is used for access.

Limitations of eKt/V:

  • 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

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

  • See: Limitations of urea based methods for determining adequacy of solute clearance.

Standard Kt/V

In order to quantify the amount of dialysis delivered over the period of a week and be able to compare the results among varying treatment frequencies the standard Kt/V (stdKt/V) was developed (Figure 6). The standard Kt/V is a hypothetical continuous urea clearance. By using the urea generation rate and the mean pre-dialysis urea concentration over a period of a week one can calculate a continuous urea clearance normalized to the volume of distribution.

Figure 6.

Formula for the calculation of standard Kt/V (stdKt/V).

Using the stdKt/V allows the comparison of amount of delivered dialysis among different treatment strategies (for example PD and HD) and gets around one of the weaknesses of the spKt/V and eKt/V by quantifying amount of dialysis delivered over multiple treatment sessions as opposed to what is delivered in a single dialysis session. It is also believed to correlate better with middle molecule and protein bound uremic toxin clearances.

KDOQI clinical practice guidelines recommend a standard (weekly) Kt/V urea of 2.0 or greater (when residual renal function < 2 ml/min)

Urea reduction ratio

The fractional reduction of urea during a single dialysis treatment is known as the urea reduction ratio (Figure 7). The URR has the advantage that it is easy to calculate and easy to understand.

Figure 7.

Urea reduction ratio (URR).

Roughly, a URR of 0.65 (or 65% urea reduction) correlates with a spKt/V 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

  • See: Limitations of urea based methods for determining dialysis adequacy

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 in the historical NCDS trial, which is described further below.

Urea kinetic modeling

Urea kinetic modeling utilizes complex mathematical formulae and computers to calculate Kt/V urea. Time needed to achieve desired Kt/V can be determined with urea kinetic modeling. 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) are also often taken into consideration.

Adequacy of volume management

Normalization of blood pressure through control of extracellular fluid volume in dialysis patients can also be considered a measure of dialysis adequacy. 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:

  • Hypertension

  • Peripheral edema

  • Pulmonary edema

  • Jugular venous distention

  • Increased cardiothoracic ratio

  • Failure to achieve dry weight

Methods to decrease extracellular fluid volume:

  • Dietary sodium restriction and avoidance of large intradialytic weight gains

  • Increase ultrafiltration with dialysis (prolong dialysis time or add dialysis sessions)

  • Use of diuretics in patients with residual renal function

  • Avoidance of high sodium dialysate, avoidance of sodium modeling

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/V 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 ECV excess severe)

  • Anorexia / poor appetite

  • Loss of taste sensation

  • Nausea / vomiting

  • Fatigue

  • Hypertension

  • Pruritis

  • Sleep disturbances

  • Neuropathy

  • Anemia refractory to treatment

  • Uremic pericardial effusion

What are some factors that can cause a discrepancy between intended (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)

  • Dialyzer clotting (loss of dialyzer surface area)

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

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

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

  • Overestimation of prescribed dose by use of manufacturer KoA values which are obtained in vitro

Limitations of urea based methods for determining adequacy of solute clearance

  • Dependent upon urea which is influenced by not only by renal function and dialysis but also by diet and protein metabolism as well.

  • Most of the methods do not account for residual renal function which has an effect on the total urea clearance.

  • May overestimate adequacy in smaller persons (smaller V).

  • Urea itself is not toxic except at very high levels. Neglects the myriad 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.

Prescribed vs. delivered dose: clearance data for dialyzers is based on in vitro data that overestimates in vivo clearance. Care should be taken to realize that for the reasons described above, the delivered dose will always be less than prescribed dose.

Ways to change the dialysis prescription to improve the dose delivered

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

  1. Increase dialysis time

  2. Increase dialysis frequency

  3. Increase blood flow

  4. Increase dialysate flow

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

  6. Ensure appropriate dose of anticoagulation to prevent dialyzer clotting

  7. Minimize any potential interruptions in treatment

What happens to patients with kidney disease on hemodialysis?

N/A

How to utilize team care?

N/A

Are there clinical practice guidelines to inform decision making?

N/A

Other considerations

N/A

Table 1.

NCDS Study Parameters
Group TAC(urea) Dialysis time (h)
1 50 4.5 - 5
2 100 4.5 - 5
3 50 3 - 3.5
4 100 3 - 3.5

What is the evidence?

Summary of key studies evaluating dialysis dose

National Cooperative Dialysis study

The 1981 National Cooperative Dialysis Study (NCDS) was a randomized trial comparing time averaged urea concentrations with long and short dialysis times. Patients were divided into four group listed in Table 1.Groups 2 and 4 had higher incidence of uremic symptoms and hospitalizations and were more likely to withdraw from the study. The benefit for longer dialysis was not seen between groups 1 and 3. The NCDS study findings were interpreted by some as suggesting that urea removal is more important than treatment time. This led to the assumption by many clinicians that dialysis time could be shortened so long as urea clearance remained adequate. Notable caveats to the NCDS study include the relatively low urea clearances across all groups, a patient population that was healthier than more recent dialysis populations, and the small size of the study, which prevents mortality comparisons.

Observational studies

Observational studies published in the 1980s-1990s suggested that increased dose of dialysis and utilization of high flux membranes is associated with improved outcomes. As a result, there was a trend towards longer and more frequent dialysis.

Hemodialysis (HEMO) study

This was a 2002 randomized clinical trial to compare high dose dialysis with low dose dialysis and high flux dialysis with low flux dialysis. Low dose group had an eKt/V of 1.16 and the high dose group 1.53. Low flux and high flux groups had similar mean eKt/V (1.34) and significantly different β-2 microglobulin clearances (3 ml/min in low flux group vs. 34 ml/min in high flux group). There was no significant improvement in survival seen between any of the groups. The HEMO results were surprisingly negative when compared to the earlier observational data described above, though it should be noted that on secondary analysis there was some benefit in cardiovascular and cerebrovascular outcomes in the high flux group.

Membrane permeability outcome study group (MPO)

This 2009 study was designed to evaluate the effect of membrane permeability on outcome. Patients were randomized to low flux or high flux dialysis membranes and stratified according to their serum albumin levels. Both groups achieved a minimum spKt/V of 1.2. Patients in the low albumin group (< 4 g/dl) and diabetics had a significant survival advantage when treated with a high flux membrane. This advantage was not seen in patients with higher albumin levels or when the group was compared as a whole.

Frequent Hemodialysis Network Trial (FHN)

This 2010 study randomized subjects to traditional in-center dialysis (3 times weekly) versus more frequent dialysis (six times weekly). Standard Kt/V of 3.54 in frequent group compared with 2.49 in traditional group. More frequent dialysis was associated with improvement in left ventricular mass, hypertension, physical composite health score and phosphorus control. The study was only conducted for 12 months and was underpowered to assess mortality. There was no difference in rates of hospitalization between either group.

Other useful links and citations reviewing dialysis adequacy

Review Articles

"Adequacy of hemodialysis".

"Hemodialysis adequacy: basic essentials and practical points for the nephrologist in training".

"Prescribing and monitoring hemodialysis in a 3-4x/week setting".

"Dialysis Dose and Frequency".

Adequacy Guidelines

http://www.kidney.org/professionals/KDOQI/guideline_upHD_PD_VA/index.htm.

http://www.cari.org.au/dialysis_adequacy_published.php.

http://www.csnscn.ca.

http://www.era-edta.org/page-8-39-0-39-ebpgeuropeanbestpracticeguidelines.html.

http://www.renal.org/Clinical/GuidelinesSection/Haemodialysis.aspx.

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