Dialysis adequacy

Urea kinetic modelling (UKM)

Urea kinetic modelling is a way of describing and simulating the combined effects of urea removal and urea generation while accounting for the total distribution of urea in the body. It therefore provides information about both solute—or urea—clearance and nutrition. Kt/V is part of the model, but formal UKM also evaluates residual kidney function and the urea generation rate. It can be used to predict how changes in variables such as dialyser size or type and treatment duration will affect solute removal.

Many dialysis machines now include software that calculates Kt/V and collects the relevant data, such as blood flow, treatment time, ultrafiltration rate, and pre- and post-dialysis urea concentrations.

In principle, Kt/V appears straightforward: t is the duration of dialysis and can be measured directly; V is the volume in which urea is distributed and is estimated from body size, height, or body-surface area; and K is the dialyser urea clearance.

It is important to distinguish the prescribed dialysis dose from the dose actually delivered. Estimated V may differ from the patient’s true urea-distribution volume, and the dialyser clearance measured in a laboratory may differ from its performance in vivo.

Formal UKM uses data collected over two dialysis sessions to estimate the rate of urea clearance during dialysis and the rate of urea generation between sessions.

The required observations include pre- and post-dialysis urea during one session in a specified week, the pre-dialysis urea concentration before the second session, pre- and post-dialysis weight for the first session, and the actual dialysis time in minutes.

Correct blood sampling is essential. The post-dialysis sample must not be diluted by saline used to rinse the circuit or affected by recirculated blood. A falsely low post-dialysis urea concentration will overestimate the dialysis dose delivered.

The sample should be obtained using a validated slow-flow or stop-flow method. The source describes sampling within one to two minutes after the pump speed is reduced so that the earliest recirculation-related component of urea rebound is accounted for and arterial and venous concentrations are closer to equilibrium.

Mathematical models can estimate the post-rebound serum urea concentration after redistribution and incorporate it into UKM. If the patient still produces urine, a timed 24- to 48-hour urine collection can be included to estimate residual kidney function and add its contribution to the total dialysis dose.

The fall in urea during dialysis depends on both K and V, because urea redistributes from different body compartments during treatment. The rise in urea between sessions depends on V and on the urea generation rate.

Most conventional UKM uses the immediate post-dialysis urea value as the post-treatment concentration; this is the single-pool model. In reality, blood urea rises again—“urea rebound”—for approximately 45–60 minutes after treatment because urea redistributes from tissues.

Some UKM techniques use double-pool models that explicitly include rebound, although the clinical importance of this refinement remains uncertain.

Residual kidney function should be included in any assessment of the total dialysis dose. It can contribute substantially during the first months of haemodialysis.

Blood sampling for UKM

Pre-dialysis sample from an AV fistula or AV graft: obtain the sample directly from the access needle before dialysis begins.

Post-dialysis sample:

• Stop ultrafiltration by setting the UF rate to zero.

• Reduce blood flow to 50 mL/min for at least 10 seconds.

• Stop the blood pump.

• Draw the sample within the next 20 seconds.

• Alternative slow-flow method: reduce blood flow to 100 mL/min, wait 15–30 seconds, and obtain the sample from the arterial line.

• Second alternative: stop dialysate flow while keeping the blood pump running, wait five minutes, and then obtain the blood sample from the circuit.

For single-needle dialysis, connect the blood lines, discard the first blood corresponding to the dead-space volume, and then obtain the samples.

Dialysis through a percutaneous catheter: discard the first 10 mL of blood from the catheter and then obtain the pre-dialysis sample. Obtain the post-dialysis sample 30 seconds after slowing the pump.

Calculating dialysis adequacy: Kt/V

Single-pool Kt/V (spKt/V) can be calculated from pre- and post-dialysis urea concentrations obtained around one treatment, together with session duration and ultrafiltration volume.

One validated equation over a Kt/V range of approximately 0.7–2.0 is the second-generation Daugirdas formula:

spKt/V = −ln(R − 0.008 × t) + (4 − 3.5 × R) × UF/W_post

Here, R = U_post/U_pre; U_post is post-dialysis urea; U_pre is pre-dialysis urea; t is dialysis time in hours; UF is the amount of weight lost during treatment, equivalent approximately to W_pre − W_post in litres when weights are in kilograms; and W_post is post-dialysis weight. A fixed value of 0.03 is sometimes used as a simplification in place of 0.008 × t.

Kt/V may underestimate the physiologically appropriate dialysis dose in women, particularly when body-surface area rather than urea-distribution volume is considered as the scaling denominator.

Several less accurate approximations derive Kt/V from the urea reduction ratio (URR). One equation quoted in the source is:

Kt/V = 2.2 − 3.3 × [U_post/U_pre − 0.03 − (W_pre − W_post)/W_post]

This is described as reasonably accurate over a URR range of 55%–75%, although it tends to underestimate Kt/V.

Other approximate equations are:

Kt/V = (0.026 × PRU) − 0.46

or

Kt/V = 0.024 × PRU − 0.276

PRU is the percentage reduction in urea during the session. As broad approximations, a URR of 50% corresponds to a Kt/V of about 0.8, 58% to about 1.0, and 65% to about 1.2.

Equilibrated Kt/V

Equilibrated Kt/V (eKt/V) is increasingly reported alongside or instead of simple single-pool Kt/V, although unequivocal evidence that it is the preferable outcome measure is lacking. The source gives the following estimating equations:

eKt/V = arterial spKt/V − (0.6 × arterial spKt/V ÷ t) + 0.03

when an arteriovenous access is used, or:

eKt/V = venous spKt/V − (0.47 × venous spKt/V ÷ t) + 0.02

when a catheter is used.

Other ways to estimate clearance or dialysis adequacy

Unnormalised Kt

Some investigators have proposed that body size, represented by V, may influence outcomes directly and independently of its effect on calculated urea clearance.

This proposal arose partly from observations in the United States that Black patients receiving haemodialysis, and larger patients, sometimes had better survival despite lower relative URR values than White or smaller patients.

Higher Kt/V values have also been associated observationally with higher mortality in some groups, possibly because a small V can reflect malnutrition. This pattern was not seen in the same way when unnormalised Kt was compared with outcome, so unnormalised Kt has increasingly been considered as a complementary measure.

Kt also emphasises the importance of treatment time itself. Observational evidence has associated even modestly shorter dialysis sessions with higher mortality independently of small-solute clearance.

Urea reduction ratio (URR)

URR is the simplest measure of the fall in urea during dialysis. It does not include session duration, ultrafiltration, or body size, but it correlates with Kt/V and remains clinically useful.

URR = (1 − U_post/U_pre) × 100

Equivalently: URR = (U_pre − U_post)/U_pre × 100.

Solute removal index

The total amount of urea removed during a treatment can be measured from the concentration and total volume of spent dialysate. This method does not require blood samples, but it has not been validated as extensively as standard measures and requires collection or accurate measurement of the entire volume of spent dialysate.

Quantifying clearance in haemodiafiltration

Assessment of haemodiafiltration (HDF) must account for both diffusion and convection produced by ultrafiltration.

Small-solute clearance is generally assessed with Kt/V as in conventional haemodialysis, together with the effective convection volume—the total undiluted volume ultrafiltered during treatment. In pre- and mid-dilution HDF, the measured ultrafiltration volume must be corrected for the degree of dilution by an appropriate dilution factor.

Online measurement of clearance

Dialysis machines can estimate Kt/V or urea clearance automatically by several methods:

• Online urea sensing: spent dialysate passes through a urease column and the amount of removed urea is measured or calculated. URR and Kt/V can then be calculated in real time with conventional equations.

• Online ionic dialysance: an automated estimate of ionic exchange between blood and dialysate correlates with urea clearance. A biosensor in the dialysate pathway, such as Diascan™, can provide repeated or continuous estimates of Kt/V based on an assumed V.

• Dialysate conductivity is measured at the inlet and outlet. The resulting estimate of ionic transfer during dialysis correlates with urea clearance.

• Ultraviolet absorbance: continuous measurement of the ultraviolet absorbance of spent dialysate can estimate the removal of retained solutes over time and provide an estimate of Kt/V.

Residual kidney function

Residual renal urea clearance (Kru)

When haemodialysis is first started, residual kidney function may contribute substantially to total solute clearance. In every patient who still produces urine, Kru can be calculated from a timed urine collection lasting 24 hours or, preferably, the approximately 44-hour interval between two dialysis sessions over the weekend. Patients must collect all urine passed during the interval and record the times accurately.

Kru (mL/min) = [urine urea concentration × urine volume (mL)] ÷ {[(plasma urea¹ × 0.25) + (plasma urea² × 0.75)] × collection time (min)}

For thrice-weekly haemodialysis, plasma urea¹ is measured at the beginning of the collection—at the end of the first dialysis session—and plasma urea² at the end of the urine-collection interval.

Kru can be incorporated into a combined dialysis-dose measure often called equivalent renal clearance or a total weekly clearance measure, although simply adding renal and dialytic Kt/V presents mathematical difficulties.

The source gives the following historical approximations, where the combined value equals dialytic Kt/V when no residual function remains:

For haemodialysis three times weekly: total Kt/V = dialysis Kt/V + (5.5 × Kru/V)

or alternatively:

Total Kt/V = dialysis Kt/V + 5.9 × dialysis Kt/V × Kru

Whether such a combined value can be treated as directly equivalent to dialytic Kt/V when defining underdialysis remains uncertain. Residual kidney function may provide benefits that intermittent haemodialysis does not fully reproduce.

Numerous observational studies have shown a strong association between preserved residual kidney function and better survival in both haemodialysis and peritoneal dialysis.

Residual kidney function often declines rapidly after haemodialysis begins.

Other indicators of dialysis adequacy

• Acid–base control: acidosis should be corrected so that pre-dialysis serum bicarbonate is in an appropriate range. Bicarbonate transfer during dialysis is related to URR and Kt/V. Dialysate bicarbonate can be individualised according to the degree of acidosis.

• Ultrafiltration and volume: fluid removal should be sufficient to maintain an appropriate volume state. Increasing oedema or ascites increases V and therefore reduces Kt/V unless K or t also increases.

Adequate treatment time is also needed to permit vascular refilling from the interstitial compartment during dialysis.

• Nutrition: malnutrition is an important possible sign of inadequate dialysis and must always be considered.

Early loss of body tissue can be masked by fluid retention if target weight is not reduced in line with the loss of muscle mass.

• Some dialysis organisations use composite quality scores to compare performance between units.

One example described in the source is a DaVita quality index combining mean Kt/V, haemoglobin, parathyroid hormone, phosphate, albumin, a standardised mortality ratio, and the proportion of haemodialysis patients using a central venous catheter.

• The “HD product” has also been proposed as a simple indicator of dialysis intensity:

HD product = hours per dialysis session × (sessions per week)²

The source proposes a minimum value of 72—for example, 8 hours × (3 sessions/week)², or 2 hours × (6 sessions/week)².

This construct emphasises treatment time and frequency rather than small-solute clearance alone, reflecting their role in middle- and larger-molecule removal, blood-pressure control, and other outcomes. The formula and threshold imply that 4 hours three times weekly would always be inadequate; this is a historical proposal rather than a universally accepted modern adequacy standard.

Protein catabolic rate

The protein catabolic rate (PCR), usually normalised to body weight and then termed nPCR in g/kg/day, is derived from the urea generation rate and is commonly calculated as part of UKM.

• nPCR can also be estimated from nomograms relating serum urea, nPCR, and total urea clearance.

• Urea generation is not a pure measure of dietary protein intake, although it is often interpreted that way. Increased breakdown of muscle also raises nPCR even when protein intake has fallen.

• The source states that nPCR below 0.8 g/kg/day is associated with greater morbidity and mortality. It then gives a value below 1.0 g/kg/day for maintaining positive nitrogen balance; because the direction of this second inequality appears internally inconsistent, it should not be used as a treatment target without checking the current unit protocol and nutrition guidance.

• A low nPCR should prompt careful assessment for protein–energy wasting and inadequate nutritional intake.

An approximate historical calculation is:

PCR = (pre-dialysis blood urea nitrogen − post-dialysis blood urea nitrogen) × (0.045/T)

where T is the number of days between the blood samples.

Dialysis targets

There is no single universally accepted way to calculate Kt/V, and no one number captures every component of adequate dialysis.

Kt/V should not be used as the sole criterion for judging whether haemodialysis is adequate.

The HEMO trial answered important questions but also generated further debate. In patients receiving haemodialysis three times weekly, it did not show a benefit from increasing spKt/V beyond approximately 1.3.

Kt/V

The National Cooperative Dialysis Study (NCDS), a prospective randomised but relatively short study, associated a low dialysis dose—often expressed historically as a Kt/V below approximately 0.8—with increased treatment failure and morbidity.

There is substantial evidence that delivering an adequate dialysis dose matters. It remains less clear whether benefit continues indefinitely as dialysis intensity rises or whether one precise lower threshold reliably identifies underdialysis for every patient.

Once a sufficient level of urea clearance has been reached, other factors such as volume and blood-pressure control may become more important determinants of outcome.

Guidelines from organisations including the UK Kidney Association and US KDOQI have used a minimum delivered spKt/V of 1.2 for conventional haemodialysis three times weekly. Because this is a minimum rather than an ideal average, a dialysis unit’s median or mean delivered value must be appreciably higher for most patients to meet it consistently.

A prescribed spKt/V of approximately 1.3 may be required to ensure that a delivered minimum of 1.2 is achieved.

An spKt/V of 1.2 still provides only a fraction of continuous native kidney clearance. It corresponds approximately to an eKt/V of 1.05 and, depending on sampling and ultrafiltration, a URR near 65%–70%.

The European target cited in the source is an spKt/V of at least 1.4, equivalent to an eKt/V of at least 1.2, for haemodialysis three times weekly. Women and people with a smaller urea-distribution volume may need a higher scaled target.

High-flux haemodialysis may produce more post-dialysis urea rebound, so immediate single-pool calculations can overstate the equilibrated dose. This is one reason to interpret spKt/V together with treatment time and, when relevant, eKt/V.

Higher weekly dialysis intensity is common in countries and centres using longer treatments and has been associated observationally with lower mortality. The historical example of Tassin in France used low-flux cellulose dialysers for eight-hour sessions three times weekly, with a mean weekly Kt/V reported near 1.67. Almost all patients achieved normal blood pressure without antihypertensive medicines, and morbidity and mortality were reported to be markedly lower than in many other units.

More frequent haemodialysis—either long nocturnal treatment or short daily sessions—can also improve blood-pressure control and symptoms and may improve quality of life, although benefits and burdens depend on the regimen and the individual patient.

Frequency of measurement

The source recommends assessing dialysis dose every three months in stable patients and at least monthly in unstable patients. Formal UKM is described as the preferred routine approach, with URR and Kt/V available as additional practical measures.

URR

The minimum target cited from UK guidance is a URR above 65%, which in practice requires aiming for approximately 70% so the minimum is met reliably.

An individual URR can be related only approximately to Kt/V. One study reported that a URR near 60% corresponded to a mean Kt/V of 1.12, with values ranging from approximately 1.0 to 1.3.

nPCR

The source gives an nPCR target of 1.0 g/kg/day. Increasing Kt/V is often associated with an increase in calculated nPCR, but nutritional interpretation requires clinical context.

Why the delivered dialysis dose may be lower than expected

Common causes include:

• A lower actual blood-flow rate than the rate prescribed or displayed.

• Loss of treatment time because the patient arrives late, dialysis starts late, the session ends early at the patient’s request or for a medical reason, cannulation is difficult, or machine alarms repeatedly interrupt treatment.

• Access recirculation.

• Dialyser clotting and formation of small thrombi.

• Technical errors in collection of pre- or post-dialysis blood samples.

• Greater sequestration of urea in peripheral tissues, particularly muscle; this is influenced partly by cardiac output and tissue perfusion.

Increasing the dialysis dose

The delivered dose can be increased by changing dialyser surface area, blood-flow rate, or treatment time.

• Blood flow: achievable flow is often limited by the quality of the vascular access—a graft, fistula, or catheter. Nevertheless, patients and staff may underestimate the improvement that is possible before a higher flow is tested carefully.

Increasing blood flow beyond the capacity of the access can partially collapse the arterial blood line, produce more machine alarms, and interrupt dialysis. A larger-bore needle may improve flow and help achieve the highest safe rate supported by the access.

• Dialyser size: increasing dialyser surface area usually produces only a modest rise in the delivered dialysis dose.

• Dialysate flow: increasing dialysate flow from 500 to 800 mL/min can increase effective KoA by about 15%. With modern dialysers, however, this has often produced little additional Kt/V in practice.

• Dialyser performance: changing the dialyser can raise the delivered dose, but a high-efficiency dialyser adds little if blood flow is severely limited by poor vascular access. A dialyser with a higher KoA can provide greater small-solute clearance when the remaining parts of the system are not limiting.

• Treatment time: increasing time is the most dependable way to increase the dialysis dose.

A longer session increases removal of urea and larger molecules and allows more complete equilibration between body compartments, thereby increasing total-body urea reduction. Patients may find longer sessions burdensome, and additional time increases treatment costs.

Patients, staff, and healthcare providers all need clear education about the importance of completing the prescribed treatment.

Changing from conventional haemodialysis to a convective treatment such as haemofiltration or haemodiafiltration can increase removal of selected larger middle molecules.