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What happens to dialyzer urea clearance (K) with changes in dialyzer size (KoA), Qb and Qd?

Interactive Diagram (playground)

Limitations of Kt/V

  • Kt/V overestimates dialysis adequacy in thin, malnourished patients and elderly females due to sarcopenia and a low ‘V’. This may lead to under-dosing of dialysis. Kt corrected for body surface area may be a more accurate measure of dialysis dose in these patients.
  • There is a high index of error related to inaccurate post-dialysis BUN measurement.
  • Single treatment may not represent other treatments ( missed or shortened)
  • spKt/V or eKt/V is not applicable to daily or nocturnal dialysis. It is useful only for conventional 3 times a week intermittent hemodialysis.
  • Kt/V is a marker only of urea clearance and not of other toxic/uremic solutes that exist.
  • Other uremic toxins such as phosphate, β2 microglobulin, guanidino compounds etc. do not follow the same hemodialysis kinetics as urea and therefore their clearances are not accurately reflected by Kt/Vurea.1
  • A high Kt/V(>1.4) has not been shown to predict better survival in any randomized controlled studies (e.g. HEMO study2).This implies that there are other determinants of poor survival in hemodialysis patients besides urea clearance and that despite a high dialysis urea clearance (Kt/V), patients may retain other toxic solutes that ultimately are equally or more important than urea in influencing prognosis on dialysis.3
  • Despite these controversies surrounding KT/Vurea, it remains the most frequently used parameter for determining dialysis adequacy and its routine monitoring may help to identify problems of dialysis delivery such as access recirculation etc.

Sources:

  1. Comparing the urea reduction ratio and the urea product as outcome-based measures of hemodialysis dose. AU Li Z, Lew NL, Lazarus JM, Lowrie EG SOAm J Kidney Dis. 2000;35(4):598.
  2. Eknoyan G, Beck, GJ Cheung AK, et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347:2010.
  3. Meyer TW,Sirich TL,Fong KD et al. Kt/Vurea and non urea small solute levels in the hemodialysis study. JASN 2016;27:3469

Why Care About Kt/V?

  • Urea is considered a surrogate to other small molecular weight uremic toxins and is easy to measure in the blood pre and post hemodialysis.
  • Although its use has limitations, it is an easily measured and useful marker of hemodialysis adequacy.
  • Kt/Vurea has helped standardize dialysis dosage based on urea clearance. It provides a tool to avoid grossly inadequate dialysis.
  • Its routine monitoring may help to identify problems of dialysis delivery such as access recirculation. 
  • Urea reduction ratio (URR= 1-postdialysis BUN/predialysis BUN) is a less optimal measure of dialysis adequacy as it does not account for ultrafiltration during dialysis and assumes that V is constant during dialysis.

How to Measure Kt/V?

Daugirdas mathematical formula to calculate:
Kt/V  = -ln (R – 0.03) + [(4 – 3.5R) x (UF ÷ W)]

Where…
R= post HD BUN/preHD BUN
UF= UF volume in L
W=  post dialysis weight in kg

Online calculators and normograms are available to calculate Kt/V using formula above.

The quick and dirty method:

  • If the dialyzer’s clearance (K) is known (based on the packet insert provide by the manufacturer at a Qb of 400ml/min) and is 250 ml/min and the dialysis session time is 240 minutes (4 hours)
    • then Kt (dialysis dose)= 250 x 240 = 60,000ml or 60 liters
  • If the patient weighs 70kg. His TBW is 60% of 70kg
    • then V = 70 kg multiplied by .60 = 42 liters
  • So the ratio – K multiplied by t to V, or Kt/V  compares the amount of water that passes through the dialyzer and is cleared of urea to the amount of water in the patient’s body.
    • KT/V for this patient will be= 60/42 = 1.42

Caveat: If this same patient has 3 kg of  edema fluid (EDW of 70kg)  then V = 60% (70kg)+ 100%(3kg)= 45L and not 42L. This is because edema fluid adds to the TBW in its entirety as urea distributes evenly across body water.

What is Kt/Vurea?

Human Kidney vs Dialyzers

Human Kidney VS Dialyzers

High efficiency dialyzers have a urea clearance (K) of >200ml/min (as long as blood flow and dialysate flow are not limiting) but this decreases significantly with solutes of middle and high molecular weights such as β2 microglobulin (11,800 Da).

Dialyzers that are high flux (and typically also high efficiency - high Kuf and KoA) have high small solute (urea) clearance and high middle molecule clearance.

Normal kidneys have a urea clearance (K) of around 125ml/min stable across various molecular weights up to 50,000-60,000 daltons. Therefore human kidneys are high flux!

High Efficiency vs
High Flux

High Efficiency

High Flux

 Membrane Characteristics

  •  Numerous pores, thin membrane, and high surface area allowing high small molecule (urea) clearance
  • Larger pores allowing better middle molecule (β2 microglobulin) clearance

 General Characteristics

(high diffusive clearance)

  • Dialyzer urea clearance rate (K) is usually >210 mL/min
  • High KoA (determines ‘efficiency’) – KoA urea of the dialyzer is usually > 800-1000 mL/min. Remember that the in vitro KoA provided by the manufacturer is often 20% higher than in vivo values.
  • Kuf is variable
  • Clearance of middle molecular weight molecules (β2 microglobulin) is variable
(high convective clearance)

  • Kuf (determines ‘flux’) of dialyzer is high (>15-20ml/h/mm Hg)
  • Clearance of middle molecules (β2 microglobulin ) is high (>20ml/min)

Technical Requirements

  • Dialyzer with a high KoA (>800-1000ml/min)
  • High blood flow (≥350 mL/min)
  • High dialysate flow (≥500 mL/min)
  • Bicarbonate dialysate (it is important to use  Bicarbonate-containing dialysate to avoid symptoms associated with acetate intolerance (i.e., nausea, vomiting, headache, hypotension, worsening of metabolic acidosis, and cardiac arrhythmia)
  • Dialyzer with a high Kuf
  • Ultrapure water for dialysis
  • Automated ultrafiltration control is necessary to avoid errors in TMP calculation that can result in massive flux of water across a high flux membrane and hemodynamic instability

More on High Flux Dialysis

  • HEMO study1 did not show a mortality benefit between high flux and low flux dialysis.
  • However, the HEMO study, MPO2 trial, and EGE3 trial showed a survival benefit (especially cardiovascular) in subset of patients with albumin≤4mg/dl, dialysis vintage ≥3.7 years, diabetes or those with an AV fistula.
  • KDOQI Adequacy Work group recommends use of high flux dialyzers routinely as long as appropriate water treatment is available.

Sources:

  1. Eknoyan G, Beck, GJ Cheung AK, et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347:2010. Hemodialysis study(HEMO)
  2. Locatelli, martin-Malo, Hannedouche et al. Membrane permeability Outcome (MPO) study group. Effect of membrane permeability on survival of hemodialysis patients. JASN 2009;20(3):645
  3. Asci, Tz, Ozkahya et al. EGE study group. The impact of Membrane permeability and dialysate purity on cardiovascular outcomes.JASN 2013 May;24(6):1014-23 

Transmembrane Pressure

CLINICAL PEARL:

In modern dialyzers with volumetric control of ultrafiltration, TMP’s primary role is to help monitor filter function:
↓    A drop in TMP could be due to a leak or filter rupture
↑    A rise in TMP could be due to filter clotting

Convection

CLINICAL PEARLS:

  • During conventional intermittent hemodialysis, urea is cleared mostly by diffusion. However, convection contributes in small amounts to urea clearance. Higher the ultrafiltration during a given treatment, more the convective clearance of urea.
  • With the use of high flux dialyzers in the current era and better middle molecule clearance, the risk of β2 microglobulin associated amyloidosis in hemodialysis patients is becoming a rarer entity.

Diffusion

CLINICAL PEARLS:

  • During conventional intermittent hemodialysis, urea is mostly cleared by diffusion given its small solute size and high concentration gradient between blood and dialysate.
  • Drugs that have a molecular weight of <1000 Da have high water solubility and low protein binding in plasma are cleared well with hemodialysis. Lithium is one such drug. Hemodialysis is the treatment of choice for severe lithium toxicity.