Hemodialysis (HD): prescribing

Blood flow rate (Q_B) and dialysate rate (Q_D)

Blood flow (Q_B): 3-5 mL/kg/min

• Max: 400 mL/min for Gambro Phoenix machine

Dialysate rate (Q_D): 1.5-2x Q_B

• Min: 350 mL/min for Gambro Phoenix machine

Choosing a dialyzer

• Goal is to minimize the extracorporeal blood volume (ECV) while ensuring efficient dialysis
• As a rule of thumb, the dialyzer surface area should be roughly equal to the child’s BSA

Priming solution

Extracorporeal circuit volume

• The prime solution will depend on the extracorporeal blood volume of the circuit
• Total extracorporeal blood volume (ECV) = lines (tubing) + dialyzer priming volume
  note

  Unlike with

  CKRT

  , the priming volumes for

  HD

  dialyzers do not include the tubing needed to connect to the patient

• Available tubing will vary by institution but generally come in a few different sizes:
  • Neonatal (<12 kg), pediatric (12-30 kg), and adult (>30 kg)
    • At LPCH, the line volumes are as follows:
      • Neonatal: 44 mL
      • Pediatric: 73 mL
      • Adult: 103 mL

Priming solution

• Options include: blood, albumin, or normal saline (NS)
• Blood prime: used if extracorporeal blood volume (ECV) >10% of estimated blood volume (EBV)
  • See: kidney.wiki blood & plasma volume calculator
    • For infants, EBV ≈ 80 mL/kg
    • For older children, EBV ≈ 70 mL/kg
  • As a general rule, usually use blood prime if <10 kg
  • For blood prime, we mix 140 mL of Adsol-preserved PRBCs (Hct ~55%) with 100 mL of albumin to bring Hct close to physiologic (~32%)
• NS prime: used if ECV ≤10% of EBV and hemodynamically stable
• Albumin prime: used if ECV ≤10% of EBV but hemodynamically unstable
  • Albumin does contain aluminum, so if being used long-term can result in aluminum accumulation (evaluated every 6 months)

Return prime?

• This occurs at dialysis initiation; not to be confused with rinse back, which occurs at dialysis termination
• When the patient is connected and their blood enters into the circuit the priming solution that is in the machine will either be given back to the patient (i.e., the prime is “returned”) or will be wasted (i.e., not returned)
  • If the prime is not returned, the extracorporeal blood volume has been removed from the patient and has not been replaced with anything, which results in a rapid intravascular volume deficit; this is often well tolerated in larger patients but can be an issue in smaller or hemodynamically unstable patients
• Therefore, the prime is returned in patients who are smaller (typically <18 kg) or if they are hemodynamically unstable

Rinse back?

• At the end of dialysis, the blood in the circuit can be wasted or can be infused (“rinsed back”) into the patient
• Typically, this is protocolized based on which prime was used:
  • If NS or albumin prime was used, rinse back the extracorporeal volume after the session
  • If blood prime was used, typically the extracorporeal volume is not rinsed back into the patient (i.e., it is wasted)
    • In some circumstances (e.g., significant anemia), one can remove extra UF in anticipation of rinsing back some or all of the extracorporeal blood volume
      • The hematocrit of the blood in the circuit is the same as the hematocrit in the patient, so infusing this blood back into the patient will not raise their hematocrit unless extra
        ultrafiltrate
        is removed in anticipation of the rinse back procedure
      • The volume rinsed back can be imprecise
      • Caution must be used to avoid unwanted fluid shifts or excessive hemoconcentration

Dialysate electrolyte composition

• Sodium 138-140 mEq/L
  • Possible range (for dysnatremias): 130-150 mEq/L
• Calcium 2.5, 3.0, or 3.5 mEq/L
  • Usually 2.5-3.0 mEq/L per KDIGO, but may target higher end if hypocalcemic
• Bicarbonate 35-40 mEq/L
  • Target lower end unless significantly acidotic
• Potassium: determined by a sliding scale based on patient’s immediate predialysis potassium level
  • Alternatively, can use “Rule of 7”: patient’s K + dialysate K = 7 mEq/L
  • Can adjust sliding scale if needing to maintain K at a certain minimum (e.g., for cardiac reasons)
    example

    Potassium sliding scale (LPCH):
    

    K >6 mEq/L: use 1 mEq/L
    K 5.4-6.0 mEq/L: use 1 mEq/L
    K 4.1-5.3 mEq/L: use 2 mEq/L
    K 3.1-4.0 mEq/L: use 3 mEq/L
    K ≤3.0: use 4 mEq/L

Anticoagulation

Heparin anticoagulation

• Usually start with 10 U/kg load (only if needed) followed by 10 U/kg continuous infusion, and titrate based on ACT monitoring
  • In patients with bleeding concerns, may start with 5 U/kg load and 5 U/kg continuous
  • Before adjusting heparin dose, consider anticoagulation monitoring levels, clot burden and access/filter pressures
• Activated clotting time (ACT): how long it takes for the blood to clot in the presence of heparin
  • High ACT levels may be increased in patients on warfarin, with liver disease, clotting factor deficiency, or lupus anticoagulants
  • Goal: typically 120-150 seconds
    • The goal may be raised until adequate anticoagulation is achieved (typically 150-180 seconds, but may be 170-200 seconds), and/or if patients are at high risk for clotting or serious sequelae from thromboses (e.g., dialysis catheter terminates in a Fontan)
    • An ACT level is checked prior to initiation of dialysis and then every hour while on dialysis
      • If the ACT level is in the goal range prior to dialysis initiation, no loading dose should be given
    • Some centers prefer to titrate based on activated partial thromboplastin times (aPTTs) or anti-Xa (heparin activity) levels

Heparin-free dialysis

• Indications: thrombocytopenia (Plt <50k), evidence of active bleeding, recent surgery, systemic anticoagulation, coagulation factor deficiency
• Requires frequent flushing with saline: usually start with every 15 minutes, and back off to every 30 minutes

Dialysis duration, ultrafiltration volume

Calculating time on dialysis

• Time will depend on if this is maintenance hemodialysis or if we are just starting out dialyzing for the first time
  • To avoid disequilibrium syndrome, we usually start out with a urea reduction ratio (URR) of 30% for the first day, 50% for the second day, and 70% for the third day (and keep at 70% thereafter)
• Take the equation Kt/V = -ln(C_t/C₀), where
  • K = urea clearance of dialyzer
    • As a shorthand estimate, this is roughly equal to the rate that blood passes through the dialyzer (i.e., the blood flow rate, or Q_B)
  • t = time of dialysis session (in minutes)
  • V = volume of distribution of urea (in mL)
    • Roughly equal to the total body water (TBW)
    • See: kidney.wiki BSA & total body water calculator
      • A crude estimate for TBW is 600 mL/kg of body weight
      • Morgenstern equation is a more accurate estimation of TBW in children [PMID 16319190, PMID 26754039]
        • Boys: 0.1 * (Height in cm * Weight in kg)^0.68 - (0.37 * Weight in kg)
        • Girls: 0.14 * (Height in cm * Weight in kg)^0.64 - (0.35 * Weight in kg)
        • Output is expressed in L; simply multiply by 1,000 to get the TBW in mL
      • If fluid overloaded: fluid distributes evenly across body water, so if a patient has significant fluid overload, their edema fluid (1000 mL/kg of weight attributed to fluid overload) should be added to the TBW calculated from their estimated dry weight
        example

        A 150 cm, 55 kg boy is estimated to have 10% fluid overload (estimated dry weight of 50 kg)

        • TBW = 5 L (fluid overload weight) + 0.1*(150 cm * 50 kg)^0.68 - (0.37*50 kg) = 5 L + 24.7 L = 29.7 L
        • Compare this with the TBW if fluid overload was ignored and a body weight of 55 kg was used in the Morgenstern equation: 25.7 L (a difference of >13%)

  • C = concentration of urea
    • C_t = BUN concentration at the end of dialysis (time t)
    • C₀ = BUN concentration at the start of dialysis (time 0)
    • Thus, C_t/C₀ = the amount of urea remaining, or the inverse of the urea reduction ratio (URR)
    • For a URR of 0.7
      • Modify the equation to solve for t (time): t = -ln(C_t/C₀)*V/K
        • To achieve a URR of:
          • 30%: t = -ln(0.7)*V/K
          • 50%: t = -ln(0.5)*V/K
          • 70%: t = -ln(0.3)*V/K

Total ultrafiltration (UF)

• Depends on the difference between today’s pre-dialysis weight and the patient’s dry weight
  • Max fluid removal of 10-13 mL/kg/h (or 5% of body weight [BW] per session)

Pure ultrafiltration (PUF)

• Removal of fluid without dialysate running (i.e., no diffusion)
• Occasionally will add 30 or 60 minutes of PUF added onto end of dialysis session to pull off additional fluid
• Usually PUF is not needed and can instead simply extend the time on dialysis and achieve improved clearance in addition to the fluid removal

Dialysate temperature

• Usually set at 36.5°C
  • Can use lower temps (36.0°C) if wanting to pull more fluid, but this can make patients very uncomfortable

Medications

• E.g., Calcitriol, Zemplar, Epogen, Aranesp, Venofer, Mannitol
• Can choose to order with each dialysis session, or have ordered on the MAR (e.g., qMWF, qTuThSa, or weekly)
• If ordering on the MAR (rather than reordering every session):
  • Helps to put “with dialysis” and/or “by dialysis nurse” in the medication comments to avoid administration outside of dialysis setting
  • Make sure you document in the note/handoff that this is on the MAR so that others do not order extra doses by mistake

Labs

• Every time: potassium, PRN CBC w/ differential, PRN blood culture
  • iStat potassium will determine dialysate composition (based on sliding scale)
    • Per protocol, this is done with every dialysis start regardless if they have morning labs
• Before first session: must have hepatitis B surface antigen and anti-HbS or HbSAb (hepatitis B surface antibody)
• Pre- and post-BUN once weekly to calculate urea reduction ratio (URR)

Deaccessing

Catheter locks

• If a catheter is used rather than a fistula, lock the catheter with alteplase (tPA) after each session
  • Some centers will use heparin for locking the catheter
• Use 100% of the catheter lumen volume
  • If the catheter has had issues with clot buildup, infuse 110% of the catheter lumen volume
    • Catheter volumes usually listed in the catheter information in the EHR (e.g., under “LDAs” tab in Chart Review on Epic)
  • Otherwise, can find this information on the catheters themselves (e.g., on the red and blue clamps)
    • May be different for venous and arterial lumens

Assessing dialysis adequacy: Kt/V_urea

• Urea is used as a surrogate marker for other “uremic toxins”
  • Uremic toxins are metabolic waste products in the body that buildup in the setting of impaired kidney function
• Assessing urea clearance is the preferred method to assess hemodialysis dose and adequacy

Defining Kt/V

• Kt/V_urea is the clearance (K) multiplied by time (t) and divided by the volume of distribution of urea (V_urea)
  • Because its units cancel, Kt/V is sometimes described as a “dimensionless” ratio
    • Dialyzer clearance of urea (K) is expressed in volume of blood water per unit time (mL/min)
      • The volume of blood water that can be cleared of urea in 1 minute
      • Affected by Q_B, Q_D, K₀A, dialyzer surface area
    • t (time on dialysis) is expressed in minutes (min)
    • V_urea is a volume expressed in mL
  • K*t is, therefore, a multiple of the volume of blood water cleared of urea in a dialysis session; this is the dialysis dose
  • V_urea is the volume of distribution of urea in mL
    • V_urea = the total body water (TBW) corrected for the
      ultrafiltration
      volume that is lost during treatment, expressed in mL
      • Affected primarily by the patient’s estimated dry weight, but the
        ultrafiltration
        volume (UF) has a small effect
        • A large UF can raise the Kt/V by as much as 0.2, as it adds to the convective clearance of urea
  • When Kt/V = 1, this means that a volume of blood has been cleared that is equal to the distribution volume of urea
• Kt/V is monitored at least monthly

Why monitor Kt/V?

• Routine monitoring is necessary because the delivered Kt/V is often lower than the prescribed Kt/V, so monitoring is helpful to avoid underdialysis
  • Less than adequate dialysis is associated with poor outcomes
• In vitro K₀A overestimates in vivo measurements by 20-30%
• The prescribed Q_B and Q_D may not reflect what the patient actually receives (e.g., calibration errors, interruptions in treatment, access recirculation)

How is Kt/V calculated?

• Pre-dialysis BUN is drawn after the catheter/AVF is accessed but before the hemodialysis treatment is started
  • Collect the sample before injecting heparin, saline, or anything else that may dilute the sample
• At the end of dialysis, the UF rate is set to 0 mL/h and the blood flow rate (Q_B) is slowed to ≤100 mL/min for 15 seconds
  • Alternatively: set the UF rate to 0 mL/h and set the dialysate rate (Q_D) 0 mL/min for 3 minutes, without adjusting the blood flow rate (Q_B)
• The blood pump is stopped and the post-dialysis BUN is drawn from the arterial tubing (i.e., the side drawing blood from the patient, prefilter)
• Use the pre- and post-HD BUN measurements, treatment time, post-dialysis weight, and
  ultrafiltration
  volume to calculate Kt/V
  • Kt/V = -ln (URR–0.03) + [(4 – 3.5*URR) x (UF ÷ Weight)]
    • URR = C_t/C₀
      • Expressed as a percentage, URR = 1 - (C_t/C₀) * 100%
      • C_t = post-HD BUN
      • C₀ = pre-HD BUN
    • UF =
      ultrafiltration
      volume in liters (L)
    • Weight = post-dialysis weight in kilograms (kg)
    • Online Daugirdas II calculator: [Omnicalculator]
  • This (Daugirdas II) formula calculates is the “non-equilibrated” or “single pool” Kt/V (i.e., spKt/V)
  • Termed “non-equilibrated” because the BUN has not had time to equilibrate
    • Urea rebounds post-dialysis and reaches steady state (i.e., equilibrates) 30-60 minutes after dialysis
      • A post-dialysis BUN drawn 30-60 mins after dialysis is more accurate
    • A Kt/V calculated using a post-dialysis BUN drawn at this time is termed the “equilibrated” Kt/V (eKt/V)
      • eKT/V accounts for double pool kinetics
      • eKt/V tends to be about 0.15-0.2 units lower than spKt/V, depending on the rate of dialysis

What is “adequate?”

• A spKt/V is considered adequate if >1.2, but we target >1.4 to avoid underdialysis [KDIGO])
  • A target of >1.6 may be beneficial in children <12 years of age [PMID 33651178]
  • If equilibrated Kt/V is used, a target eKt/V >1.2 is recommended
• What about residual kidney function (RKF)?
  • If patients have significant residual native kidney urea clearance (Kru), the dose of HD may be reduced provided the Kru is measured periodically (typically every 3 months)
    • That being said, we don’t often do 24 hour urine collections on HD patients to factor in residual clearance to the Kt/V

Limitations of Kt/V

• Overestimates dialysis adequacy in malnourished patients due to sarcopenia (low urea generation) and a low volume of distribution of urea
• Post-dialysis BUN measurements can be highly variable depending on nutrition, catabolic state, and specimen collection technique
• Kt/V only measures urea, which is an imperfect surrogate for other uremic toxins that do not necessarily share the same kinetics (e.g., phosphate, β2 microglobulin)
• Only captures the effects of a single treatment, one which may or may not reflect the “typical” delivered dialysis dose for that patient
• spKt/V (or eKt/V) is only applicable for conventional, thrice weekly (3x/week) dialysis; it does not apply to alternative dialysis frequencies (e.g., 4x/week, or nightly HD)
  • Must instead use stdKt/V
• More is not necessarily better; higher Kt/V (e.g., >1.4 in the HEMO study) hasn’t been shown to predict better survival
• It does not take into account any quality of life measures; a patient with a Kt/V ≥1.2 who is fatigued, pruritic, and fluid overloaded is considered to have “adequate” dialysis whereas a patient with a Kt/V of 1.15 who is happy, energetic, and able to participate in activities is considered to have “inadequate” dialysis

Kt/V for dialysis schedules other than thrice weekly

• A single pool Kt/V (spKt/V) is calculated for a given session and standardized to the stdKt/V
• The target stdKt/V is >2.3, with a minimum delivered dose of >2.1 [KDIGO]
• stdKt/V is a weekly expression (normalized to V) of a modified equivalent urea clearance
  • Defined as the urea generation rate divided by the average predialysis (i.e., peak) BUN level
  • By definition, it includes the contributions of
    ultrafiltration
    during dialysis and Kru (residual renal clearance of urea)
  • Can be used to compare any dialysis modality, frequency, and duration