drug dosing in hemodialysis

Factors to Consider in Dosing for Kidney Disease/Dialysis

• Medication → How the drug is cleared (kidney vs liver), side effects, and if dose adjustment is needed

• Dialysis Procedure → Type of dialysis (hemodialysis, peritoneal), frequency, and how much drug is removed

• Patient → Age, weight, comorbidities, residual kidney function, and overall clinical condition

• Where to find info? → Drug references like Lexicomp, Micromedex, package inserts, and clinical guidelines

Clearance in Patients on Dialysis

• CL = total clearance of the drug

• CL_R = renal clearance (drug removed by the kidneys)

• CL_NR = non-renal clearance (drug removed by liver, lungs, etc.)

• CL_Dialysis = clearance provided by dialysis (artificial removal of drug from blood)

• CL=CL_R​+CL_NR​+CL_Dialysis​

Factors to consider when choosing a Dose for Patients on Dialysis

• Patient factors

  • Severity of illness

  • Type of infection

  • Patient size (weight, body composition)

  • Scheduling/timing of dialysis and hospital routines

• Dialysis factors

  • Dialysis filter type (affects how much drug is removed)

  • HD modality → how often and how long the dialysis sessions are

Dialysis Related Factors in Drug Dosing

• Filter

  • Different filters remove drugs at different rates (high-flux vs low-flux membranes)

• Schedule

  • When dialysis occurs (before/after dosing changes drug levels)

  • Frequency (e.g., 3 times/week vs daily dialysis)

  • Duration (longer sessions remove more drug)

• Adequacy

  • How effective the dialysis session is at clearing waste and drugs (depends on filter + schedule)

Different HD Filters 

• Conventional filters

  • Small pores → remove mainly small molecules

• High Efficiency filters

  • Large surface area (faster clearance)

  • Pores can be large or small

• High Flux filters

  • Large pores

  • Can remove middle molecules (size 500–15,000 Daltons) → things that conventional filters can’t clear

  • Can remove a lot of medication (best machine but not the best for when patient needs medications, cuz it removes that too)

Why does Filter Type Matters when taking Medication on a Dialysis

• Conventional Filter

  • Example) Vancomycin dose: 1000 mg every 7 days (Q7days)

  • Less drug removal → lower dose works

• High Flux Filter

  • Example) Removes vancomycin much more efficiently

  • Much higher doses required to keep drug at effective levels

Intermittent / Conventional Session

• 3–4 sessions per week

• Usually daytime

Frequent Session

• 5–7 sessions per week

• Can be daytime or nighttime (depends on session length)

Long Session 

• Each session lasts ≥5 hours

• Can be daytime or nighttime (depends on frequency & patient preference)

Blood Flow Rate (BFR)

• How fast blood is pumped from the patient into the dialysis machine

• Low BFR (<300 mL/min):

  • Blood moves through the filter more slowly

  • Less blood is cleaned per minute

  • Dialysis is less efficient → fewer toxins and fewer drugs are removed

Dialysate Flow Rate (DFR)

• How fast the dialysate (the cleansing fluid) flows through the machine

• Low DFR (<500 mL/min):

  • Less fresh dialysate passes through the filter

  • Creates less “driving force” to pull toxins and drugs out of the blood

  • Less drug clearance, so drug levels stay higher

High BFR/DFR

• More drug removed → may need higher or more frequent doses

Low BFR/DFR

• Less drug removed → smaller or less frequent doses may be enough, otherwise risk of toxicity

Medication Related Factors Affecting HD Drug Removal

• Molecular Weight / Size

  • Large molecules → harder to remove by dialysis

• Protein Binding

  • Drugs that are highly bound to proteins (like albumin) → less drug free in the blood to be filtered → not removed well

• Volume of Distribution (Vd)

  • Drugs with large Vd (spread out into tissues, fat, or cells) → less drug left in bloodstream to be dialyzed

• Water Solubility

  • Drugs that are not water-soluble → less likely to be removed

  • Water-soluble drugs stay in blood and dialysate can remove them more easily

Pharmacodynamic Properties

• Concentration-dependent killing

  • The drug works best when its peak concentration (Cmax) is very high compared to the bacteria

  • Higher dose → more effective killing

• Time-dependent killing

  • The drug works best when the drug level stays above the MIC (minimum inhibitory concentration) for a long time

  • Duration of exposure matters more than peak

Aminoglycosides are concentration-dependent killing or time-dependent killing?

• Concentration-dependent killing

Patient-Level Considerations in Hemodialysis

• Medication Regimen

  • Complex instructions and timing

  • Many medications (polypharmacy)

  • High risk of drug–drug interactions

• Adherence

  • Challenges with sticking to treatment, diet, and medication schedules

• Payment Issues

  • Cost concerns, especially with multiple dosages of the same drug

• Comorbid Illness

  • Other medical conditions complicate treatment (e.g., diabetes, hypertension, heart disease)