A physiological model for iohexol plasma clearance supporting diagnostics of kidney function.

Area of Science:

• Biochemical Engineering
• Pharmacokinetics
• Renal Physiology

Background:

• Current methods for estimating Glomerular Filtration Rate (GFR) from plasma clearance have limitations.
• Accurate GFR estimation is crucial for clinical decision-making and drug dosing.

Purpose of the Study:

• To develop a physiologically based method for calculating plasma clearance of iohexol.
• To address shortcomings in existing GFR estimation techniques.

Main Methods:

• A mechanistic mass balance model was developed based on biochemical engineering principles.
• In- and outgoing molecular flows of iohexol between plasma and tissues were balanced over time.
• Plasma samples were collected post-intravenous iohexol injection until complete elimination.

Main Results:

• The mass balance model accurately predicted iohexol distribution and elimination kinetics.
• The model's iohexol clearance calculations were validated against established methods.
• Accurate clearance was estimated in ten healthy subjects using the mass balance model.

Conclusions:

• The physiologically based mass balance model provides a more accurate in vivo clearance estimation compared to traditional methods.
• This model, validated with iohexol, is potentially applicable to other renal clearance markers.
• The mechanistic approach enhances the reliability of clearance measurements.