Discordance Between Iothalamate and Iohexol Urinary Clearances

Area of Science:

• Nephrology
• Diagnostic Testing
• Pharmacokinetics

Background:

• Iothalamate and iohexol are widely used contrast agents for measuring glomerular filtration rate (GFR).
• Previous research suggested potential differences in the renal handling of iothalamate and iohexol, but these were not well-defined.

Purpose of the Study:

• To investigate and quantify the differences in renal handling and urinary clearance between iothalamate and iohexol.
• To assess the implications of these differences for GFR measurement accuracy.

Main Methods:

• A diagnostic test accuracy study involving 150 participants with diverse GFRs.
• Simultaneous measurement of urinary clearances for iothalamate, iohexol, and creatinine.
• Analysis of plasma and urine samples using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay.

Main Results:

• Mean clearances: iohexol (52±28 mL/min/1.73 m²), iothalamate (60±34 mL/min/1.73 m²), and creatinine (74±40 mL/min/1.73 m²).
• A significant proportional bias was observed: iohexol clearance was 0.85 times that of iothalamate clearance across the GFR range.
• Iohexol clearance showed a mean proportional bias of 1.27 compared to creatinine, while iothalamate showed 1.09.

Conclusions:

• A significant and consistent difference exists between the urinary clearances of iothalamate and iohexol.
• Studies comparing GFR measurements using iohexol versus iothalamate must account for this identified bias.
• The lack of a definitive reference standard for direct comparison remains a limitation.