Discordance between Iothalamate and Iohexol Urinary Clearances

Background Iothalamate and iohexol are contrast agents that have supplanted inulin for the measurement of glomerular filtration rate (GFR) in clinical practice. Previous studies have noted possible differences in renal handling of these 2 agents, but clarity about the differences has been lacking. Study Design Study of diagnostic test accuracy. Setting & Participants 150 participants with a wide range of GFRs were studied in an outpatient clinical laboratory facility. Index Tests Simultaneous urinary clearances of iothalamate, iohexol, and creatinine. Reference Test None. Outcome Relative differences between the urinary clearances. Iohexol and iothalamate in plasma and urine were assayed concurrently by a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Results Mean iohexol, iothalamate, and creatinine clearances were 52 ± 28 (SD), 60 ± 34, and 74 ± 40 mL/min/1.73 m², respectively. The proportional bias of iohexol to iothalamate urinary clearance was 0.85 (95% CI, 0.83-0.88) and was proportional across the GFR range. The mean proportional bias of iohexol clearance compared with creatinine clearance is 1.27 (95% CI, 1.20-1.34), whereas that of iothalamate clearance compared with creatinine clearance is 1.09 (95% CI, 1.03-1.15). Limitations Lack of reference standard. Conclusions This study reveals a significant and consistent difference between urinary clearances of iothalamate and iohexol. Comparison of studies reporting renal clearance measurements using iohexol versus iothalamate must account for this observed bias.