Multicenter Laboratory Comparison of Iohexol Measurement

Abstract

Background: Iohexol is utilized for measurement of kidney glomerular filtration rate (GFR). Until recently, there have not been available proficiency standards to assist in calibrating a laboratory's results. In view of a shift in calibration at the University of Rochester Medical Center (URMC) laboratory, serving as Central Biochemistry Laboratory for the CKiD study, we performed a multi-centered laboratory comparison.

Methods: Two batches of 30 fortified sera and patient samples from serum or heparinized plasma were sent for duplicate analysis to URMC, University of Minnesota (UMN), Mayo Clinic, and University of Lund. Five proficiency testing materials from Equalis AB were also provided. Iohexol calibration was performed using dilutions of Omnipaque™ 300 and concentrations measured by HPLC or LC-MS/MS (Mayo).

Results: UMN and Lund agreed well. URMC calibration was 11-13% lower, and Mayo was 4-8% lower for fortified samples. URMC corrected calibration was 3-8% higher for these samples. When measured values were adjusted for the results of the Equalis samples, all laboratories agreed within 1-2% on all iohexol concentrations.

Conclusions: For 12 URMC calibrator lots from 11/ 2006 to 3/ 2016, the factor quantifying the underestimation of measured to true iohexol concentration was 0.89. If each concentration were divided by 0.89, the calculated GFRs would be reduced by 10-11%. GFR results for CKiD were adjusted for this shift in calibration. Regular examination of iohexol proficiency testing materials, free exchange of samples among laboratories, and standardized dilution of the stock iohexol for calibration would help to bring more universal agreement to this assay.

Figures

1

Phase 1 comparison of measured vs. target values for iohexol in fortified samples. Plot symbols for the various matrices are as listed below the figure. The solid line is the mean difference for all samples and the dashed lines denote the 95 percentile limits of agreement for the mean values.

2

Median iohexol concentrations in 6 pooled patient samples included in Phase 1.

3

Phase 2 comparison of the median concentrations of 12 patient (light shade) and 3 pooled (dark shade) samples containing iohexol: A) left panel is plasma and right panel is serum samples. B) Same measurements shown in part A corrected using a factor derived from results for the Equalis EQA samples vs. the Equalis target values.

3

Phase 2 comparison of the median concentrations of 12 patient (light shade) and 3 pooled (dark shade) samples containing iohexol: A) left panel is plasma and right panel is serum samples. B) Same measurements shown in part A corrected using a factor derived from results for the Equalis EQA samples vs. the Equalis target values.

4

Difference between laboratory measured and target values for 5 Equalis EQA samples. The solid line is the mean value for the 5 samples and the dashed lines denote the 95 percentile limits of agreement for the mean values.

5

Calibration of CKiD iohexol concentrations after November 2006. A) Measured original concentrations (Y axis) vs. true concentrations determined from nominal concentrations of calibrators (X axis), showing a slope of 0.89 with no significant intercept. B) Residuals as a function of true concentrations, showing no significant differences from zero when 0.89 x true concentrations is subtracted from the measured iohexol concentrations.

5

Calibration of CKiD iohexol concentrations after November 2006. A) Measured original concentrations (Y axis) vs. true concentrations determined from nominal concentrations of calibrators (X axis), showing a slope of 0.89 with no significant intercept. B) Residuals as a function of true concentrations, showing no significant differences from zero when 0.89 x true concentrations is subtracted from the measured iohexol concentrations.