RESUMO
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.
RESUMO
The purpose of this study was to validate serum creatinine (SCr) concentrations assayed in the Central Biochemistry Laboratory of the National Institutes of Health (NIH)-funded Chronic Kidney Disease in Children (CKiD) study utilizing an enzymatic assay (Siemens Advia 2400) against a method traceable to reference isotope dilution mass spectroscopy (IDMS) developed by the National Institute of Standards and Technology (NIST). High-performance liquid chromatography (HPLC) measured SCr after external validation utilizing IDMS-based standard reference materials. Sera from the first 201 subjects enrolled in CKiD were analyzed and compared for creatinine concentration by enzymatic and HPLC methods. Fifty "normal" pediatric sera were subsequently analyzed. Finally, a "pediatric" reference standard was prepared and examined for accuracy and precision. Enzymatic SCr concentrations (median 1.4 mg/dl) of CKiD subjects were well correlated with HPLC (r = 0.984) but were slightly higher (+7%; p < 0.001). Agreement was poorer at lower SCr (median 0.4 mg/dl) when using samples from normal children and the "pediatric" reference standard. However, the Roche enzymatic assay was comparable with HPLC in accuracy and precision. Referring physicians should be aware of the accuracy and reproducibility of their laboratory's SCr assay. Our enzymatic assay agreed well with HPLC in CKiD subjects with elevated SCr. We suggest that NIST develop a pediatric SCr standard reference material for use by assay manufacturers to improve accuracy and precision of assays at the low SCr levels observed in most pediatric patients.