Discordance Between Iothalamate and Iohexol Urinary Clearances

Seegmiller, Jesse C.; Burns, Bradley E.; Schinstock, Carrie A.; Lieske, John C.; Larson, Timothy S.

doi:10.1053/j.ajkd.2015.08.020

Cited by 55 publications

(41 citation statements)

References 15 publications

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“…FGF23 was determined 3-6 months after baseline GFR was measured; however, GFR is predicted to decline by ,1 ml/min per 1.73 m 2 over this period (47). GFR determined by iohexol clearance might underestimate GFR as determined by inulin clearance (48,49). Such underestimation should not bias our results as we defined progression as dialysis, transplantation, or a within-person decrease of 50% in GFR rather than an absolute value of GFR.…”

Section: Discussionmentioning

confidence: 96%

Fibroblast Growth Factor 23 and Risk of CKD Progression in Children

Portale

Wolf

Messinger

et al. 2016

CJASN

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Section: Discussionmentioning

confidence: 96%

Fibroblast Growth Factor 23 and Risk of CKD Progression in Children

Portale

Wolf

Messinger

et al. 2016

CJASN

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“…Net secretion represents on average 9% of creatinine renal excretion clearance (CL R ) based on inulin as a GFR marker in subjects with normal renal function, although this contribution varies widely (2–15%) between studies 8 . Data based on iothalamate and iohexol as alternative GFR markers suggest up to 24% and 38% contribution of active secretion to creatinine clearance, respectively 9 . Current in vitro data on creatinine specificity for renal transporters are inconsistent, with involvement of organic cation transporter 2 (OCT2) and organic anion transporter 2 (OAT2) indicated on the basolateral membrane, and multidrug and toxin extrusion (MATE)1 and MATE2‐K transporters, on the apical (luminal facing) membrane of the proximal tubule cells ( Table ).…”

Section: Figurementioning

confidence: 99%

Mechanistic Models as Framework for Understanding Biomarker Disposition: Prediction of Creatinine‐Drug Interactions

Scotcher

Arya

Yang

et al. 2020

CPT Pharmacom & Syst Pharma

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Creatinine is widely used as a biomarker of glomerular filtration, and, hence, renal function. However, transporter-mediated secretion also contributes to its renal clearance, albeit to a lesser degree. Inhibition of these transporters causes transient serum creatinine elevation, which can be mistaken as impaired renal function. The current study developed mechanistic models of creatinine kinetics within physiologically based framework accounting for multiple transporters involved in creatinine renal elimination, assuming either unidirectional or bidirectional-OCT2 transport (driven by electrochemical gradient). Robustness of creatinine models was assessed by predicting creatinine-drug interactions with 10 perpetrators; performance evaluation accounted for 5% intra-individual variability in serum creatinine. Models showed comparable predictive performances of the maximum steady-state effect regardless of OCT2 directionality assumptions. However, only the bidirectional-OCT2 model successfully predicted the minimal effect of ranitidine. The dynamic nature of models provides clear advantage to static approaches and most advanced framework for evaluating interplay between multiple processes in creatinine renal disposition.

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“…Three laboratories (Lund, UMN, and URMC) used HPLC, with the URMC laboratory making measurements with 2 different sets of calibrator values (preSep2014 and postSep2014). Mayo Clinic used LC-MS/MS (13). Initial measurement procedures in samples were developed using HPLC (10,11,14,15).…”

Section: Laboratories and Samplesmentioning

confidence: 99%

Multicenter Laboratory Comparison of Iohexol Measurement

Schwartz

Wang

Erway³

et al. 2018

The Journal of Applied Laboratory Medicine

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Background: Iohexol is used 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 multicentered 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 TM 300 and concentrations measured by HPLC or LC-MS/MS (Mayo). Results: The 2 batches sent to UMN and University of 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 November 2006 to March 2016, the factor quantifying the underestimation of measured to true iohexol concentration was 0.89. If each concentration was 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. Laboratories; 4 EQUALIS;

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Discordance Between Iothalamate and Iohexol Urinary Clearances

Cited by 55 publications

References 15 publications

Fibroblast Growth Factor 23 and Risk of CKD Progression in Children

Fibroblast Growth Factor 23 and Risk of CKD Progression in Children

Mechanistic Models as Framework for Understanding Biomarker Disposition: Prediction of Creatinine‐Drug Interactions

Multicenter Laboratory Comparison of Iohexol Measurement

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