Establishing Reference Intervals for Gadolinium Concentrations in Blood, Plasma, and Urine in Individuals Not Previously Exposed to Gadolinium-Based Contrast Agents

Abstract

Objectives 

Over the recent years, there have been increasing concerns that exposure to gadolinium-based contrast agents (GBCAs) may be associated with retention of Gd within the skin, bones, and solid organs in patients with normal renal function, although the clinical implications of this deposition remain to be established. There are no published data available to guide the development of reference intervals for Gd concentrations in biological samples from healthy people. The aims of this study were to (1) determine whether healthy individuals who have not received GBCAs have detectable concentrations of Gd in their blood and urine, and (2) to develop a reference range for Gd concentrations in blood and spot urine samples for healthy individuals.

Materials and Methods 

Whole blood, plasma, and spot urine samples were taken from 120 healthy volunteers with estimated glomerular filtration rate 70 mL/min per 1.73 m² or greater. Gd concentrations were measured in these samples using inductively coupled plasma mass–spectrometry. The reference intervals for Gd concentrations in whole blood, plasma, and urine were estimated as the 2.5th percentile and the upper reference limit as the 97.5th percentile.

Results 

Ten (8.33%) of the 120 subjects had detectable concentrations of Gd in their whole blood (n = 5) or spot urine (n = 5) samples; no subjects had detectable concentrations of Gd in their plasma samples. Our proposed reference intervals for Gd are as follows: whole blood, <0.008 ng/mL or <0.050 nmol/L; plasma, <0.009 ng/mL or <0.057 nmol/L; spot urine, <0.036 μg/g or <0.0250 nmol/mmol.

Conclusions 

The results of this study provide reference intervals for whole blood, plasma, and urine Gd concentrations in healthy subjects who have not previously received GBCAs and will assist clinicians in assessing patients who have concerns regarding potential Gd retention postexposure and help guide further clinical studies to explore the pharmacokinetics of GBCAs in patients with normal renal function.