Gadolinium Concentrations in Biological Matrices From Patients Exposed to Gadolinium-Based Contrast Agents

Abstract

Objectives There is increasing evidence that Gd may be retained within the skin, bones, and solid organs in patients with normal renal function after exposure to Gd-based contrast agents (GBCAs). Here we present clinical data from 19 patients who requested referral to our clinical toxicology service for assessment of potential “Gd toxicity.” Materials and Methods Patients had undergone a median of 2 (interquartile range [IQR], 1–5) exposures to GBCAs and were reviewed at a median of 5 months (IQR, 2–8 months) after the last GBCA exposure. Patients had a clinical assessment by a clinical toxicologist, and biological samples were taken in 17 patients (89.5%). Gd concentrations were measured in these samples using inductively coupled plasma mass spectrometry. Results All patients had significant comorbidities, and after an extensive clinical review, none of the reported symptoms were considered likely to be related to “Gd toxicity.” Whole blood, plasma, and urine samples had detectable Gd concentrations in 69.2%, 78.6%, and 95.2% of samples, respectively. Median (IQR) concentrations of Gd were as follows: whole blood, 0.013 ng/mL (IQR, limit of detection [LOD]–0.884 ng/mL); plasma, 0.012 ng/mL (IQR, LOD–0.046 ng/mL); and spot urine, 0.304 μg/g creatinine (IQR, 0.070–3.702 μg/g creatinine). There were positive correlations between whole blood and plasma (P = 0.0024, r = 0.84), whole blood and urine (P = 0.0018, r = 0.82), and plasma and urine (P = 0.0001, r = 0.89) Gd concentrations. There was a negative correlation between Gd concentrations and the period after exposure for whole blood (P = 0.0028, r = −0.80), plasma (P = 0.0004, r = −0.86), and urine (P < 0.0001, r = −0.91). Conclusions We identified detectable Gd concentrations in biological matrices from all patients reporting exposure to GBCAs who were reviewed in our clinical toxicology outpatient clinic with concerns regarding potential “Gd toxicity”; however, there were no clinical features of toxicity present in this cohort. Further research is required to explore the pharmacokinetics and pharmacodynamics of GBCAs in patients with normal renal function and to determine the clinical significance of these detectable Gd concentrations.