Impact of Renal Impairment on Long-Term Retention of Gadolinium in the Rodent Skin Following the Administration of Gadolinium-Based Contrast Agents

Abstract

The results of this preclinical study support the use of 5/6-nephrectomized rats as a model for prolonged circulation time of GBCAs as seen in patients with severe renal impairment. Surgically induced severe renal impairment resulted in delayed clearance of the administered GBCAs in the study animals. The highest amount of Gd was observed in the skin after treatment with the nonionic linear GBCAs, whereas the lowest Gd values were observed after treatment with the macrocyclic agent. This suggests that the difference in the Gd values observed in rat skin tissue after treatment with the different GBCAs is caused of a different propensity of the different GBCAs to release Gd in vivo. However, the analytical method used does not distinguish between chelated and unchelated Gd.

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

“…These data suggest that a longer circulation time promotes Gd release (17). Following the administration of a macrocyclic GBCA, there were no significant differences in the long-term exposure of the skin to Gd between the renally impaired 5/6-nephrectomized and nonnephrectomized rats (17). This also supports the conclusion that a longer circulation time in the context of stable macrocyclic compounds does not lead to an increased Gd 3þ release in vivo.…”

“…Furthermore, they also showed a strong correlation between the GFR and the amount of residual Gd. These data suggest that a longer circulation time promotes Gd release (17). Following the administration of a macrocyclic GBCA, there were no significant differences in the long-term exposure of the skin to Gd between the renally impaired 5/6-nephrectomized and nonnephrectomized rats (17).…”

“…The longer GBCA circulation time also results in significantly higher Gd skin deposits in renally impaired 5/6-nephrectomized animals than in nonnephrectomized rats, which in turn leads to a higher exposure of the skin to Gd (17) (Fig. 4).…”

“…The role of the longer circulation time of GBCAs in ESRD patients on potential Gd release profiles can be simulated in rats with 5/6-nephrectomy. In these animals, one entire kidney and two-thirds of the second kidney are surgically removed, which leads to a reduced glomerular filtration rate (GFR) that in turn leads to a more than 3-fold increase in serum exposure to GBCAs as compared with nonnephrectomized rats (16,17,43).…”

“…The aim of this review is to summarize knowledge regarding the pathogenesis of NSF and the potential role of GBCAs in its pathology, with a focus on the animal experiments performed in our laboratory (11)(12)(13)(14)(15)(16)(17)(18). The potential role of complex stability of GCBAs will be highlighted by results from several in vitro and in vivo experiments in rodent models of NSF.…”