Compensatory biliary and urinary excretion of gadobenate ion after administration of gadobenate dimeglumine (MultiHance(®)) in cases of impaired hepatic or renal function: a mechanism that may aid in the prevention of nephrogenic systemic fibrosis?

Abstract

Objective: To determine whether increased elimination of gadobenate ion via the hepatobiliary pathway might compensate for reduced/absent elimination via the urinary pathway in the event of compromised renal function, as a possible protective mechanism against nephrogenic systemic fibrosis (NSF).

Methods: 15 male Crl:CD(®) R(SD)Br rats (Charles River Italia, Como, Italy) randomized to three treatment groups: (1) animals with occluded bile ducts, (2) animals with occluded renal vessels and (3) control animals, each received 0.25 mmol kg(-1) of bodyweight of gadobenate dimeglumine (MultiHance(®); Bracco Imaging SpA, Milan, Italy). Urine and bile were collected from 0-30, 30-60, 60-120, 120-240 and 240-480 min after gadobenate dimeglumine administration prior to exsanguination. Determinations of gadobenate ion in blood, bile and urine were performed by high-performance liquid chromatography. Gadolinium (Gd(3+)) levels in excised liver and kidneys were determined by X-ray fluorescence.

Results: The recovery of gadobenate ion in the urine of rats with bile duct occlusion was significantly higher than that in the urine of normal rats (89.1 ± 4.2% vs 60.6 ± 2.8%; p < 0.0001). Conversely, mean recovery in the bile of rats with renal vessel occlusion was significantly higher than that in the bile of normal rats (96.16 ± 0.55% vs 33.5 ± 4.7%; p < 0.0001). Gadobenate ion was not quantifiable in any group 8 h post-injection.

Conclusion: Compensatory elimination may be an effective means to overcome compromised renal or hepatobiliary elimination.

Advances in knowledge: The absence of NSF in at-risk patients administered with gadobenate dimeglumine may in part reflect greater Gd(3+) elimination via the hepatobiliary route.

Figure 1.

Cumulative urinary (a) and biliary (b) excretion of gadobenate²⁻ (percentage of injected dose) after intravenous injection of 0.25 mmol kg⁻¹ gadobenate dimeglumine to rats (n = 5 per group) with bile duct occlusion (a) or urinary vessel occlusion (b).

Figure 2.

Residual gadolinium (Gd³⁺) levels in liver and kidney at 8 h post-injection of 0.25 mmol kg⁻¹ gadobenate dimeglumine to normal rats and to rats with bile duct occlusion or urinary vessel occlusion (n = 5 per group). The residual Gd³⁺ levels after 8 h accounted for <0.6% of the injected dose in all groups and were similar across groups (see inset).