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Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: The purpose of this preclinical study was to investigate whether moderate chronic kidney disease is a factor in potentiating gadolinium (Gd) uptake in the brain.

Materials and methods: A comparative study was performed on renally impaired (subtotal nephrectomy) rats versus rats with normal renal function. The animals received 4 daily injections of 0.6 mmol Gd/kg a week for 5 weeks (cumulative dose of 12 mmol Gd/kg) of gadodiamide or saline solution. The MR signal enhancement in the deep cerebellar nuclei was monitored by weekly magnetic resonance imaging examinations. One week after the final injection, the total Gd concentration was determined by inductively coupled plasma mass spectrometry in different regions of the brain including the cerebellum, plasma, cerebrospinal fluid, parietal bone, and femur.

Results: After the administration of gadodiamide, the subtotal nephrectomy group presented a significantly higher T1 signal enhancement in the deep cerebellar nuclei and a major increase in the total Gd concentration in all the studied structures, compared with the normal renal function group receiving the same linear Gd-based contrast agent. Those potentiated animals also showed a pronounced hypersignal in the choroid plexus, still persistent 6 days after the last injection, whereas low concentration of Gd was found in the cerebrospinal fluid (<0.05 μmol/L) at this time point. Plasma Gd concentration was then around 1 μmol/L. Interestingly, plasma Gd was predominantly in a dissociated and soluble form (around 90% of total Gd). Total Gd concentrations in the brain, cerebellum, plasma, and bones correlated with creatinine clearance in both the gadodiamide-treated groups.

Conclusions: Renal insufficiency in rats potentiates Gd uptake in the cerebellum, brain, and bones.

No MeSH data available.


Protocol scheme of the study. SNx, subtotal nephrectomy of the 5/6 or sham operation; SNx 1 indicates first part of the surgery; SNx 2, second part of the surgery; CrCl, creatinine clearance. MRI was performed before the first injection, and then once a week (W). Twenty injections of gadodiamide, 0.6 mmol Gd/kg/injection, were distributed over 5 weeks, leading to a cumulative dose of 12 mmol Gd/kg. Killing was performed 6 days after the last injection.
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Figure 1: Protocol scheme of the study. SNx, subtotal nephrectomy of the 5/6 or sham operation; SNx 1 indicates first part of the surgery; SNx 2, second part of the surgery; CrCl, creatinine clearance. MRI was performed before the first injection, and then once a week (W). Twenty injections of gadodiamide, 0.6 mmol Gd/kg/injection, were distributed over 5 weeks, leading to a cumulative dose of 12 mmol Gd/kg. Killing was performed 6 days after the last injection.

Mentions: The general scheme of the protocol is illustrated in Figure 1. The study was carried out on SNx or sham female Sprague-Dawley rats (SPF/OFA female rats, Charles River, L'Arbresle, France) aged 10 weeks and weighing 232 ± 14 g for sham-operated rats and 217 ± 9 g for SNx rats at the beginning of the study. A subtotal nephrectomy (5/6 SNx) was performed at Charles River Laboratories: a first operation was performed when the rats were 6 weeks old to excise 1 kidney, and a second operation was performed 1 week later to remove the upper and lower poles of the remaining kidney. Similar surgery was performed at the same time in sham-operated control rats, but without kidney excision. After 1 week of recovery, and 1 additional week of acclimatization, the animals were randomized (n = 10/group). The rats were housed 2 per cage, at an ambient temperature of 22 ± 2°C, hygrometry of 45% ± 10%, in a room with 12/12 light/dark cycles. The animals had access to water and food ad libitum.


Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats
Protocol scheme of the study. SNx, subtotal nephrectomy of the 5/6 or sham operation; SNx 1 indicates first part of the surgery; SNx 2, second part of the surgery; CrCl, creatinine clearance. MRI was performed before the first injection, and then once a week (W). Twenty injections of gadodiamide, 0.6 mmol Gd/kg/injection, were distributed over 5 weeks, leading to a cumulative dose of 12 mmol Gd/kg. Killing was performed 6 days after the last injection.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383202&req=5

Figure 1: Protocol scheme of the study. SNx, subtotal nephrectomy of the 5/6 or sham operation; SNx 1 indicates first part of the surgery; SNx 2, second part of the surgery; CrCl, creatinine clearance. MRI was performed before the first injection, and then once a week (W). Twenty injections of gadodiamide, 0.6 mmol Gd/kg/injection, were distributed over 5 weeks, leading to a cumulative dose of 12 mmol Gd/kg. Killing was performed 6 days after the last injection.
Mentions: The general scheme of the protocol is illustrated in Figure 1. The study was carried out on SNx or sham female Sprague-Dawley rats (SPF/OFA female rats, Charles River, L'Arbresle, France) aged 10 weeks and weighing 232 ± 14 g for sham-operated rats and 217 ± 9 g for SNx rats at the beginning of the study. A subtotal nephrectomy (5/6 SNx) was performed at Charles River Laboratories: a first operation was performed when the rats were 6 weeks old to excise 1 kidney, and a second operation was performed 1 week later to remove the upper and lower poles of the remaining kidney. Similar surgery was performed at the same time in sham-operated control rats, but without kidney excision. After 1 week of recovery, and 1 additional week of acclimatization, the animals were randomized (n = 10/group). The rats were housed 2 per cage, at an ambient temperature of 22 ± 2°C, hygrometry of 45% ± 10%, in a room with 12/12 light/dark cycles. The animals had access to water and food ad libitum.

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: The purpose of this preclinical study was to investigate whether moderate chronic kidney disease is a factor in potentiating gadolinium (Gd) uptake in the brain.

Materials and methods: A comparative study was performed on renally impaired (subtotal nephrectomy) rats versus rats with normal renal function. The animals received 4 daily injections of 0.6 mmol Gd/kg a week for 5 weeks (cumulative dose of 12 mmol Gd/kg) of gadodiamide or saline solution. The MR signal enhancement in the deep cerebellar nuclei was monitored by weekly magnetic resonance imaging examinations. One week after the final injection, the total Gd concentration was determined by inductively coupled plasma mass spectrometry in different regions of the brain including the cerebellum, plasma, cerebrospinal fluid, parietal bone, and femur.

Results: After the administration of gadodiamide, the subtotal nephrectomy group presented a significantly higher T1 signal enhancement in the deep cerebellar nuclei and a major increase in the total Gd concentration in all the studied structures, compared with the normal renal function group receiving the same linear Gd-based contrast agent. Those potentiated animals also showed a pronounced hypersignal in the choroid plexus, still persistent 6 days after the last injection, whereas low concentration of Gd was found in the cerebrospinal fluid (<0.05 μmol/L) at this time point. Plasma Gd concentration was then around 1 μmol/L. Interestingly, plasma Gd was predominantly in a dissociated and soluble form (around 90% of total Gd). Total Gd concentrations in the brain, cerebellum, plasma, and bones correlated with creatinine clearance in both the gadodiamide-treated groups.

Conclusions: Renal insufficiency in rats potentiates Gd uptake in the cerebellum, brain, and bones.

No MeSH data available.