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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.


Individual CrCl values (mean of the 2 determinations) of the 4 different groups.
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Figure 2: Individual CrCl values (mean of the 2 determinations) of the 4 different groups.

Mentions: Figure 2 shows the mean of the CrCl values (determined before and after the injection period). A slight but statistically significant recovery in CrCl was observed in both SNx groups between the beginning and end of the study (respectively, saline + SNx: 0.19 ± 0.02 mL/min/100 g vs 0.24 ± 0.05 mL/min/100 g, P = 0.02; gadodiamide + SNx: 0.20 ± 0.08 mL/min/100 g vs 0.26 ± 0.09 mL/min/100 g, P = 0.002), whereas the CrCl of animals with normal renal function remained stable (saline sham: 0.49 ± 0.13 mL/min/100 g vs 0.51 ± 0.07 mL/min/100 g, P = 0.71 not significant [NS]; gadodiamide sham: 0.51 ± 0.18 mL/min/100 g vs 0.51 ± 0.20 mL/min/100 g, P = 0.85 [NS]). Subtotal nephrectomy resulted in a decrease in renal function by 63% ± 11% compared with the animals with normal renal function at the start of the study, the gap reduced to 53% ± 13% at the end of the study (week 6). Gadodiamide did not significantly impact CrCl compared with saline, in both the sham-operated (P = 0.35) and SNx groups (P = 0.47).


Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats
Individual CrCl values (mean of the 2 determinations) of the 4 different groups.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Individual CrCl values (mean of the 2 determinations) of the 4 different groups.
Mentions: Figure 2 shows the mean of the CrCl values (determined before and after the injection period). A slight but statistically significant recovery in CrCl was observed in both SNx groups between the beginning and end of the study (respectively, saline + SNx: 0.19 ± 0.02 mL/min/100 g vs 0.24 ± 0.05 mL/min/100 g, P = 0.02; gadodiamide + SNx: 0.20 ± 0.08 mL/min/100 g vs 0.26 ± 0.09 mL/min/100 g, P = 0.002), whereas the CrCl of animals with normal renal function remained stable (saline sham: 0.49 ± 0.13 mL/min/100 g vs 0.51 ± 0.07 mL/min/100 g, P = 0.71 not significant [NS]; gadodiamide sham: 0.51 ± 0.18 mL/min/100 g vs 0.51 ± 0.20 mL/min/100 g, P = 0.85 [NS]). Subtotal nephrectomy resulted in a decrease in renal function by 63% ± 11% compared with the animals with normal renal function at the start of the study, the gap reduced to 53% ± 13% at the end of the study (week 6). Gadodiamide did not significantly impact CrCl compared with saline, in both the sham-operated (P = 0.35) and SNx groups (P = 0.47).

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.