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Induction of an experimental Fanconi syndrome in mice: its effect on the glomerular filtration function studied by
C Sawas-Dimopoulou1, I Sigalas, L Margaritis
1Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research Demokritos, AG. Paraskevi Attiki, Greece.
Abstract:
An experimental mice model of maleate (MAL)-induced Fanconi syndrome has been used to test 99mTc-DTPA ability to detect hampered glomerular filtration rate (GFR) early in drug-induced Fanconi syndrome. In fact, declining GFR has been reported both in idiopathic and acquired Fanconi syndrome. The above MAL model shows urine biochemistry changes similar to those reported in patients suffering from Fanconi syndrome. Moreover, biodistribution study and whole-body autoradiographies performed after IV injection of 99mTc-DTPA in MAL and control mice show significantly delayed pharmacokinetics of the above radiopharmaceutical in a MAL dose-dependent effect. After administration of a MAL dose of 6 mM/kg BW, the 5-min biodistribution of 99mTc-DTPA, a radiopharmaceutical freely excreted by glomerular filtration, is significantly changed in all organs. In blood of MAL mice, 27.62 +/- 2.86% of the injected dose is still circulating compared to 13.67 +/- 1.22% of the injected dose in control mice, and only 1.37 +/- 0.31% of the injected dose has been excreted in urine of MAL mice compared to 24.66 +/- 4.12% of the injected dose in urine of control mice. The obtained results suggest that 99mTc-DTPA may be efficient both in the early detection of abnormal GFR in acquired Fanconi syndrome after application of a nephrotoxic treatment, and in the follow-up of patients in recovery phase after discontinuation of the therapy.
Insights
99mTc-DTPA effectively detects reduced glomerular filtration rate (GFR) in a maleate-induced Fanconi syndrome mouse model. This radiopharmaceutical shows promise for early diagnosis and patient monitoring in acquired Fanconi syndrome.
Area of Science:
- Nephrology
- Radiopharmacology
- Experimental Medicine
Background:
- Fanconi syndrome, characterized by declining glomerular filtration rate (GFR), can be idiopathic or acquired.
- Maleate (MAL) induces experimental Fanconi syndrome in mice, exhibiting urine biochemistry changes similar to human patients.
- Early detection of compromised GFR is crucial for managing drug-induced kidney injury.
Purpose of the Study:
- To evaluate the diagnostic potential of 99mTc-DTPA for early detection of impaired GFR in a maleate-induced Fanconi syndrome mouse model.
- To assess the pharmacokinetics of 99mTc-DTPA in mice with experimentally induced Fanconi syndrome.
- To determine if 99mTc-DTPA can aid in monitoring kidney function recovery.
Main Methods:
- Induction of Fanconi syndrome in mice using maleate (MAL).
- Intravenous injection of 99mTc-DTPA, a glomerularly filtered radiopharmaceutical.
- Biodistribution studies and whole-body autoradiography to analyze 99mTc-DTPA pharmacokinetics.
- Comparison of 99mTc-DTPA distribution and excretion in MAL-treated mice versus control mice.
Main Results:
- Maleate-induced Fanconi syndrome mice exhibited significantly delayed 99mTc-DTPA pharmacokinetics in a dose-dependent manner.
- In MAL mice, a higher percentage of injected 99mTc-DTPA remained in circulation at 5 minutes post-injection compared to controls.
- Urine excretion of 99mTc-DTPA was significantly reduced in MAL mice, indicating hampered glomerular filtration.
Conclusions:
- 99mTc-DTPA demonstrates efficacy in the early detection of abnormal GFR in acquired Fanconi syndrome.
- The radiopharmaceutical can potentially be used to monitor kidney function during recovery after cessation of nephrotoxic therapy.
- This study supports the utility of 99mTc-DTPA as a diagnostic tool for drug-induced kidney injury affecting GFR.