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Published on: January 7, 2013
Effects of pre- and postnatal cysteamine exposure on renal function in the rat
F K Assadi1, P McCue, S Jefferis
1Division of Nephrology, Department of Pediatrics, Alfred I. duPont Hospital for Children and Thomas Jefferson University, P.O. Box 269, Wilmington, DE 19899-0269, USA. fassadi@nemours.org
Insights
Cysteamine therapy in pregnant rats did not impact fetal kidney development or offspring renal function. Further studies are needed to confirm safety in human pregnancies involving cystinosis treatment.
Area of Science:
- Nephrology
- Pharmacology
- Developmental Biology
Background:
- Cystinosis treatment with cysteamine improves patient health, increasing pregnancy likelihood.
- Assessing cysteamine safety during pregnancy and post-renal transplantation is crucial for affected individuals.
Purpose of the Study:
- To evaluate the effects of prenatal and early postnatal cysteamine exposure on renal development and function in rats.
- To determine if cysteamine impacts fetal kidney histology and offspring renal function.
Main Methods:
- Pregnant rats received varying oral doses of cysteamine during critical developmental periods (gestation days 6.5-18.5 or 6.5-19.5).
- Fetal kidneys were histologically examined; offspring renal function was assessed at postnatal day 35.
- In a second study, pups also received cysteamine postnatally to mimic maternal exposure levels.
Main Results:
- No significant histological changes were observed in fetal kidneys, even in those with growth retardation or malformations.
- Prenatal and postnatal cysteamine exposure did not lead to alterations in renal function in the offspring at day 35.
- Rat studies indicate cysteamine therapy does not adversely affect renal development.
Conclusions:
- Cysteamine therapy appears safe for renal development in rats during pregnancy and early life.
- These findings suggest a potential for safety in human pregnancies, but further investigation is warranted.
- Human studies are required to definitively establish the safety of cysteamine for renal development during pregnancy.
Abstract:
The safety of cysteamine after renal transplantation and during pregnancy is an important issue, since girls with cystinosis are in better health on cysteamine therapy and thus more likely to become pregnant. In the first study, cysteamine was given to pregnant rats on days 6.5-18.5 post conception in oral doses of 0, 37.5, 75, 100, and 150 mg/kg per day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5-19.5 post conception in oral doses of 0, 37.5, 50, and 75 mg/kg per day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4-21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, there were no alterations in renal function in offspring on day 35. These findings demonstrate that cysteamine therapy does not affect renal development in the rat. Further investigations will be required to prove whether cysteamine therapy has the potential to affect renal development in the human.
