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Functional renal maturation in rat neonates after prenatal exposure to furosemide
1Laboratoire de Néphrologie, Faculté de Médicine de Nancy, Vandoeuvre Les Nancy, France.
Insights
Maternal furosemide exposure in pregnant rats impaired neonatal kidney function, causing urinary concentrating defects and electrolyte imbalances. While some recovery occurred, the renal concentrating defect persisted even after full nephrogenesis.
Area of Science:
- Nephrology
- Developmental Biology
- Pharmacology
Background:
- Prenatal exposure to certain medications can impact fetal development.
- Furosemide is a diuretic that affects kidney function.
- Understanding the long-term effects of prenatal drug exposure on renal maturation is crucial.
Purpose of the Study:
- To investigate the effects of maternal furosemide administration during pregnancy on the functional renal maturation and electrolyte handling in rat neonates.
- To assess kidney function at specific postnatal days (PD1, PD5, PD12).
Main Methods:
- Pregnant rats were administered furosemide (75 mg/kg/day) during critical periods of gestation (organogenesis and nephrogenesis).
- Neonatal rat kidney function, including urinary concentrating ability and electrolyte handling, was evaluated on postnatal days 1, 5, and 12.
Main Results:
- Neonates exposed to maternal furosemide exhibited impaired urinary concentrating ability, hyperdiuresis, and altered electrolyte transport on PD1 and PD5.
- A progressive functional recovery in electrolyte handling was observed from PD1 to PD12.
- Despite the completion of nephrogenesis by PD12, the renal concentrating defect persisted.
Conclusions:
- Maternal furosemide exposure during gestation can lead to persistent defects in renal concentrating ability in offspring.
- The findings suggest a potential drug-induced delay in the development of the loop of Henle.
- This delay may necessitate functional and morphological adaptations in other nephron segments.
Abstract:
We investigated the pattern of functional renal maturation and electrolyte handling on postnatal day 1, (PD1), day 5 (PD5), and day 12 (PD12) in rat neonates, after mothers were given furosemide during pregnancy. The drug was administered (75 mg/kg per day i.p.) on day 7-11 (organogenesis) and 14-18 (nephrogenesis) of gestation. On PD1 and PD5, there was a disturbance of the urinary concentrating ability with a hyperdiuresis and an over-stimulated ionic exchange, mainly the distal sodium reabsorption. From PD1 to PD12, a progressive functional recovery in electrolyte handling appeared. However, on PD12, when nephrogenesis was achieved, the renal concentrating defect remained. We discuss the possibility of a drug-induced delay in the development of the loop of Henle, leading to functional and morphological adaptations of already developed parts of the nephron.