Loss of a kidney during fetal life: long-term consequences and lessons learned

Area of Science:

• Pediatric Nephrology
• Developmental Biology
• Renal Physiology

Background:

• Children with a solitary functioning kidney (SFK) are prone to renal insufficiency and hypertension.
• Congenital SFK arises from conditions like unilateral renal agenesis or multicystic kidney dysplasia.
• The single kidney undergoes structural and functional adaptations to compensate for reduced nephron mass.

Purpose of the Study:

• To investigate the mechanisms of early renal insufficiency development in fetal SFK.
• To understand the long-term functional consequences of congenital solitary kidney.
• To identify potential sex differences in renal adaptation to kidney loss.

Main Methods:

• Established a fetal uninephrectomy (uni-x) sheep model, mimicking congenital SFK.
• Sheep complete nephrogenesis before birth, similar to humans.
• Monitored arterial pressure, renal function, and compensatory nephrogenesis over time.

Main Results:

• The uni-x sheep model showed a 30% reduction in nephron number due to compensatory nephrogenesis.
• Uni-x sheep exhibited progressive increases in arterial pressure and declining renal function with age.
• Significant sex differences were observed in the functional adaptations of the remaining kidney.

Conclusions:

• Fetal kidney loss leads to compensatory changes that ultimately impair renal function and increase blood pressure with age.
• The sheep model provides insights into the pathophysiology of renal insufficiency in individuals with SFK.
• Understanding these adaptations is crucial for managing long-term health outcomes in children with SFK.