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A groundbreaking discovery by researchers at the Hadassah Medical Organization (HMO) could eventually help doctors protect premature babies from kidney disease throughout their lives.
Working with scientists at Monash University in Australia, HMO researchers identified a cellular mechanism that may help explain why premature birth is associated with lifelong kidney vulnerability — and a potential window for future treatments.
Published in iScience, a Cell Press journal, the study offers new insight into how the earliest days of life can shape kidney health for decades.
Approximately one in 10 babies worldwide is born prematurely. Previous research has linked premature birth to an increased risk of chronic kidney disease, but the biological mechanism behind that risk has remained unclear.
When Developing Cells Switch Into Survival Mode
Using a mouse model of premature birth, researchers discovered that the sudden transition from the womb to the outside world triggers a stress response in developing kidney cells.
Instead of continuing to produce nephrons, the tiny filtration units that remove waste from the blood, the cells temporarily shift their focus to survival. When they begin developing again, they can't make up for the lost time, leaving the kidneys with fewer filtration units.
Because nephrons develop before or around birth and cannot naturally regenerate once development ends, this shortage can leave the kidneys more vulnerable to damage throughout life.
"We have known for years that children born prematurely reach adulthood with more vulnerable kidneys, but we didn't know exactly what went wrong and when," said Dr. Morris Nechama of HMO's Pediatric Nephrology Unit, who led the study. "Here we saw it happen in real time: nephron progenitor cells enter distress within the first hours after birth, and their timing is disrupted. They try to compensate later, but the window has already closed."
In one surprising finding, the period during which new nephrons could develop lasted approximately 24 hours longer in premature mice. Yet even this additional time was not enough to overcome the disruption.
The researchers also found signs of kidney damage as the animals matured, suggesting that developmental changes beginning shortly after birth can have lasting consequences.
A Potential Window for Treatment
By identifying the cellular stress response associated with disrupted kidney development, researchers have uncovered a possible opportunity for intervention during the first days after premature birth, what they described as a "critical therapeutic window."
Research Without Borders
The study was led by Dr. Nechama and Athar Amleh, a doctoral student conducting her research at HMO and the study's first author, and co-authored by Dr. Oded Volovelsky, director of HMO's Pediatric Nephrology Unit, and Prof. Alexander Combes of the Monash Biomedicine Discovery Institute.
Supported in part by AUSiMED, an Australian organization that promotes collaborative medical research, the teams continued their work throughout the war, with experiments conducted in Jerusalem and data analysis taking place in Melbourne.
"We accompany children born prematurely in the clinic and see the result years later, sometimes only in adolescence," said Dr. Volovelsky. "This study indicates that the first few days after birth are not only a period of survival but also a period in which the kidney's reserve for life is set."
