- Study identifies possible therapeutic target to increase nephron numbers in the developing kidney of preterm infants.
- Statistics estimate about one in 10
infants (approximately 387000 births) are born preterm before 37 week in
the U.S each year. Of these, nearly 109,000 are considered "early"
preterm births (before 34 weeks).
- Preterm infants are at increased
risk of developing kidney failure later in life due to interrupted kidney
development, needing dialysis and renal transplant.
Targeting the protein
hamartin could extend kidney development in preterm babies and reduce the risk
of kidney failure later in life according to a recent study by scientists at Cincinnati
Children's. The team are currently trying to understand the driving factors (genetic
and environmental) behind preterm birth and see if it would be possible to
reduce the incidence of preterm deliveries.
The findings of the
study appear in the journal PNAS.
Aim of Study
The team hope to find what factors determine the number of
nephrons we have as adults and how this number could be increased
‘Targeting the protein hamartin has the potential to regulate the number of nephrons in the kidney and reduce risk of kidney failure in preterm infants.’
the nephrons you or I have were generated while we were in our mother's uterus.
Prematurity terminates this process too early. As a result, adults that were
born prematurely are at high risk for hypertension, heart disease and end stage
renal disease," says Raphael Kopan, PhD, Director of the Division of
Developmental Biology at Cincinnati Children's, and senior author of today's
question we tried to address is how we generate the specific number of nephrons
we have as adults, and how can we increase this number in premature
Discovering Possible Factors That Regulate Nephron Formation
- Details of Study
The team studied mice
to determine how nephron
numbers in the kidney are regulated.
- The scientists discovered that a
protein called hamartin plays a key
role in shutting down the nephron formation process.
now, this protein was primarily known as a factor associated with tuberous sclerosis
complex, a rare genetic
condition that causes benign tumors to grow in the kidneys, brain, heart, and
- In the current study, when mice were
programmed to produce decreased
amounts of hamartin, their kidneys developed 25 percent more number of nephrons than a control
- However, when the mice were programmed to produce no
hamartin at all, the mice developed lethal kidney defects.
Thus, the findings of the
study appear to suggest that reducing
the amount of hamartin either during pregnancy or after delivery could promote
development. These findings were seen in mice with two different
genetic backgrounds, suggesting that hamartin function was not influenced by
the method the research team used to reduce its level.
study provides important new information that will improve outcomes for all
babies born prematurely," says Louis Muglia, MD, PhD, Co-Director of the
Perinatal Institute at Cincinnati Children's and Director of the Center for
Prevention of Preterm Birth. "Optimizing pregnancy outcomes is a central
focus shared by the basic scientists and clinicians in the Perinatal Institute,
and this work reflects that shared commitment."
Nephrons - The
Functional Units of The Kidneys
are the microscopic functional units of the kidneys that convert toxic and
waste products in the blood into urine, regulate our blood pressure and
maintain electrolyte balance.
kidney contains 1 million nephrons, all of which develop in-utero between weeks
25 to 36 of gestation. Unfortunately, the
nephron formation is interrupted when babies are born preterm,
consequently puts them at higher risk of developing kidney disease
"We never make
another nephron after we are 36 weeks old,"
Kopan says. "It
would be necessary to target at-risk premature babies to try to prolong their
Scope of Study
Although the findings of the study suggest that reducing
hamartin levels would increase kidney development, there is a flip side.
Reducing hamartin levels in people increases the risk of developing tuberous
- The team plans to develop a safe drug to potentially
target hamartin levels that could be delivered shortly after birth of the
- In related research around the
world, scientists are working to
see if MRI scans can be used measure nephron numbers in the kidneys.
Currently studies are focused on adults, but if proven safe, they could
become applicable in newborns.
this would take considerable time and research before the results are deemed
safe and effective to use on patients.
Research At Cincinnati Children's
Children's is a leading collaborator in Cradle Cincinnati, a community-wide
partnership that aims to reduce high preterm birth rates and infant mortality
in Hamilton County.
- Measures such as smoking cessation, having at least a year's gap
between successive pregnancies and safe sleeping habits have helped in
reducing preterm births and infant deaths.
- In a large genetic study, scientists
have identified six genomic locations that could possibly affect birth
remains to be seen how these discoveries will help reduce preterm births.
However, Cradle Cincinnati's programs and the current study are examples how
research and innovation can help identify ways to reduce some of the
complications associated with premature birth and improve the quality of life
for these children as well as their families.
- Helping Preterm Infants Grow Bigger Kidneys Would Prevent Kidney Disease Later in Life - (https://www.cincinnatichildrens.org/news/release/2018/preterm-infants-kidneys)