Child research

CONGENITAL AND HEREDITARY DISORDERS
truly connected
interdisciplinary
Our
network
enables swift transition
from bedside to bench
and back, directly
supporting improvement
of care for vulnerable
patients.
- Marc Lilien
Kidney
and Urinary tract
An end stage renal disease patient is
referred to the outpatient clinic for
hereditary renal disease: The patient is
diagnosed with an autosomal dominant
renal disease. Recently, his first child was
born with an autosomal dominant renal
disease. This does not recur in a kidney
graft. His eldest (at 50% risk) was
subsequently evaluated at the pediatric
hereditary renal disease outpatient clinic.
Wishing to further establish their family,
the couple was informed about their
options and chose to try to conceive using
preimplantation genetic diagnosis.
aeerde@umcutrecht.nl
mlilien@umcutrecht.nl
Albertien van Eerde
MD, PhD is clinical
geneticist at the UMC
Utrecht who specializes
in nephrogenetics. She’s
the coordinator of the
Expert Center for
Hereditary and Congenital
Renal and Urinary
Tract Disorders, which is
accredited both
nationally and by the EU
(through ERKNET).
Marc Lilien MD,
PhD is a pediatric
nephrologist at the
Wilhelmina Children’s
Hospital and has
expertise in renal
ciliopathies and renal
tuberous sclerosis
phenotypes.
Our research in the kidney and urinary tract
focuses on clinical expertise in the nationally
accredited Center of Expertise for Hereditary and
Congenital Nephrologic and Urologic Disorders.
The Expert Center ensures optimal care and
research for families with renal disease and spans
infancy to adulthood, including preconception
and prenatal care. It encompasses (pediatric)
nephrology, (pediatric) urology, clinical and
laboratory genetics, obstetrics, nephropathology,
radiology, and we participate in ERKnet:
the European Reference Network for Rare
Kidney Disease.
The case above is a good clinical example of the
interdisciplinary nature of our work. When a
diagnosis is challenging or undetermined, we
incorporate genetic testing and functional follow
up. This has proven effective for the ITGA3 gene.
For insights into cystinosis-related phenotypes,
we collaborate with Roos Masereeuw, PhD at
Utrecht University who is an expert on how
pharmacologics affect molecular pathways, and
to further investigations into new candidate
genes we collaborate with the Antignac’s group
in Paris.
We also perform cohort-based research. Albertien
has shown that NPHP1 gene deletions can cause
adult renal disease, which comprises about 0.5%
of adult end stage renal disease at all ages. This
challenges the paradigm that nephronophthisis is
primarily a pediatric renal disease, and has
consequences for follow up into adulthood and
kidney donation, especially by siblings. We both
actively participate in the AGORA cohort (for
example, patients with congenital anomalies of
the kidney and urinary tract and renal ciliopathies).
Marc has recently published a detailed overview
of renal ciliopathy phenotypes, and steps towards
early biomarkers.
With a recently acquired Dutch Kidney Foundation
grant, Albertien will further establish a registry of
patients with rare renal diseases, and will build a
Kidney Gene Regulatory Network. We both also
want to further the understanding of “renal
sensitivity”: What drives the variability in severity
in patients with similar genetic predisposition or
toxic exposure.
Genetic diagnoses have an effect in the full circle
of life. And they are too often missed, especially in
adult nephrology. Together, our research activities
create synergy and we’re able to create impact for
instance, by developing informational material
(like online movies) for patients, by conceiving a
national guideline for genetic testing in (pediatric)
nephrology and by teaching pediatricians,
nephrologists and geneticists, nationally and
internationally. We often work together with the
Dutch Kidney Patient Association.
UMC Utrecht - Child research 17