To elucidate the molecular mechanisms underlying renal disease that lead to chronic kidney disease. To validate pathogenic variations in functional in vivo models.
ID
Source
Brief title
Condition
- Renal and urinary tract disorders congenital
- Autoimmune disorders
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Identification of rare known and novel variants (i.e. point mutations and
copy-number variations) underlying chronic kidney disease. These variants are
absent or extremely rare in the normal population.
Secondary outcome
By associating the genetic findings to the clinical data, we additionally aim
to establish genotype-phenotype correlation profiles for all investigated
phenotypes.
Background summary
Chronic kidney disease is a major public health problem resulting in
significant morbidity and mortality. There is ample evidence for familial
aggregation of chronic kidney disease, suggesting a genetic contribution.
However, the genetic architecture of renal diseases is complex, with both
structural variants as well as point mutations contributing to the variability
in phenotypes. Moreover, mutations can have pleiotropic effects (i.e. the same
mutation can lead to different phenotypes) and the inheritance of genetic renal
traits follow a variable mode of inheritance (from X-linked to autosomal
dominant). This complex make-up has hampered gene identification of these renal
diseases until recently. Advancements in genotyping and sequencing methods as
well as bio-informatics now allow discovery of disease-causing rare variants in
(pediatric) renal disease such as congenital anomalies of the kidney and
urinary tract (CAKUT), IgA nephropathy (IgAN), nephrotic syndrome and atypical
hemolytic uremic syndrome (aHUS).
Study objective
To elucidate the molecular mechanisms underlying renal disease that lead to
chronic kidney disease. To validate pathogenic variations in functional in vivo
models.
Study design
Observational genetic studies by using state-of-the art high-throughput genetic
techniques to identify genes implicated in genetic renal disease. In vivo
animal models will be used to validate genetic findings (these studies will be
performed at the coordinating center at Columbia University, New York, USA;
patients will be recruited at the VU University Medical Center, Amsterdam, NL).
Study burden and risks
DNA will be obtained during the single routine, clinically indicated,
venapunction at the outpatient clinic of the department of pediatric nephrology
at the VU University Medical Center. As genetic renal diseases predominantly
present during childhood, these studies will predominantly performed in minors.
Because risks of participating are absent and no extra invasive procedures are
necessary, the burden of participation in this study is negligible. Moreover,
it is reasonable to expect that this study will increase our understanding of
the pathophysiological mechanism of severe renal diseases, which imply major
implications for the development of novel methods for diagnosis and treatment
of subjects.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
Subjects with genetic renal disease (congenital anomalies of the kidney and urinary tract, IgA-nefropathy (biopsy proven), nephrotic syndrome, atypical haemolytic uremic-syndrome (biopsy proven), cystinosis, renal tubulopathies) or children with a high susceptibility for genetic disease due to multiple extra-renal malformations (syndrome) or a positive family history
All ages
Exclusion criteria
Absence of informed consent
Pathogenic variant already known before study inclusion
Disapproval to be informed on genetic findings that are associated with hereditary diseases in later life (e.g. breast cancer, colon cancer, Huntington's disease)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL43517.029.14 |