1. To evaluate if podocytes directly cultured from the urine, and podocytes derived from induced pluripotent stem cells (iPSCs), can be used to prove causality of the VUS.2. Comparison of results obtained using iPSC-derived and urinary podocytes,…
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Abnormal function of podocytes from patients with proven disease causing
mutations compared to disease and healthy controls.
Secondary outcome
Not applicable
Background summary
Kidney diseases can be caused by mutations in genes that encode proteins
involved in the functioning of epithelial cells of kidney filtering organs
(podocytes) or the composition of the basement membranes. With increased use of
DNA-sequencing, and the discovery of disease-causing mutations in the
non-coding DNA (INTRONS), we now see many patients with a *genetic variant of
unknown significance (VUS)*.
Study objective
1. To evaluate if podocytes directly cultured from the urine, and podocytes
derived from induced pluripotent stem cells (iPSCs), can be used to prove
causality of the VUS.
2. Comparison of results obtained using iPSC-derived and urinary podocytes,
respectively.
Study design
1. Reprogramming of peripheral blood mononuclear cells (PBMC) obtained from
patients and controls into induced pluripotent stem cells at the Radboudumc
Stem Cell Technology Center (SCTC);
2. Induction of podocyte development from iPSCs, and culturing of podocytes
from urinary cells at the Department of Pathology Research laboratory;
3. Evaluation of podocyte function (mRNA production, motility, protein
expression patterns).
Study burden and risks
Burden and risks associated with participation are minimal. A single visit to
the outpatient clinic is required to obtain informed consent (IC) and perform
one single venipuncture. We will draw 40 mL of heparanized blood for peripheral
blood mononuclear cells (PBMC) reprogramming into iPSCs. We will also obtain a
freshly voided urine for the purpose of podocyte culturing. No additional tests
are required. Although the project is highly experimental, the benefit for
patients will be potential development of a test that can be used to confirm
disease-causality of a documented genetic variant. The risk benefit ratio is
therefore very low.
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
1. Patients
* Established diagnosis of collagen IV nephropathy with disease-causing Col4
mutation.
2. Disease controls:
* diagnosis of focal segmental glomerulosclerosis (FSGS) with no evidence of
underlying genetic mutations.
3. Healthy controls:
* no signs of kidney disease, negative family history of kidney diseases (i.e.
proteinuria or hematuria with no proven cause).
Exclusion criteria
* Unspecified kidney injury;
* Not able to provide informed consent.
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 | NL69788.091.19 |