Development of a predictive test for r-FSGS at the individual level of a patient and kidney donor with FSGS.
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main outcome is the proportion of assay results that correctly reflect clinical
outcome of r-FSGS (podocyte damage in r-FSGS; no podocyte damage in non r-FSGS).
Main outcome will be based on podocyte damage according to chosen assays to
demonstate podocyte damage caused by FSGS patient plasma. Results will be
linked to the clinical data of the patients in the pre-specified groups of
r-FSGS and non r-FSGS. Podocyte damage caused by FSGS patient plasma will be
assessed in comparison with control plasma (from kidney donors).
Secondary outcome
Secondary outcome measures:
1. the response of induced patient podocytes to blood plasma of the same
patient (positive control);
2. the response of induced patient and donor podocytes to blood plasma of the
kidney donor (negative controls);
3. if the primary outcome is favorable, the response of other donor and patient
podocytes to FSGS patient plasma will be evaluated.
Background summary
Focal segmental glomerulosclerosis (FSGS) is a kidney disease that manifests
with heavy protein leakage to the urine. The main histological feature is
damage to podocytes, which are specialized epithelial cells of the kidney
filtering organs (glomeruli). FSGS often leads to loss of kidney function, and
recurs within days after transplantation in approximately 50% of patients.
Clinical and experimental observations suggest that a circulating factor
causing podocyte damage is involved in the pathogenesis of post-transplant FSGS
recurrence (r-FSGS). However, the responsible factor has remained unidentified
despite intense research. A highly predictive test/model for r-FSGS is urgently
needed. The central hypothesis of this project is that the event of r-FSGS
depends on interactions between patient plasma and donor podocytes. The project
aims to develop an individualized test for r-FSGS. The proposed test model is
based on evaluation of damage to induced kidney donor podocytes (derived from
blood cells) by patient blood plasma. To demonstrate a proof of concept, we
will include patient and donor pairs with known outcome after transplantation.
Study objective
Development of a predictive test for r-FSGS at the individual level of a
patient and kidney donor with FSGS.
Study design
Experimental pilot study for development of a predictive assay for r-FSGS.
Study burden and risks
Burden and risks associated with participation are minimal. A single visit to
the outpatient clinic is required to perform one single venipuncture. We will
draw 40 mL of heparanized blood for peripheral blood mononuclear cells (PBMCs)
reprogramming into iPSCs and plasma storage. 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 predict r-FSGS with a
specific donor, or even avoidance of this risk by selection of a suited donor.
The risk benefit ratio is therefore very acceptable.
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
Population:
1. Adult patients (18 years or older) with diagnosis of FSGS in the native kidneys, and known outcome after kidney transplantation (recurrent FSGS or non-recurrent FSGS).
2. Living persons who have previously donated a kidney to patients specified under 1.;Inclusion criteria
1. Established outcome after kidney transplantation (recurrence or non-recurrence of FSGS);
2. Living kidney donation;
3. Donor available for participation in the study
Exclusion criteria
1. Follow-up after transplantation too short to rule out development of late FSGS recurrence (less than one year);
2. Unknown histological diagnosis in the native kidney;
3. No communication between patient and donor.
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 | NL69759.091.19 |