ERKNet

The European Rare Kidney Disease Reference Network

  

Research Project

Project Title:

Study of the pathogenetic mechanisms underlying post-transplant disease recurrence in patients with idiopathic focal segmental glomerulosclerosis (PARSEC study)

Project Type:

Translational research

Disease group(s):

Hereditary glomerulopathies, Immune glomerulopathies

Project Summary:

Aims of the study
1) To evaluate the pattern of abnormalities in the innate and/or adaptive immune system patients with post-transplant FSGS recurrence.
2) To establish whether any of the abnormalities identified in aim 1 predicts post transplant FSGS recurrence.

The study is divided in two phases: 1) Case-control study; 2) Cohort Prospective Study.

Primary outcomes - Case-control study
Differences between case and control groups in:
- Absolute values of cytokine levels (IL-13, TNFα, IL-4, IL-10 and CLC-1) and IgE, IgG4, sCD23 in serum and supernatant of resting PBMC.
- Phenotype of B-cells / T-cells and the percentages of these cells expressing activation markers in PBMC before and after stimulation in vitro.
- Absolute values of serum BAFF.
- Presence, number and localization of infiltrating T and B cells, neutrophils and monocytes, along with IgE and IgG4 deposition in kidney biopsies.
- Absolute values of complement levels (C3, C4, C5a and sC5b-9) in serum and in the supernatant of cultured resting and activated PBMC
- C3 / C5b-9 and DAF staining on the surface of cultured resting and activated PBMC.
- Presence and distribution of C3 and C5b-9 deposits along with DAF staining/expression in kidney biopsies.

Primary outcomes - Cohort Prospective Study
- Differences between cases and controls in the two cohorts analyzed separately or together in pre-transplant values of parameter(s) that will be found selectively altered in cases of aim 1.
- Power of the selected parameter(s) to predict post-transplant FSGS recurrence.

Inclusion criteria - Case-control study
- Case group: patients > 18 years old who have had a biopsy-proven FSGS recurrence in the kidney graft after renal transplantation, which led to end-stage renal disease with subsequent need for hemodialysis.
- Control group 1: patients > 18 years with genetic FSGS (with identified mutations in podocytes genes) and end-stage renal disease on hemodialysis.
- Control group 2: patients > 18 years with polycystic kidney disease and end-stage renal disease
on hemodialysis.
- Control group 3. Healthy subjects > 18 years.

Inclusion criteria - Cohort Prospective Study
- Cohort 1 (idiopathic FSGS) : patients > 18 years with end-stage renal disease and a biopsy-proven FSGS diagnosis, with a negative sequencing analysis for pathogenic mutations in genes associated with FSGS (see methods for the full list), who are undergoing renal transplantation.
- Cohort 2 (genetic FSGS) : patients > 18 years with end-stage renal disease and a biopsy-proven FSGS diagnosis, with a positive sequencing analysis for pathogenic mutations in genes associated with FSGS, who are undergoing renal transplantation.

Exclusion criteria
Patients <18 years old.

Lead principal investigator(s):

Giuseppe Remuzzi, Bergamo

Co-investigator(s):

Perico Norberto, Bergamo

Project Period:

05/2017   -   05/2020

Sponsors:

Non-profit foundation

Project web page:

http://registro.marionegri.it/frontend_eng/interno.php?id_studio=273

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