| Registry | NCT06334692, acronym BLINDER |
|---|---|
| Status | Recruiting |
| Study type | Observational |
| Enrollment | 100 (Estimated) |
| Sponsor | Mario Negri Institute for Pharmacological Research (Other) |
| Conditions | Nephrotic Syndrome |
| Interventions | In-house ELISA, and ELISA kits from "DBA Italy" (Abbexa). (Diagnostic test) |
| Dates | start 2024-03-19, primary completion 2028-03-01 (estimated), completion 2028-03-01 (estimated), first posted 2024-03-28, last updated 2025-09-04 |
| Locations | 1 site in Italy |
Related Papers Related Patents Related Grants Related Experts
All trials for Nephrotic Syndrome All trials of In-house ELISA, and ELISA kits from "DBA Italy" (Abbexa).
This retrospective study is aimed at evaluating the levels of circulating anti-nephrin autoantibodies in patients with INS, including those with MCD/FSGS and in patients who have experienced relapse of FSGS post-transplant, compared to those of a control group of patients with nephrotic syndrome due to primary membranous nephropathy (MN).
Nephrotic syndrome (NS) is one of the major "unsolved problems" in nephrology and represents a long-standing challenge in terms of pathogenetic mechanisms and the search for an effective cure.
Nephrotic-range proteinuria (>3.5 g/day) is accompanied by a set of abnormalities collectively known as NS. It is characterized by systemic complications resulting from alterations in the composition of the body's protein pool, sodium retention, dyslipidemia, coagulation factor abnormalities and a variable degree of renal failure. When secondary causes cannot be identified, the clinical presentation is called idiopathic nephrotic syndrome (INS). INS is associated with disappearance of podocyte pedicels (visible under the electron microscope) and minimal changes (minimal change disease, MCD) or, at the more advanced stage, focal segmental glomerulosclerosis (FSGS) under the light microscope. INS can be treated with corticosteroids, which represent the first-line treatment, however, among the forms of NS, FSGS has the lowest rate of response to therapy. More importantly, in 30% of patients with FSGS, disease recurrence develops rapidly after transplantation, sometimes within minutes or hours, and leads to the immediate onset of proteinuria and graft dysfunction. For post-transplant FSGS recurrence, no prevention or treatment strategies are available and current therapeutic approaches are mostly based on clinical experience.
The recurrence of FSGS in the transplanted kidney presupposes the presence of one or more circulating factors of extrarenal origin which can selectively affect and damage the glomerular barrier, in particular the podocytes, resulting in massive proteinuria. However, the identity, nature and cellular source of factors circulating in the INS are not yet known.
Recent evidence of the therapeutic efficacy of anti-B cell antibodies in inducing and/or maintaining remission in patients with INS indicates the presence of possible B cell dysfunction.
In support of this, a recent study described the presence of anti-nephrin autoantibodies (a structural component of the podocyte slit diaphragm) in a subgroup of pediatric and adult patients with MCD. These autoantibodies were present during the active phase of the disease, and were associated with a punctate staining of IgG in renal biopsies in correspondence with the specific areas of presence of nephrin. Furthermore, the presence of autoantibodies against nephrin has been found in early post-transplant FSGS recurrence. This preliminary result was confirmed by a Japanese multicenter study conducted on 11 pediatric patients with post-transplant FSGS recurrence. In these patients, anti-nephrin autoantibodies were elevated both before transplantation and during disease relapse and were related to punctate deposition of immunoglobulins G (IgG) that colocalized with nephrin in the graft biopsy at the time of relapse. This recent evidence suggests that circulating anti-nephrin antibodies represent a possible circulating factor involved in the pathogenesis of INS, in particular post-transplant FSGS recurrence.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Cases | Diagnostic Test: In-house ELISA, and ELISA kits from "DBA Italy" (Abbexa). | Sera from patients with biopsy-proven idiopathic MCD or FSGS who provided consent to store their samples in the certified biobank (Mario Negri Biological Resources Centre - Rare Diseases and Renal Diseases Biobank - CRB). Serum samples will be tested for the levels of anti-nephrin autoantibodies by in-house ELISA and results confirmed by commercial ELISA kits. | |
| Controls | Diagnostic Test: In-house ELISA, and ELISA kits from "DBA Italy" (Abbexa). | Sera from patients with biopsy-proven idiopathic membranous nephropathy who provided consent to store their samples in the certified biobank (Mario Negri Biological Resources Centre - Rare Diseases and Renal Diseases Biobank - CRB). Samples will be tested for the levels of anti-nephrin autoantibodies by in-house ELISA and results confirmed by commercial ELISA kits. |
Sex: All, ages: 18 Years to any
Inclusion Criteria: * Adult (>18 years) males and females * Patients with biopsy-proven idiopathic MCD or FSGS (cases) * Patients with biopsy-proven idiopathic membranous nephropathy (controls) * Patients who provided consent to store their samples in the certified CRB biobank Exclusion Criteria: * Reasonable possibility of a secondary cause of NS (for cases) or MN (for controls) at time of blood collections * Active viral or bacterial infections at time of blood collections
| Facility | City | Country | Status |
|---|---|---|---|
| Clinical Research Center for Rare Disease Aldo e Cele Daccò | Ranica, BG | Italy | Recruiting |