Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06334692
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-11
First Post:
2024-03-15
Brief Title:
Autoantibodies Against-nephrin in Idiopathic Nephrotic Syndrome
Sponsor:
Mario Negri Institute for Pharmacological Research
Organization:
Mario Negri Institute for Pharmacological Research
Study Overview
Official Title:
Autoantibodies Against-nephrin in Idiopathic Nephrotic Syndrome
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BLINDER
Brief Summary:
This retrospective study is aimed at evaluating the levels of circulating anti-nephrin autoantibodies in patients with INS including those with MCDFSGS 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
Detailed Description:
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 35 gday 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 bodys 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 andor 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
Nephrotic-range proteinuria 35 gday 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 bodys 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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None