Ignite Creation Date:
2024-05-06 @ 10:37 AM
Last Modification Date:
2024-10-26 @ 12:32 PM
Study NCT ID:
NCT03305211
Status:
UNKNOWN
Last Update Posted:
2017-10-09
First Post:
2017-10-04
Brief Title:
Biological Collection in Nephrology for the Study of the Links Between Kidney Disease Immunity System and Cardiovascular Complications
Sponsor:
Assistance Publique Hopitaux De Marseille
Organization:
Assistance Publique Hopitaux De Marseille
Study Overview
Official Title:
Biological Collection in Nephrology for the Study of the Links Between Kidney Disease Immunity System and Cardiovascular Complications
Status:
UNKNOWN
Status Verified Date:
2017-10
Last Known Status:
NOT_YET_RECRUITING
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:
NéphroMIC²
Brief Summary:
The NephoMIC project is a biological collection in patients of Nephrology allowing the study of the links between kidney diseases Immunity system and Cardiovascular complications
Its aim is to allow the development of a translational research on the theme of Systemic Nephrology which concerns both renal complications of autoimmune and inflammatory diseases and systemic complications of patients with kidney disease linked to both a state of immunosuppression and an increased risk of cardiovascular complications
It is based on the proximity between the Clinical investigation Center CIC of the hospital where the samples are received techniqued and preserved and the Center of Nephrology and Renal Transplantation of the hospital
The collection includes blood samples whole blood serum plasma total blood RNA PBMC cells and urine samples fresh urine
Participation in the collection is particularly recommended for patients who require a medical renal biopsy in the Nephrology Department Other well-phenotyped patients well-defined renal disease diagnosis may also participate in NephroMIC
Its aim is to allow the development of a translational research on the theme of Systemic Nephrology which concerns both renal complications of autoimmune and inflammatory diseases and systemic complications of patients with kidney disease linked to both a state of immunosuppression and an increased risk of cardiovascular complications
It is based on the proximity between the Clinical investigation Center CIC of the hospital where the samples are received techniqued and preserved and the Center of Nephrology and Renal Transplantation of the hospital
The collection includes blood samples whole blood serum plasma total blood RNA PBMC cells and urine samples fresh urine
Participation in the collection is particularly recommended for patients who require a medical renal biopsy in the Nephrology Department Other well-phenotyped patients well-defined renal disease diagnosis may also participate in NephroMIC
Detailed Description:
Kidney damage to systemic lupus erythematosus SLE anti-cytoplasmic neutrophil cytoplasmic ANCA vasculitis or systemic amyloidosis expose patients to
a risk of renal insufficiency which depends on the severity of the attack the delay in the initiation of treatment and the possible occurrence of relapses which may leave fibrous sequelae and lead to the development of insufficiency chronic renal disease CKD
a risk of immunosuppression and infectious complications linked to the renal insufficiency itself or to the toxicity of immunosuppressive treatments aimed at controlling renal disease
an increased risk of cardiovascular complications linked on the one hand to the activity of the systemic disease and to the endothelial dysfunction it may entail and on the other hand to the cardiovascular risk associated with the IRC
Systemic lupus erythematosus SLE is a chronic autoimmune disease evolving in relapses interrupted by periods of remission Renal impairment of SLE is common 20-30 of patients in Europe 1 and severe 2 with an impact on patient survival 3 and a risk of progression to chronic renal insufficiency IRC Thus nearly 40 of patients with severe form develop IRC 4 and 5-10 have terminal IRC at 10 years 56 The classification of renal involvement according to the International Society of Nephrology Renal Pathology Society ISN RPS 7 distinguishes active proliferative forms requiring immunosuppressive therapy 8 nonproliferative or purely chronic forms However renal biopsy remains an invasive procedure 9 which can hardly be repeatedly performed let alone pre-emptively although the onset of tissue damage precedes the emergence of clinically detectable proteinuria 10 In addition the response of proliferative lupus nephropathy to immunosuppressive therapy is difficult to predict The progression in treatment is favorable in 70 to 80 of patients with proliferative form but 20-30 are refractory to the standard treatment while others retain important chronic lesions leading to chronic renal insufficiency
There is therefore a crucial need for non-invasive biomarkers to identify lupus patients at risk for developing renal disease and to predict the severity of histological involvement and response to immunosuppressive therapy
The investigators believe that the pathophysiological complexity of lupus nephropathy can not be summarized to a single biomarker and that a global omic approach could capture this complexity or identify new pathways
The blood transcriptome study is a non-invasive and usable approach in clinical research which allowed 10 years ago to identify the signature of lupus interferon IFN 11 which had not been detected in serum of patients and led to new therapeutic pathways The complexity and size of pan-genomic transcriptomic data may be an obstacle to their analysis and interpretation 12 Using a modular approach to reduce the size of transcriptomic blood glucose data and facilitate their interpretation the investigators were able to show the gradation of the interferon signature during lupus 13 and describe the link between neutrophil modular signature and renal impairment of lupus 14
In addition the search for noninvasive urinary biomarkers to avoid or limit biopsy indications in the NL or to predict the response to IS treatment to early adapt the intensity is of great interest The current PeptiduLUP study is being conducted to determine the diagnostic and prognostic value of urinary peptidoma analysis during lupus nephropathy The study of the urinary peptidome could make it possible to refine the indications of renal biopsy in the renal involvement of the lupus
In addition there is an increased cardiovascular risk in patients with chronic renal failure CKD Our team has demonstrated that the uremic toxins that accumulate in the IRC patients are agonists of the AhR transmission factor and induce endothelial dysfunction with development of a pro-thrombotic 15 and pro-inflammatory phenotype 16 During lupus or vasculitis at ANCA the risk of cardiovascular complications increases as renal function deteriorates 1718 while in parallel the risk of immunological outbreak of the disease decreases 1918 20 The investigators believe that activation of AhR by uremic toxins may be involved both in increasing the cardiovascular risk of these patients and in inhibiting the autoimmune response
There is therefore a strong rationale for studying the links between kidney disease immunity and cardiovascular complications
The expected results are the identification of new blood transcriptomic and urinary peptidomic biomarkers for diagnostic and prognostic purposes during renal disease NephroMIC will also provide research fellowships on biomarkers during renal disease especially during systemic diseases with renal involvement The NephroMIC collection will also allow participation in collaborative Nephrology research projects
a risk of renal insufficiency which depends on the severity of the attack the delay in the initiation of treatment and the possible occurrence of relapses which may leave fibrous sequelae and lead to the development of insufficiency chronic renal disease CKD
a risk of immunosuppression and infectious complications linked to the renal insufficiency itself or to the toxicity of immunosuppressive treatments aimed at controlling renal disease
an increased risk of cardiovascular complications linked on the one hand to the activity of the systemic disease and to the endothelial dysfunction it may entail and on the other hand to the cardiovascular risk associated with the IRC
Systemic lupus erythematosus SLE is a chronic autoimmune disease evolving in relapses interrupted by periods of remission Renal impairment of SLE is common 20-30 of patients in Europe 1 and severe 2 with an impact on patient survival 3 and a risk of progression to chronic renal insufficiency IRC Thus nearly 40 of patients with severe form develop IRC 4 and 5-10 have terminal IRC at 10 years 56 The classification of renal involvement according to the International Society of Nephrology Renal Pathology Society ISN RPS 7 distinguishes active proliferative forms requiring immunosuppressive therapy 8 nonproliferative or purely chronic forms However renal biopsy remains an invasive procedure 9 which can hardly be repeatedly performed let alone pre-emptively although the onset of tissue damage precedes the emergence of clinically detectable proteinuria 10 In addition the response of proliferative lupus nephropathy to immunosuppressive therapy is difficult to predict The progression in treatment is favorable in 70 to 80 of patients with proliferative form but 20-30 are refractory to the standard treatment while others retain important chronic lesions leading to chronic renal insufficiency
There is therefore a crucial need for non-invasive biomarkers to identify lupus patients at risk for developing renal disease and to predict the severity of histological involvement and response to immunosuppressive therapy
The investigators believe that the pathophysiological complexity of lupus nephropathy can not be summarized to a single biomarker and that a global omic approach could capture this complexity or identify new pathways
The blood transcriptome study is a non-invasive and usable approach in clinical research which allowed 10 years ago to identify the signature of lupus interferon IFN 11 which had not been detected in serum of patients and led to new therapeutic pathways The complexity and size of pan-genomic transcriptomic data may be an obstacle to their analysis and interpretation 12 Using a modular approach to reduce the size of transcriptomic blood glucose data and facilitate their interpretation the investigators were able to show the gradation of the interferon signature during lupus 13 and describe the link between neutrophil modular signature and renal impairment of lupus 14
In addition the search for noninvasive urinary biomarkers to avoid or limit biopsy indications in the NL or to predict the response to IS treatment to early adapt the intensity is of great interest The current PeptiduLUP study is being conducted to determine the diagnostic and prognostic value of urinary peptidoma analysis during lupus nephropathy The study of the urinary peptidome could make it possible to refine the indications of renal biopsy in the renal involvement of the lupus
In addition there is an increased cardiovascular risk in patients with chronic renal failure CKD Our team has demonstrated that the uremic toxins that accumulate in the IRC patients are agonists of the AhR transmission factor and induce endothelial dysfunction with development of a pro-thrombotic 15 and pro-inflammatory phenotype 16 During lupus or vasculitis at ANCA the risk of cardiovascular complications increases as renal function deteriorates 1718 while in parallel the risk of immunological outbreak of the disease decreases 1918 20 The investigators believe that activation of AhR by uremic toxins may be involved both in increasing the cardiovascular risk of these patients and in inhibiting the autoimmune response
There is therefore a strong rationale for studying the links between kidney disease immunity and cardiovascular complications
The expected results are the identification of new blood transcriptomic and urinary peptidomic biomarkers for diagnostic and prognostic purposes during renal disease NephroMIC will also provide research fellowships on biomarkers during renal disease especially during systemic diseases with renal involvement The NephroMIC collection will also allow participation in collaborative Nephrology research projects
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