Ignite Creation Date:
2024-05-05 @ 9:29 PM
Last Modification Date:
2024-10-26 @ 10:05 AM
Study NCT ID:
NCT00897715
Status:
COMPLETED
Last Update Posted:
2019-10-01
First Post:
2009-05-08
Brief Title:
Inflammation in Chronic Kidney Disease and Cardiovascular Disease - The Role of Genetics and Interleukin-1 Receptor Antagonist IL-1ra
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Inflammation in CKD and CVD - The Role of Genetics and IL-1ra
Status:
COMPLETED
Status Verified Date:
2019-09
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:
None
Brief Summary:
There has been an exponential growth in the number of people with Chronic Kidney Disease CKD needing dialysis or transplantation increasing from 209000 in 1991 to 472000 in 2004 This is highly concerning due to both the human cost and the burden that it represents to the health care system Recent comparison of the NHANES surveys showed that CKD prevalence increased from 10 in 1988-1994 to 13 in 1999-2004 Patients with CKD are more likely to die from premature cardiovascular death than to reach ESRD In those that reach ESRD cardiovascular disease CVD accounts for over half of the deaths in dialysis The prevalence of CKD for the VA population is 20 and 316 for diabetics higher than in the general population These observations emphasize the need of risk stratification early detection and prevention efforts with respect to CKD progression and the CVD burden that afflicts CKD through targeted interventions in high-risk groups personalized medicine
CKD is multifactorial however familial aggregation of end-stage renal disease ESRD and CKD have been reported for all types of nephropathy underscoring kidney disease genetic susceptibility Genetic predisposition to ESRD is stronger in African Africans African Americans with a first-degree relative with ESRD have a 9-fold increase risk of ESRD vs a 3-5 fold increase in whites
Studies consistently show that CKD is an inflammatory process and that biomarkers of inflammation increase since early stages of CKD CVD is also an inflammatory process and genes that affect inflammation are associated with higher risk of CVD Since inflammation is a common denominator of both disease processes CKD and CVD it is likely that genes that govern inflammation may be involved in both the predisposition to CKD and the burden of CVD attributable to CKD Additionally if inflammation plays a central role in the burden of CVD in CKD than drugs that modulate inflammation should impact both CKD progression and non-traditional CV risk factors and CVD
The overall goal of this proposal is to study genetic predisposition to CKD and CVD risk in CKD through inflammatory pathways and the effect that a potent anti-inflammatory intervention like interleukin 1 receptor antagonist IL-1ra will have in inflame patients with CKD stages 34 Specific Aims 1 To determine if specific polymorphismhaplotypes genotype combinations and gene-environmental interactions that can affect inflammation available from the Third National Health and Nutrition Examination Survey DNA data set specifically in the CRPIL-1 IL-10 and TNF- genes are associated with CKD 2 To determine if the specific polymorphisms and haplotypes studied in Aim 1 are associated with faster CKD progression and CV outcomes in a longitudinal cohort from the African American Study of Kidney Disease 3To determine if a targeted anti-inflammatory intervention an IL-1 receptor antagonist will modulate systemic inflammation endothelial function oxidative stress and urinary cytokines the proposed surrogate markers of CVD and CKD progression in inflame patients with CKD stages 34
CKD is multifactorial however familial aggregation of end-stage renal disease ESRD and CKD have been reported for all types of nephropathy underscoring kidney disease genetic susceptibility Genetic predisposition to ESRD is stronger in African Africans African Americans with a first-degree relative with ESRD have a 9-fold increase risk of ESRD vs a 3-5 fold increase in whites
Studies consistently show that CKD is an inflammatory process and that biomarkers of inflammation increase since early stages of CKD CVD is also an inflammatory process and genes that affect inflammation are associated with higher risk of CVD Since inflammation is a common denominator of both disease processes CKD and CVD it is likely that genes that govern inflammation may be involved in both the predisposition to CKD and the burden of CVD attributable to CKD Additionally if inflammation plays a central role in the burden of CVD in CKD than drugs that modulate inflammation should impact both CKD progression and non-traditional CV risk factors and CVD
The overall goal of this proposal is to study genetic predisposition to CKD and CVD risk in CKD through inflammatory pathways and the effect that a potent anti-inflammatory intervention like interleukin 1 receptor antagonist IL-1ra will have in inflame patients with CKD stages 34 Specific Aims 1 To determine if specific polymorphismhaplotypes genotype combinations and gene-environmental interactions that can affect inflammation available from the Third National Health and Nutrition Examination Survey DNA data set specifically in the CRPIL-1 IL-10 and TNF- genes are associated with CKD 2 To determine if the specific polymorphisms and haplotypes studied in Aim 1 are associated with faster CKD progression and CV outcomes in a longitudinal cohort from the African American Study of Kidney Disease 3To determine if a targeted anti-inflammatory intervention an IL-1 receptor antagonist will modulate systemic inflammation endothelial function oxidative stress and urinary cytokines the proposed surrogate markers of CVD and CKD progression in inflame patients with CKD stages 34
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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