Journal article
Endothelial cell autoantibodies in predicting declining renal function, end-stage renal disease, or death in adult type 2 diabetic nephropathy
Frontiers in endocrinology (Lausanne), Vol.5, 128
01/01/2014
DOI: 10.3389/fendo.2014.00128
PMCID: PMC4127944
PMID: 25157242
Abstract
Albuminuria is a strong predictor of diabetic nephropathy chronic kidney disease outcomes. Yet, therapeutic albuminuria-lowering has not consistently translated into a reduction in clinical events suggesting the involvement of additional pathogenic factors. Our hypothesis is that anti-endothelial cell autoantibodies play a role in development and progression in diabetic nephropathy. We determined anti-endothelial cell antibody (AECA) bioactivity in protein A-elutes of baseline plasma in 305 participants in the VA NEPHRON-D study, a randomized trial of angiotensin receptor blocker (ARB) or dual ARB plus angiotensin-converting enzyme inhibitor therapy in type 2 diabetes with proteinuric nephropathy. Thirty-eight percent (117/305) of participants had significantly reduced endothelial cell survival (<80%) in the IgG fraction of plasma. A VA NEPHRON-D primary endpoint [end-stage renal disease (ESRD), significant reduction in estimated glomerular filtration rate, or death] was experienced by 58 individuals. In adjusted Cox regression analysis, there was a significant interaction effect of baseline anti-endothelial cell-mediated cell survival and albuminuria on the hazard rate (HR) for primary composite endpoint (P=0.017). Participants lacking strongly inhibitory antibodies with albuminuria >= 1 g/g creatinine had a significantly increased primary event hazard ratio, 3.41 - 95% confidence intervals (CI 1.84-6.33; P< 0.001) compared to those lacking strongly inhibitory antibodies with lower baseline albuminuria (<1 g/g creatinine). These results suggest that anti-endothelial cell antibodies interact significantly with albuminuria in predicting the composite endpoint of death, ESRD, or substantial decline in renal function in older, adult type 2 diabetic nephropathy.
Details
- Title: Subtitle
- Endothelial cell autoantibodies in predicting declining renal function, end-stage renal disease, or death in adult type 2 diabetic nephropathy
- Creators
- Mark B. Zimering - VA New Jersey Health Care SystemJane H. Zhang - VA Connecticut Healthcare SystemPeter D. Guarino - VA Connecticut Healthcare SystemNicholas Emanuele - Veterans Health AdministrationPeter A. McCullough - Baylor Jack and Jane Hamilton Heart and Vascular HospitalLinda F. Fried - Veterans Health AdministrationVA NEPHRON-D Investigators
- Contributors
- B Dixon (Contributor) - University of Iowa, Nephrology
- Resource Type
- Journal article
- Publication Details
- Frontiers in endocrinology (Lausanne), Vol.5, 128
- DOI
- 10.3389/fendo.2014.00128
- PMID
- 25157242
- PMCID
- PMC4127944
- NLM abbreviation
- Front Endocrinol (Lausanne)
- ISSN
- 1664-2392
- eISSN
- 1664-2392
- Publisher
- Frontiers Media Sa
- Number of pages
- 7
- Grant note
- Veterans Biomedical Research Institute, East Orange, NJ, USA Cooperative Studies Program of the Department of Veterans Affairs, Office of Research and Development, Washington, DC
- Language
- English
- Date published
- 01/01/2014
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359674902771
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