AUTHOR=Zimering Mark , Zhang Jane H., Guarino Peter , Emanuele Nicholas , McCullough Peter , Fried Linda TITLE=Endothelial cell autoantibodies interact with albuminuria in predicting declining renal function, end-stage renal disease or death in adult type 2 diabetic nephropathy JOURNAL=Frontiers in Endocrinology VOLUME=5 YEAR=2014 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2014.00128 DOI=10.3389/fendo.2014.00128 ISSN=1664-2392 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 (