Abstract 14782: Effect of CD40 and sCD40L on Renal Function and Survival in Patients with Renal Artery Stenosis
Introduction: Recent work suggests that an important mediator of renal fibrosis and inflammation may be activation of the CD40 receptor on the proximal tubular epithelium by soluble CD40 ligand (sCD40L) released by activated platelets. The role of CD40-sCD40L in patients with ischemic renal disease is unknown. Hypothesis: We assessed the hypothesis that circulating CD40 binds to sCD40L preventing its interaction with tissue bound CD40 resulting in an improvement in renal function.
Methods: Plasma levels of CD40 and sCD40L were measured by enzyme linked immunosorbent assay in a single center cohort of 60 patients with renal artery stenosis recruited from Salford Royal Hospital, Manchester, UK. A natural log transformation of CD40 was performed to normalize the data. Estimated GFR was used as the primary indicator of renal function.
Results: By univariate analysis CD40 was the strongest predictor of changes in renal function with lower baseline levels of circulating CD40 significantly associated with a greater loss of kidney function at one year follow-up (p<0.03, Figure 1). Lower CD40 levels continued to be significantly associated with a decline in renal function when accounting for other factors using a multiple linear regression model (p<0.03, R2=0.15). Lower levels of baseline CD40 were associated with a trend towards worse survival (7.3 ± 0.9 pg/ml, n=48 vs. 6.7 ± 1.0 pg/ml, n=12, p=0.06).
Conclusions: The CD40/sCD40L signaling cascade may be a novel mechanism contributing to the development and progression of renal injury in patients with renal artery stenosis, and may effect survival. Figure 1. Regression plot of baseline CD40 with percent change in eGFR at one year follow up.
- © 2012 by American Heart Association, Inc.