The association of receptor of advanced glycated end products and inflammatory mediators contributes to endothelial dysfunction in a prospective study of acute kidney injury patients with sepsis Nermin A. H. Sadik • Waleed A. Mohamed • Mohamed I. Ahmed Received: 11 May 2011 / Accepted: 19 July 2011 / Published online: 3 August 2011 Ó Springer Science+Business Media, LLC. 2011 Abstract The pathogenesis of acute kidney injury (AKI) occurring due to sepsis is incompletely understood. Endo- thelial activation, defined as up-regulation of adhesion molecules by proinflammatory cytokines, may be central to the development of sepsis-induced AKI. Our aim was to determine levels of circulating adhesion molecules endo- thelial (E)-selectin, intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM), inflammatory mediators; tumor necrosis factor-a (TNF-a) and transform- ing growth factor-b (TGF-b), vasoactive mediators; endo- thelin-1 (ET-1) and nitric oxide (NO), soluble receptor for advanced glycated end products (sRAGE) and serum fetuin- A in septic AKI patients before and after antibiotic therapy. Nineteen AKI patients with sepsis and fifteen healthy con- trols were enrolled in this prospective study. Results revealed that 12 weeks of therapy caused amelioration of endothelial and inflammatory injuries as well as renal function markers. Moreover, the positive correlations between levels of RAGE and E-selectin (r = 0.88), ET-1 (r = 0.90), and TNF-a (r = 0.94) and negative with NO (r =-0.75–0.95) suggest that possible interaction of RAGE and inflammation may contribute to endothelial dysfunction in septic AKI patients. Keywords Acute kidney injury Á Endothelial damage Á Inflammation Á RAGE Abbreviations AKI Acute kidney injury ARF Acute renal failure GFR Glomerular filtration rate ICU Intensive care unit ICAM-1 Intercellular adhesion molecule VCAM-1 Vascular cell adhesion molecule TNF-a Tumor necrosis factor-a LPS Lipopolysaccharide WBC White blood count TGF-b Transforming growth factor-b ET-1 Endothelin-1 NO Nitric oxide RAGE Receptor for advanced glycated end products s Soluble IL Interleukin IRI Ischemia–reperfusion injury iNOS Inducible NO synthase eNOS Endothelial NO synthase PGI 2 Prostacyclin CRP C-reactive protein HMGB1 High-mobility group box 1 Introduction Acute kidney injury (AKI), previously called acute renal failure (ARF) [1], is an abrupt rapid loss of kidney func- tion. Its causes are numerous and include low blood Electronic supplementary material The online version of this article (doi:10.1007/s11010-011-1001-4) contains supplementary material, which is available to authorized users. N. A. H. Sadik (&) Faculty of Pharmacy, Biochemistry Department, Cairo University, Kasr El-Eini Street, Cairo 11562, Egypt e-mail: nerminsadik@yahoo.com W. A. Mohamed Chemistry Department, Kasr Eleini Teaching Hospitals, Cairo University, Cairo, Egypt M. I. Ahmed Nephrology Department, Kasr Eleini Teaching Hospitals, Cairo University, Cairo, Egypt 123 Mol Cell Biochem (2012) 359:73–81 DOI 10.1007/s11010-011-1001-4