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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

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Abstract

The pathogenesis of acute kidney injury (AKI) occurring due to sepsis is incompletely understood. Endothelial 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 endothelial (E)-selectin, intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM), inflammatory mediators; tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), vasoactive mediators; endothelin-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 controls 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-α (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.

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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-α:

Tumor necrosis factor-α

LPS:

Lipopolysaccharide

WBC:

White blood count

TGF-β:

Transforming growth factor-β

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

PGI2 :

Prostacyclin

CRP:

C-reactive protein

HMGB1:

High-mobility group box 1

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Acknowledgments

The authors gratefully acknowledge the financial assistance provided by Faculty of Pharmacy, Cairo University, Cairo, Egypt. We gratefully acknowledge Nephrology department, Faculty of Medicine, Cairo University.

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The authors declare that there are no conflict of interest.

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Authors and Affiliations

  1. Faculty of Pharmacy, Biochemistry Department, Cairo University, Kasr El-Eini Street, Cairo, 11562, Egypt

    Nermin A. H. Sadik

  2. Chemistry Department, Kasr Eleini Teaching Hospitals, Cairo University, Cairo, Egypt

    Waleed A. Mohamed

  3. Nephrology Department, Kasr Eleini Teaching Hospitals, Cairo University, Cairo, Egypt

    Mohamed I. Ahmed

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  1. Nermin A. H. Sadik
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  2. Waleed A. Mohamed
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  3. Mohamed I. Ahmed
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Correspondence to Nermin A. H. Sadik.

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Sadik, N.A.H., Mohamed, W.A. & Ahmed, M.I. 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. Mol Cell Biochem 359, 73–81 (2012). https://doi.org/10.1007/s11010-011-1001-4

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