Clinical and biochemical assessment of endothelial dysfunction and inflammation in renal transplant recipients

Introduction. Renal replacement therapy remains the treatment of option for patients in end stage renal disease. The most frequent cause of late allograft loss is cardiovascular disease, which constitutes the leading cause of death of renal transplant recipients (RTR). When compared with the general population, RTR show a four-fold greater risk for CVD, and a two-fold higher risk for cardiovascular death. Renal transplant dysfunction can be considered as a traditional risk factor, while high sympathetic activity and accumulation of the endogenous inhibitor of endothelial NO synthase (eNOS), asymmetric dimethylarginine (ADMA) are factors peculiar to chronic renal failure. eNOS can be strongly inhibited by ADMA, whose accumulation in plasma may play an important role in endothelial dysfunction. ADMA is an uremic toxin that can be considered as parameter of endothelial dysfunction. ADMA, also, causes local vasoconstriction when infused intra-arterially. Symmetric dimethylaginine (SDMA) does not inhibit NOS directly, and is also elevated in patients with renal failure, its levels, better than ADMA, correlate with glomerular filtration rate (GFR). ADMA was proposed to be a marker for atherosclerotic changes, and for the assessment of cardiovascular morbidity and mortality. Atherosclerosis is today described as a disease where inflammation is the dominant pathological and biochemical alteration. The development of the atherosclerotic plaque is closely linked to expression of different cellular adhesion molecules (CAMs), that are essential mediators, playing a central role in the recruitment of inflammatory cells to the site development. Many factors were demonstrated to increase concentration of cellular adhesion molecules: hypertension, immunosuppressive therapy, autoimmune disease and cell mediated allograft rejection. These CAMs can be measured in plasma and therefore may represent promising biomarkers that may reflect underlying endothelial activation and vascular inf