Inflammation and atherosclerosis in end-stage renal disease.
Atherosclerosis is a multifaceted process which may be initiated by various insults to vascular endothelium. Independently of the nature of the offending factor, the endothelial dysfunction that results from the initial insult is characterized by increased adhesiveness of the endothelium to leukocytes and platelets and by the synthesis of vasoactive molecules, cytokines and procoagulant factors. This defensive response is characterized by classical inflammatory changes and may lead to plaque formation, luminal obstruction and plaque rupture. Factors involved in arterial damage in end-stage renal disease (ESRD) span from classical risk factors to disease-peculiar factors (anemia, secondary hyperparathyroidism and exposure to bioincompatible dialysis membranes and/or contaminated dialysis fluid) and to emerging and novel risk factors such as hyperhomocysteinemia, infections and accumulation of the endogenous inhibitor of NO synthase, asymmetric dimethylarginine (ADMA). There is strong and consistent evidence that acute phase reactants like C-reactive protein and cytokines like IL-beta, TNF-alpha and IL-6 are independently associated with death and atherosclerosis in ESRD patients. The experimental and epidemiological data collected thus far coherently show that endothelial dysfunction resulting from inflammation may promote abnormal vascular behavior and thrombosis in ESRD. There are several possible therapeutic approaches for reducing the risk excess associated with inflammation in ESRD. These possibilities range from drugs interfering with the angiotensin system or with adrenergic activity to anti-inflammatory and antilipid agents to vitamins, antioxidants, to the amino acid precursor of nitric oxide, L-arginine, and perhaps to antibiotics. The intellectual framework is well delineated but very few controlled trials have been performed or are underway in patients with ESRD.
Zoccali
Carmine
C
Consiglio Nazionale delle Ricerche (CNR) - IBM, Laboratorio CNR di Epidemiologia Clinica e Fisiopatologia delle Malattie Renali e dell'Ipertensione Arteriosa, Ospedali Riuniti, Reggio Calabria, Italia. carmine.zoccali@tin.it
Mallamaci
Francesca
F
Tripepi
Giovanni
G
D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000473:pathology; D012307:Risk Factors