Clinical relevance of hemodialysis-associated induction of cytokines

Water for dialysis and bicarbonate dialysate are regularly contaminated wit h Gramnegative bacteria, endotoxin and other bacterial products. The degree of contamination exceeds recommended standards of dialysate quality in 20% of tested samples. Several in vitro studies have demonstrated that small-m olecular-weight substances of bacterial origin (pyrogens) derived from cont aminated dialysate are able to penetrate intact dialyzer membranes and to i nduce the production and release of proinflammtory cytokines in circulating mononuclear cells. Because complement enhances pyrogen-induced cytokine pr oduction, the risk of hemodialysis-associated cytokine induction is highest when contaminated dialysate is used in combination with pyrogen-permeable and complement-activating dialyzer membranes. Acute consequences of hemodia lysis-associated induction of IL-1 beta and TNF alpha are elevated plasma l evels of acute-phase-proteins (such as CRP), prostaglandins (such as PGE(2) ) and NO, which dependent on the magnitude of the acute-phase response may induce fever, cardiovascular instability and edema (lung edema). In additio n, there are chronic inflammatory diseases associated with long-term hemodi alysis therapy in which proinflammatory mediators such as IL-1 beta and TNF a are thought to play an important role. These diseases include beta 2-M am yloidosis, catabolic muscle protein degradation, and possibly also arterios clerosis. The goal in modern hemodialysis therapy should be to reduce treat ment-dependent cytokine induction by improving the bacteriological quality of dialysate. It is hoped that thereby dialysis-associated diseases will be less severe or even prevented.