Clinical relevance of hemodialysis-associated induction of cytokines

Water for dialysis and bicarbonate dialysate are regularly contaminated with 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-molecular-weight substances of bacterial origin (pyrogens) derived from contaminated dialysate are able to penetrate intact dialyzer membranes and to induce the production and release of proinflammtory cytokines in circulating mononuclear cells. Because complement enhances pyrogen-induced cytokine production, 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 hemodialysis-associated induction of IL-1 beta and TNF alpha are elevated plasma levels 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 addition, there are chronic inflammatory diseases associated with long-term hemodialysis therapy in which proinflammatory mediators such as IL-1 beta and TNFa are thought to play an important role. These diseases include beta 2-M amyloidosis, catabolic muscle protein degradation, and possibly also arteriosclerosis. The goal in modern hemodialysis therapy should be to reduce treatment-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.