We investigated the effect of dialysate ultrafiltration on the content of IL-l receptor antagonist (IL-1Ra) in mononuclear cells (PBMC) as a marker of the inflammatory response. 11 patients on Cuprophan dialyzers were randomly assigned to treatment with standard bicarbonate dialysate first and then to ultrafiltered dialysate or the reverse order in a crossover design. In each treatment period (at least 4 weeks) weekly separations of PBMC were performed before the start of dialysis. Cellular content of IL-1Ra was determined in PBMC that were frozen immediately after separation; all values of IL-1Ra in each treatment period were averaged. The dialysate contained a median of 148 (range, 61-400) colony-forming units without dialysate filter; no bacterial growth was detected in ultrafiltered dialysate. The median endotoxin content was 80 pg/ml in nonfiltered dialysate; endotoxin was below 5 pg/ml in all ultrafiltered dialysate samples. Cellular content of IL-1Ra decreased in all but 1 patient with the use of ultrafiltered dialysate (mean ± SEM: 1,4676± 113 pg/ml without dialysate filter vs. 1,166 ± 104 pg/ml with filter, p = 0.016). The present study demonstrates that the bacterial contamination of the dialysate induces a systemic inflammatory response in hemodialysis patients.
These data suggest penetration of cytokine-inducing substances through both cellulosic and synthetic dialysers. Differences between dialysers may exist regarding extent and time course of penetration. The detection of cytokine mRNA as well as the measurement of IL-1Ra synthesis is a more sensitive marker for the transfer of cytokine-inducing substances through dialyser membranes than the measurement of IL-1 beta protein synthesis.
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