Diffusive and convective transfer of cytokine-inducing bacterial products across hemodialysis membranes

Abstract

The widespread use of bicarbonate dialysate, and high-flux and high-efficiency dialyzers have raised concerns regarding the transmembrane passage of bacterial products from the dialysate into the blood compartment. To study the mechanisms as well as magnitude of the transmembrane transfer of bacterial products from the dialysate, we developed a computerized in vitro dialysis model which provides continuous pressure recording from the arterial, venous, dialysate inflow and outflow ports. By virtue of a computer controlled on-line infusion pump, this model permits control of ultrafiltration/backfiltration. Heparinized (10 U/ml) whole blood (150 ml) was circulated through the blood compartment for 120 minutes at 100 ml/min. Bicarbonate dialysate contaminated with Pseudomonas maltophilia filtrate was circulated through the dialysate compartment at 100 ml/min. A two-point pressure of -10 mm of Hg (ultrafiltration) was maintained for the first 60 minutes and -10 mm of Hg (backfiltration) for the next 60 minutes. Whole blood samples (10 ml) were drawn from the blood at 0, 60 and 120 minutes. Peripheral blood mononuclear cells (PBMC) harvested from these samples were incubated for 24 hours in tissue culture medium. In addition, 0.5 ml samples of dialysate were collected at 0, 60 and 120 minutes and incubated with PBMC from the same donor for 24 hours. After 24 hour incubation, total cell-associated IL-1Ra and IL-1 beta were measured by specific radioimmunoassay. Paired experiments were performed with eight high-flux synthetic membranes (polyamide) and eight low-flux cellulose membranes (hemophan). Cytokine production is expressed as pg/2.5 million PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)