The concept of regeneration of dialysis fluids and of ultrafiltrate in part
icular has been recently revisited. Hemodiafiltration with online regenerat
ion of the ultrafiltrate allows the concomitant infusion of sodium, calcium
, and bicarbonate. Here, we studied the adsorptive characteristics of an in
tegrated two-step sorbent system relative to different solutes present in t
he ultrafiltrate: sodium, calcium, phosphate, bicarbonate, uric acid, creat
inine, and beta(2)-microglobulin. In vitro studies were performed in order
to differentiate the relative roles for each sorbent (mineral-activated cha
rcoal or hydrophobic resin) in adsorbing st given solute. Ex vivo studies w
ere performed in order to evaluate the presence of cytokines (interleukin-1
beta and tumor necrosis factor-alpha), of cytokine (interleukin-1 beta and
tumor necrosis factar-alpha)-inducing activities, and of the cytokine rele
ase in response to exogenous bacterial lipopolysaccharide by normal whole b
lood incubated with ultrafiltrate samples obtained at 15, 120, and 240 minu
tes after the start of treatment. The results of the present studies show t
he presence of immunomodulatory substances in the ultrafiltrate and the sig
nificant (P < 0.01) increase in the lipopolysaccharide-induced release of b
oth interleukin-1 beta and tumor necrosis factor-alpha. The biological rele
vance of the ultrafiltrate and the possible relevance of the online, endoge
nous reinfusion are discussed.