REMOVAL OF CONSTITUTIVE AND INDUCIBLE NITRIC-OXIDE SYNTHASE-ACTIVE COMPOUNDS IN A MODIFIED HEMODIAFILTRATION WITH ONLINE PRODUCTION OF SUBSTITUTION FLUID - THE CONTRIBUTION OF CONVECTION AND DIFFUSION

Chronic renal failure and the uremic state lead to accumulation of var ious endogenous inhibitors of nitric oxide synthase. Previous studies on end-stage uremic patients nitric oxide synthase activity in murine vascular endothelium and cytokine-induced macrophage cell lines was sh own to be modulated during treatment (Nephrol Dial Transplant 1995; 10 : 1386-96). Paired filtration dialysis, a modified hemodiafiltration t echnique, physically separates convection from diffusion. Plasmas, ult rafiltrates and dialysates from seven uremic patients undergoing paire d filtration dialysis performed using ultrapure apyrogen substitution fluid in the absence (first 120 min) or presence (last 120 min) of ext racellular fluid reduction were tested for their inhibitory/stimulator y effect on ecNOS, constitutively expressed on t.End 1 cell line, a mu rine vascular endothelium, or for their inducing effect on iNOS, induc ible on J774 cells, a macrophage cell line. On ecNOS, Group 1 (stimula tory, 3/7 patients) markedly enhanced the ecNOS activity as compared t o control plasma, whereas group 2 plasma (inhibitory, 4/7 patients) in hibited ecNOS plasma. Post-dialysis plasma samples from all Group 1 an d 2 patients showed a marked decrease of the predialysis stimulatory a nd inhibitory activity, respectively. On iNOS: all patient plasmas sti mulated iNOS activity The UF and particularly the dialysate had a rema rkable iNOS inducing effect (Group 1). The substitution fluid obtained at 120 min during treatment in Group 1 and 2 had no effect on NOS act ivity No correlation was found between predialysis ecNOS or iNOS activ ity values with mean systolic or diastolic pressures. These studies su ggest a complex balance of ecNOS inhibitors/stimulators and iNOS induc ers in uremia. Dialysis may remove ecNOS inhibitors and stimulators by convection and, in the latter case, by diffusion. iNOS inducers are r emoved during dialysis, suggesting the biocompatibility of the dialysi s system with the on-line production of ultrapure substitution fluid.