In the steady state after a run-in phase of 3 months, the acute effects of 3 modifications of weekly heparin-induced extracorporeal LDL precipitation (HELP) were studied in 5 ESRD and 2 non-uremic hypercholesterolemic coronary patients. In ESRD patients (n = 29 sessions), HELP reduced LDL-cholesterol (LDL-C) (56 +/- 7%) and fibrinogen (FIB) (54 +/- 10%) by a similar percentage as compared to non-uremic controls (60 +/- 4% and 61 +/- 3%, resp.; n = 5). In order to eliminate the need for extra HELP sessions in addition to the normal dialysis regimen, newly developed hardware was then used to perform combined synchronous HELP/HD (n = 12). However, premature precipitate filter plugging probably due to hyperfibrinogenemia in ESRD patients, accentuated by ultrafiltration (UF), decreased the corresponding reductions to 26 +/- 9% (LDL-C) and 34 +/- 11% (FIB). Therefore, the procedure was modified by reversing the filtrate flux through the precipitate filter membrane after 900 ml of treated plasma ("reverse flux filtration", RFF; n = 11). Thus, in RFF-HELP/HD the LDL/FIB/heparin coprecipitate was deposited on both filter membrane sides which caused a significant enhancement of the filter capacity and improved reductions to 46 +/- 14% for LDL-C and 51 +/- 15% for FIB. Elution of the precipitate from the precipitate filter after the sessions showed that RFF-HELP/HD had trapped 1733 +/- 238 mg LDL-C and 8108 +/- 1876 mg FIB in ESRD patients, while HELP eliminated 1890 +/- 333 mg LDL-C and only 3663 +/- 369 mg FIB in non-uremics. Filter precipitate recoveries (relative to the mass removed from the patient plasma pool) amounted to 97 +/- 18% for LDL-C and 158 +/- 67% for FIB in the ESRD group treated by RFF-HELP/HD vs. 70 and 76% in the non-uremic HELP group. Probably, passive transport of lipoproteins and FIB from the interstitium into the vascular space caused repletion of this compartment during HELP/HD where an UF induced solvent drag is effective. In summary, the new RFF-HELP/HD procedure effectively reduced LDL-C and FIB in ESRD patients who could not be adequately treated by the conventional HELP/HD system.