Hepatoactive substances eliminated by continuous venovenous hemofiltration in acute renal failure patients. Background Acute renal failure (ARF) in critically ill patients is mostly part of a multi-organ failure. Therefore, the effects of renal replacement therapy on the liver are clinically important. We investigated the effects of ultrafiltrates of patients treated with continuous venovenous hemofiltration (CVVH) on liver cells in vitro. Methods. Patients with ARF were consecutively treated with CVVH using Multiflow60 (group I) or FH66 filters (group II). They were comparable with respect to diagnosis, age, sex, laboratory parameters, and renal replacement treatment, but were different in daily diuresis, serum levels, and blood flow. Ultrafiltrates were collected within the first 10 minutes after change of hemofilter. Proliferation (bromodeoxyuridine), vitality (lactate dehydrogenase), and acute-phase protein secretion of HepG2 cells were measured. Results. Ultrafiltrates changed liver cell function significantly compared with medium control. Proliferation (group I 29.8 +/- 5.2% vs. group II 48.4 +/- 6.6%, P < 0.05) and vitality (group I 78.7 +/- 2.0% vs. group II 87.6 +/- 1.7%, P < 0.01) of HepG2 cells were significantly different. On the one hand, the secretion of the negative acute-phase protein transferrin [group I 3.1 +/- 0.2 (ng/mu g protein) vs. group II 5.1 +/- 0.5 (ng/mu g protein), P < 0.01] was significantly reduced by MultiflowGO ultrafiltrates. On the other hand, positive acute-phase protein al-acid glycoprotein was significantly stimulated by MultiflowGO ultrafiltrates [group I 2.6 +/- 0.1 (ng/mu g protein) vs. group II 1.7 +/- 0.1 (ng/mu g protein), P < 0.001]. Conclusion. This study demonstrates hepatoactive mediators in the ultrafiltrates. They are hepatotoxic and influence acute-phase protein metabolism. Further studies have to elucidate the different effects in both groups and the analysis of the putative mediator(s). It remains a challenging task to consider therapeutic measures to optimize renal replacement therapy in critically ill patients.