Impact of Continuous Hemofiltration on Cytokines and Cytokine Inhibitors in Oliguric Patients Suffering from Systemic Inflammatory Response Syndrome

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Abstract
The impact of continuous hemofiltration (CHF) using a polyacrylonitrile membrane on the kinetics of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-lβ), and their inhibitors (soluble TNF receptors [sTNFrl, sTNFrII], interleukin-1 receptor antagonist [IL-1Ra]) was assessed in nine oliguric patients suffering from systemic inflammatory response syndrome. Blood and plasma flow (Qb, Qp), sieving coefficient (SC), plasma and ultrafiltrate clearances (Kp, Kuf), and plasma extraction rates (ERp) were calculated at different time points using standard formulas. No significant improvement of hemodynamics or gas exchange was noted following HF but a significant increase in serum bicarbonate occurred after 24 h (P < 0.05). TNFα was detected in plasma from all patients (153 ± 2.3 pg/mL [mean ± SEM]). None of the patients had detectable IL-1β levels. High levels of the TNF receptors (sTNFrl 20.338 ± 2.431 pg/mL; sTNFrII 17.839 ± 2.630 pg/mL) and IL-1Ra (19.775 ± 3.943 pg/mL) were found in all patients. Upon initiation of hemofiltration (HF), the mean individual sTNFrl/TNFα. ratio amounted to 269 ± 84.6 and the sTNFrII/TNFα ratio to 249 ± 91.8. Mean ultrafiltrate volume (Vuf) was 11.8 ± 0.4 L/day. Appreciable sieving of IL-1Ra (SC 0.45 ± 0.10), but not of the other cytokines, was noted (SC TNFα, sTNFrI, sTNFrII < 0.09). Despite minimal Kuf of TNFα, sTNFrI, and STNFrII (Kuf < 0.8 mL/min), appreciable Kp was noted, suggesting that membrane adsorption occurs (Kp ≈ 8 mL/min). There was a nonsignificant increase of the ratios between both TNF receptors and TNFα across the filter (sTNFrI/TNFα ratio [pre] 231 ± 37.9 versus [post] 312 ± 75.3); sTNFrII/TNFα ratio [pre] 211 ± 42.1 versus [post] 291 ± 79.3). Appreciable Kp of IL-1Ra was noted (Kp 17.3 ± 1.61 mL/min), which was only in part due to Kuf(4.0 ± 0.86 mL/min). There was a significant decrease of IL-1Ra levels across the membrane, both overall ([pre] 20.223 ± 2.282 versus [post] 16.637 ± 2.039 pg/mL; P < 0.01) and at different time points (P < 0.01). Only for IL-1Ra was significant extraction from plasma noted (ERp 26 ± 6.0%). Plasma levels of TNFα, sTNFrI, sTNFrII, and IL-1Ra were not altered by 24 h of CHF. In conclusion, both cytokines and cytokine inhibitors can be removed from the circulation, either by convective transport or by membrane adsorption. Using low-volume HF (Vuf 12 L/day), no impact on cytokine plasma levels nor the patients hemodynamics or gas exchange was noted. The appreciable SC of IL-1Ra (0.45), however, suggests that HF with high(er) UF volumes (>50 L/day) may be able to achieve reductions in plasma levels of some peptide (anti)mediators. However, whether this aspecific elimination of both mediators and antimediators may alter the clinical course in critically ill patients remains to be investigated.