Patrick M. Honore

High-volume hemofiltration in sepsis and SIRS: current concepts and future prospects.

In recent years, a number of techniques have been studied and developed in the field of renal replacement therapy in the septic patient. Manipulation of ultrafiltrate dose, membrane porosity, mode of clearance, and combinations of techniques have yielded promising findings. However, at present, conclusive evidence based on well-designed, randomized controlled trials remains scarce, limiting the practical implementation of many techniques in daily practice outside the context of a study. From the few well-designed and documented studies that we have so far, it is safe to say that optimalization of delivered dose in renal replacement therapy has a proven positive effect. An ultrafiltration rate between 35 and 45 ml/kg/h, with adjustment for predilution and down time, can be recommended for the septic patient until other data are available. The results of further dose outcome studies with higher ultrafiltration rates will likely be the stepping stone to further improvements in daily clinical practice.

Are the synergistic effects of high-volume haemofiltration and enhanced adsorption the missing key in sepsis modulation?*

38. Canaud B, Mingardi G, Braun J et al. STRIATA Study Investigators. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study. Nephrol Dial Transplant 2008; 23: 3654–3661 39. Levin NW, Fishbane S, Cañedo FV et al. MAXIMA Study Investigators. Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet 2007; 370: 1415–1421 40. Sulowicz W, Locatelli F, Ryckelynck JP et al. Once-monthly subcutaneous C.E.R.A. maintains stable hemoglobin control in patients with chronic kidney disease on dialysis converted directly from epoetin one to three times weekly. Clin J Am Soc Nephrol 2007; 2: 637– 646 41. Spinowitz B, Coyne DW, Lok CE et al. RUBRA Study Investigators. C.E.R.A. maintains stable control of hemoglobin in patients with chronic kidney disease on dialysis when administered once every two weeks. Am J Nephrol 2008; 28: 280–289 42. Casadevall N, Nataf J, Viron B et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 2002; 346: 469–475 43. Hermeling S, Schellekens H, Crommelin DJ et al. Micelle-associated protein in epoetin formulations: a risk factor for immunogenicity? Pharm Res 2003; 20: 1903–1907 44. Bennett CL, Cournoyer D, Carson KR et al. Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin: a follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project. Blood 2005; 106: 3343–3347 45. Eckardt KU, Macdougall IC, Froissart M et al. Successful treatment of anti-erythropoietin antibody-mediated pure red cell aplasia with HematideTM. Nephrol Dial Transplant 2008; 1(Suppl 2): i216 (abstract) 46. Woodburn KW, Fan Q, Winslow S et al. Hematide is immunologically distinct from erythropoietin and corrects anemia induced by antierythropoietin antibodies in a rat pure red cell aplasia model. Exp Hematol 2007; 35: 1201–1208 47. FDA Briefing Document. Safety Concerns Associated with Aranesp (darbepoetin alfa) Amgen, Inc. and Procrit (epoetin alfa) Ortho Biotech, L.P., for the Treatment of Anemia Associated with Cancer Chemotherapy: Hearings before the Subcommittee on Oncologic Drugs Advisory Committee, Center for Drug Evaluation and Research. http://www.fda.gov/ohrms/dockets/ac/04/briefing/4037B2_ 04_ FDA-Aranesp-Procrit.htm#_ednref45 48. FDA Briefing Document. 10 May 2007: Oncologic Drugs Advisory Committee. Continuing reassessment of the risks of erythropoiesisstimulating agents (ESAs) administered for the treatment of anemia associated with cancer chemotherapy. http://www.fda.gov/ohrms/ dockets/ac/07/briefing/2007-4301b2-02-FDA.pdf

ACUTE KIDNEY INJURY IN THE ICU: TIME HAS COME FOR AN EARLY BIOMARKER KIT!

Abstract Early recognition of acute kidney injury (AKI) in the intensive care unit (ICU) remains a critical problem, with a rising incidence and a high mortality rate. As a consequence, the actual lack of an early and effective biomarker results in a significant delay in initiating appropriate therapy. The accurate diagnosis of AKI is especially problematic in critically-ill patients, in whom we know that renal function is in an unsteady state; therefore the validity of creatinine- based baseline assessment measures is reduced. Because the rationale for assessing AKI markers in critically-ill patients is strong at the present time, researchers are stimulated to establish a multidimensional AKI classification system. This system should in essence grade AKI severity. The most widely referenced classification is the RIFLE system. Thus, early recognition of AKI, well before changes in serum creatinine occur, has come under intensive research, because it is evidenced that even small increases in serum creatinine are associated with an increase in patient mortality. The development of a biomarker kit in which several early markers with different characteristics are combined, is essential. Multi-centre, randomized studies indicate a potential for early biomarkers able to diagnose AKI 48 hours before creatinine changes. In conclusion, time has come to leave serum creatinine behind as a marker of renal function in patients with AKI on the ICU. Only then will we be able to offer early goal-directed therapy for the kidney in the ICU setting.

Déficit acquis en Antithrombine et hemofiltration

Resume Introduction. — Lhemofiltration (HF) est frequente dans la prise en charge des patients en choc septique et peut se compliquer de thromboses precoces des filtres ( Materiel et methodes. — etude multicentrique, conduite de mars 2003 a mai 2004 sur deux centres hospitaliers (CHU et CHG) dans trois reanimations. 28 patients en choc septique ont ete inclus. Tous etaient traites par HF et anticoagules par de lheparine standard. LAT etait dosee avant le branchement en HF puis tous les jours, une supplementation etait mise en route apres deux thromboses precoces : Bolus (CHG) et perfusion continue (CHU). Resultats. — Le taux initial dAT est bas avec une mediane a 45,4 % (16 % – 69 %). La restauration dun taux superieur a 60 % permet lallongement de la duree de vie moyenne du filtre de 15,2 h a 33,2 h (p Discussion. — En HF dans le sepsis, la duree de vie du filtre est etroitement correlee au taux dAT, qui lorsquil est inferieur a 60 % represente un risque important de thrombose precoce du filtre. Une supplementation simple en AT permet une restauration de lactivite du couple HNF/AT et une augmentation dun facteur 2 de la duree de vie moyenne des filtres. La perfusion en continue semble preferable. Le rapport cout/efficacite du traitement reste cependant a evaluer.

Contents Vol. 35, 2013

230 Selected Abstracts from the 31th International Vicenza Course on Critical Care Nephrology Vicenza, June 11–14, 2013 (available online only)