Point of care measurement of plasma creatinine in critically ill patients with acute kidney injury.

We report the utility of an enzymatic point of care system for estimation of plasma creatinine concentration in critically ill patients with acute kidney injury. Multiple measurements were obtained from a heterogenous population admitted to a multi-disciplinary intensive care unit. The acute kidney injury network guidelines were used to identify and stratify patients based on the creatinine concentration. Central laboratory values were used as comparators to assess the precision and bias of the system. Overall, point of care measurements correlated well with central pathology results (R(2) = 0.991, p < 0.001), although there tended to be a small negative bias in patients with acute kidney injury (3 micromol x l(-1)). The accuracy of point of care measurement is within clinically acceptable limits and given the much shorter turn around time can be used to identify and monitor patients with acute kidney injury in the critical care environment.

[Rationale for the use of extracorporeal treatments for sepsis].

Sepsis is the leading cause of disability and mortality among critical patients; moreover, it causes high economic expenditures. Although very much is known about the pathophysiology of this condition and its mediators despite great investments directed to its control, mortality rates remain high. Recent treatment manuals emphasize the value of early goal-oriented therapy and also point to the high efficacy of activated protein C. Extracorporeal blood clearance may potentially become a new approach to treating this condition. There are reports on its positive clinical results that are likely associated with the effective removal of septic mediators. Human and animal studies, few and rather alike as they are, have yielded promising results. It is evident that the use of these procedures is justified; however, their efficiency in sepsis requires large-scale, correctly conducted studies.

First clinical trial for a new CRRT machine: the Prismaflex.

A new CRRT machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called "Prismaflex" (Gambro-Dasco, Mirandola, Modena) and it is the natural evolution of the Prisma machine that has been utilized worldwide for CRRT in the last decade. We performed a preliminary "alfa trial" to establish usability, flexibility and realiability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities. Forty-one runs were conducted on 13 patients and the difference between delivered and prescribed parameters was always lower than 2%. We concluded that the new Prismaflex is a well designed new machine for CRRT and can be safely and effectively utilized in the critical care nephrology setting.

Pulse high volume hemofiltration.

The sepsis syndrome is the most common cause of acute renal failure and multiple organ dysfunction in critically ill subjects and continues to have an alarmingly high mortality. Normal immune homeostasis is interrupted by a complex storm of inflammatory mediators responsible for the deleterious effects. Extracorporeal blood purification techniques can confer benefits in sepsis by proven non-specific removal of these mediators (pro- or anti-inflammatory), and provide a logical and adequate approach to treat this syndrome. High volume hemofiltration (HVHF) has had the most dramatic effect conferring benefits in hemodynamics, reduction in vasopressor doses and improvement in survival. "Pulse HVHF" is the latest approach which may offer the most efficient results: a daily schedule of 6-8 hours followed by standard CVVH. This paper describes the rationale and potential of this technique. Reliability and tolerance of this technique and biological effects are described.

Extracorporeal treatments in sepsis: are there new perspectives?

Sepsis continues to provide a major challenge to clinicians. Despite vast advancements achieved in the understanding of its pathways and mechanisms, the incidence of sepsis is increasing and the mortality and morbidity rates remain high, generating a considerable burden to health budgets worldwide. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the non-selective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extra-corporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials which lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. We will also review novel information related to other blood purification techniques using largo pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance.

Caspase-3 and -8 activation and cytokine removal with a novel cellulose triacetate super-permeable membrane in an in vitro sepsis model.

Pro-apoptotic molecules are generated during sepsis which may be responsible for alteration of organ function in sepsis. Removal of systemic apoptotic activity may affect recovery from sepsis. Current high flux membranes might not be sufficiently permeable to eliminate pro-apoptotic factors. We evaluated the elimination of pro-apoptotic factors induced by LPS in human whole blood by a super-permeable cellulose triacetate membrane (SUREFLUX FH 150, Nipro, Osaka, Japan) in comparison to a standard high flux cellulose triacetate membrane (UT 700, Nipro, Osaka, Japan) and a polyethersulfone plasmafilter (Bellco, Mirandola Italy) in an in vitro blood circulation. We spiked human whole blood with lipopolysaccharide from Escherichia coli (Serotype 026-86, 10 mg/ml), incubated it for 3 hours to allow cytokine generation and recirculated it at 300 ml/min for 3 hours. The UF line was first returned to the blood module at 10 min. After this, the UF was drained from 10 to 60 min at a rate of 1000 ml/h. Zero balance was obtained by re-infusion of bicarbonate buffered hemofiltration fluid. Apoptosis was assessed on U937 monocytes (incubated with plasma or ultrafiltrate) by fluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V flow cytometry. Caspase-3 and Caspase-8 activity was assessed on the recirculated blood monocytes by spectrophotometric methods. IL-2, IL-10 and TNFalpha were determined by commercially available ELISAs. Sieving coefficients and clearances were determined for the different cytokines. Caspase-3 and Caspase-8 were activated by LPS and remained either stable or increased during in vitro circulation. Apoptosis activity of U937 cells, when incubated with the ultrafiltrate, increased in parallel with arterial plasma values (for Uf: UT700 = 23.1%; Sureflux FH150 = 42.5%). However, by 60 min the apoptotic activity recorded with the ultrafiltrate was reduced to the levels of arterial plasma (for Uf: UT700 = 19.8%; Sureflux FH150 = 11.2%). Sieving coefficients in the super-permeable membrane were significantly higher for all measured cytokines in comparison to the standard high flux membrane (e.g. TNFalpha 0.72 vs 0.03 p < 0.001) and close to the values observed for the plasmafiltration membrane. Nevertheless protein losses measured by albumin leakage were much lower with the Sureflux filter in comparison to the plasmafilter. In conclusion, pro-apoptotic factors can be eliminated by dialytic membranes with the removal rate maximized by using super high flux dialysers which may represent a compromise between hemofiltration and plasmafiltration membranes.

Effects of novel manufacturing technology on blood and dialysate flow distribution in a new low flux "alpha Polysulfone" hemodialyzer.

The main target for low flux hemodialyzers is an efficient low molecular weight solutes clearance. Such efficiency is largely dependent on the optimization of diffusion between blood and dialysis solution. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. Thus optimized flow distribution both in the blood and dialysate compartment becomes quintessential for the maximal efficiency of the diffusion process within the hemodialyzer. The present paper describes the distribution of the blood and dialysate flows in a new low flux polysulfone hollow fiber hemodialyzer characterized by a specific undulation of the fibers and a new cutting technology of the fibers for an improved micro-flow condition in the blood compartment headers. Twelve Diacap alpha Polysulfone LO PS 15 (1.5 sqm) (B. Braun Medizintechnologie, Melsungen Germany) were employed for the study. Six were analyzed in vitro and six were studied in vivo. Blood flow distribution was studied in vitro by dye injection in the blood compartment during experimental extracorporeal circulation utilizing human blood with hematocrit adjusted at 33%. Sequential images were obtained with a helical scanner in a fixed longitudinal section of the dialyzer 1 cm thick. Average and regional blood flow velocities were measured utilizing the reconstructed imaging sequence. The method allowed the calculation of single fiber blood flow (SF Qb) and the mass transfer zone (MTR) definition in digitally subtracted images. The patterns 20-10 and 40-30 were utilized. The same technology was used to evaluate flow distribution in the dialysate compartment after dye injection in the Hansen's connector. Regional dialysate flow was calculated in central and peripheral sample areas of 1 cm2. Six in vivo hemodialysis treatments on patients with end stage renal disease were performed at three different blood flow rates (250-350 and 450 ml/min) in order to measure urea, creatinine and phosphate clearance. Macroscopic and densitometrical analysis revealed that flow distribution was homogeneous in the blood compartment while in the dialysate compartment a slight difference between the peripheral and central regions in terms of flow velocity was observed. This however was not generating channeling phenomena. Urea creatinine and phosphate clearances were remarkably high and so were the Kt/V observed in all sessions, especially in relation to the studied blood flows. In conclusion, a significant blood to dialysate flow match with optimized countercurrent flow condition was observed in the studied hollow fiber hemodialyzers. Such optimization might be due both to the improved dialyzer design at the level of the blood header and to the specific fiber undulation that prevents dialysate channeling.

Iron management in hemodialysis patients: optimizing outcomes in Vicenza, Italy.

The management of anemia in uremic patients undergoing hemodialysis requires the appropriate combination of erythropoietin treatment, iron supplementation, and on occasion androgen therapy. Identifying and correcting functional iron deficiency is crucial to optimizing erythropoietin efficiency. Recently, however, the trend to administer maintenance iron with resultant high serum ferritin and high transferrin saturation has led to an increase in reports of iron overload. Oral iron supplementation is inexpensive and safe, but poor patient compliance and reduced intestinal absorption may limit its efficacy. Intravenous iron, on the other hand, is effective, and its safety is related to the iron salt used. Currently available data suggest that iron saccharate may be the safest iron salt available for intravenous administration, although iron gluconate is safer than the dextran forms of intravenous iron. It should be kept in mind, however, that all forms of intravenous iron may have the potential of inducing iron overload. At this time, the levels of ferritin that define iron overload are not clearly established. The side effects of iron overload are well recognized (infections, malignancies, vascular diseases); however, no guidelines exist for safe practice. There are many markers of iron deficiency, with serum ferritin and hypochromic red cell percentage currently the best markers available in clinical practice.