Critical Care 2009, 13:1014

Despite 21st century definitions, the management of acute kidney injury remains steadfastly rooted in the 20th century with treatment being principally supportive. Protection from potential causative agents is an essential part of management and to that end protection against contrast-induced nephropathy has received yet more attention. When optimization of volume status, haemodynamic parameters, electrolyte and acid-base disturbances have failed we turn to renal replacement therapy. The time ‘bought’ on renal support gives a period for renal recovery but although renal replacement therapy is widely employed, many management issues remain unanswered, including the timing, duration and the dose of treatment. In contrast to respiratory support for acute lung injury, for example, there is a paucity of large randomized studies addressing these fundamental issues. We describe some recent studies focusing on these issues with the hope that they may lead to better treatment for our patients.

NEJM 2009;361:1627-1638

The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury.

Methods
We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization.

Results
Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P<0.001).

Conclusions
In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days.

Critical Care 2008;12:R163

Drotrecogin alfa (activated) (DrotAA) is licensed for the treatment of severe sepsis with multiple organ failure. Patients with severe sepsis on renal replacement therapy (RRT), who typically receive additional anticoagulation to prevent circuit clotting, may be at higher risk of bleeding when DrotAA is administered in addition to standard anticoagulation. However, the effects of DrotAA on filter duration in the absence of additional anticoagulation are not established. The aim of this study was to analyse the filter survival time (FST), and to quantify the requirement of packed red cells (PRC) and blood products during DrotAA infusion.

Methods
This was a single-centre, retrospective observational study conducted in an adult intensive care unit (ICU). Thirty-five patients with severe sepsis who had received both RRT and DrotAA were identified, and all relevant clinical and laboratory data were retrieved from the departmental electronic patient record. We compared haemofilter parameters, blood products requirement and haemodynamic data recorded during RRT and the infusion of DrotAA with those recorded on RRT with standard anticoagulation after the DrotAA infusion had been completed (post-DrotAA).

Results
The proportion of filter changes due to filter clotting was similar during DrotAA infusion and with conventional anticoagulation post-DrotAA infusion. There was no difference in the FST and filter parameters during DrotAA in the presence or absence of additional anticoagulation with heparin or epoprostenol. A similar proportion of patients required red cell transfusion, although a greater proportion of patients received platelet and fresh frozen plasma (FFP) during DrotAA infusion compared to the post-DrotAA period with no difference between medical and surgical patients.

Conclusions
Additional anticoagulation during DrotAA infusion does not appear to improve FST. The use of DrotAA in patients with severe sepsis requiring RRT is safe and is not associated with an increased need for PRC transfusion or major bleeding events.

Critical Care 2008, 12:230

We summarize original research in the field of critical care nephrology that was accepted for publication or published in 2007 in Critical Care and, when considered relevant or directly linked to this research, in other journals. Four main topics were identified for a brief overview. The first of these was the definition of acute kidney injury and recent evidence showing the validity of RIFLE (Risk, Injury, Failure, Loss and End-stage kidney disease) criteria and the recent Acute Kidney Injury Network review of the same criteria. Second, we cover the clinical and experimental utilization of novel biomarkers for diagnosis of acute kidney injury, giving special attention to neutrophil gelatinase-associated lipocalin protein. The third area selected for review is outcomes of acute kidney injury during the past 10 years, described by a recent Austrailian epidemiological study. Finally, specific technical features of renal replacement therapies were examined in 2007, specifically regarding anticoagulation and vascular access.

NEJM 2008;359:7-20

The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial.

Methods
We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour.

Results
Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P=0.47). There was no significant difference between the two groups in the duration of renal-replacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups.

Conclusions
Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour.

Contin Educ Anaesth Crit Care Pain 2006 6: 197-202

• Continuous renal replacement therapy (CRRT) techniques are the method of choice for renal replacement in UK Intensive care units.
• CRRT ensures solute and volume removal in haemodynamically stable conditions.
• The inherent stability of CRRT may avoid the renal ischaemia caused by hypotension associated with intermittent haemodialysis (IHD).
• The major risk of CRRT is bleeding secondary to circuit anticoagulation.
• High volume haemofiltration (HVHF) may have a role in the management of sepsis via removal of ‘middle molecules’.