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Abstract
Evidence is accumulating showing that septic acute kidney injury (AKI) is different from non-septic AKI. Specifically, a large body of research points to apoptotic processes underlying septic AKI. Unravelling the complex and intertwined apoptotic and immuno-inflammatory pathways at the cellular level will undoubtedly create new and exciting perspectives for the future development (e.g., caspase inhibition) or refinement (specific vasopressor use) of therapeutic strategies. Shock complicating sepsis may cause more AKI but also will render treatment of this condition in an hemodynamically unstable patient more difficult. Expert opinion, along with the aggregated results of two recent large randomized trials, favors continuous renal replacement therapy (CRRT) as preferential treatment for septic AKI (hemodynamically unstable). It is suggested that this approach might decrease the need for subsequent chronic dialysis. Large-scale introduction of citrate as an anticoagulant most likely will change CRRT management in intensive care units (ICU), because it not only significantly increases filter lifespan but also better preserves filter porosity. A possible role of citrate in reducing mortality and morbidity, mainly in surgical ICU patients, remains to be proven. Also, citrate administration in the predilution mode appears to be safe and exempt of relevant side effects, yet still requires rigorous monitoring. Current consensus exists about using a CRRT dose of 25 ml/kg/h in non-septic AKI. However, because patients should not be undertreated, this implies that doses as high as 30 to 35 ml/kg/h must be prescribed to account for eventual treatment interruptions. Awaiting results from large, ongoing trials, 35 ml/kg/h should remain the standard dose in septic AKI, particularly when shock is present. To date, exact timing of CRRT is not well defined. A widely accepted composite definition of timing is needed before an appropriate study challenging this major issue can be launched.
Highlights
Continuous renal replacement therapy (CRRT) and especially continuous veno-venous hemofiltration (CVVH) are widely used in intensive care units (ICU)
This review was designed to address the most recent knowledge and future developments with regard to continuous and intermittent renal replacement therapy (IRRT) that are of practical interest to ICU physicians
In view of the high mortality rate in septic shock, a higher dose is required as salvage therapy in this condition
Summary
Continuous renal replacement therapy (CRRT) and especially continuous veno-venous hemofiltration (CVVH) are widely used in intensive care units (ICU). The authors concluded that apoptotic kidney cells may act as a source of local inflammation producing subsequent non-apoptotic renal injury [83] Another recent study [84] showed that plasma from septic burn patients with AKI could initiate pro-apoptotic effects and in vitro functional alterations of renal tubular cells and podocytes that correlated with the degree of proteinuria and renal dysfunction. A recent study showed that extracorporeal therapy with polymyxin B therapy reduced the pro-apoptotic activity of plasma of septic patients on cultured renal cells, providing further evidence for a preponderant role of apoptosis in the development of sepsis-related AKI [86]. During well-resuscitated septic shock after porcine peritonitis, low-dose arginine vasopressin is associated with less kidney damage by reducing both tubular apoptosis and systemic inflammation compared with noradrenaline [102]
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