Septic AKI in ICU patients. diagnosis, pathophysiology, and treatment type, dosing, and timing: a comprehensive review of recent and future developments

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.

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

“…Approximately 80% of acute renal failure is caused by renal tubular injury (20,21). The pathophysiological process of AKI induced by sepsis is extremely complex and severely affects patient survival.…”

Early report: The use of Cytosorb™ haemabsorption column as an adjunct in managing severe sepsis: initial experiences, review and recommendations

“…23 There are a variety of extracorporeal therapies available which can remove components of the inflammatory response. However, there are at least theoretical reasons why Cytosorb may be different and could potentially offer unique therapeutic advantages warranting more rigorous evaluation.…”

Chloroquine prevents acute kidney injury induced by lipopolysaccharide in rats via inhibition of inflammatory factors

“…HMGB-1 binds to inflammatory mediators and induces the release of pro-inflammatory cytokines [17]. KIM-1, a transmembrane tubular protein, is expressed in the kidneys after renal injury and serves as a marker of renal injury [17]. Kidney injury involves an inflammatory reaction [18].…”

“…Pre-treatment of LPStreated animals with YOH blocked the effects of CQ, suggesting that CQ elicits its effects via the α-2 adrenoceptor. HMGB-1 binds to inflammatory mediators and induces the release of pro-inflammatory cytokines [17]. KIM-1, a transmembrane tubular protein, is expressed in the kidneys after renal injury and serves as a marker of renal injury [17].…”