Septic acute kidney injury: new concepts

Area of Science:

• Nephrology
• Critical Care Medicine
• Pathophysiology

Background:

• Acute kidney injury (AKI) is a frequent and serious complication in intensive care unit (ICU) patients, often linked to severe sepsis and septic shock.
• High mortality rates persist in septic critically ill patients with AKI, underscoring gaps in understanding sepsis-induced renal dysfunction.
• Existing paradigms consider septic AKI primarily a result of kidney ischemia.

Purpose of the Study:

• To challenge the established dogma that kidney ischemia is the primary cause of sepsis-induced AKI.
• To explore emerging concepts regarding the pathogenesis of septic AKI.
• To propose a new conceptual framework for investigating and intervening in septic AKI.

Main Methods:

• Review of recent experimental sepsis models simulating human hemodynamic conditions (e.g., hyperdynamic sepsis).
• Analysis of renal blood flow and vascular resistance in experimental sepsis.
• Preliminary studies in septic sheep measuring renal bioenergetics (ATP levels) using phosphorus coil and magnetic resonance technology.

Main Results:

• Experimental models demonstrate increased renal blood flow and decreased renal vascular resistance in hyperdynamic sepsis.
• These findings suggest that septic AKI can occur despite renal hyperemia, without necessitating ischemia.
• Preliminary data indicate preserved renal bioenergetics in advanced septic shock, challenging established views.

Conclusions:

• Septic AKI may not always be caused by kidney ischemia, contrary to traditional understanding.
• Renal hyperemia might coexist with the loss of glomerular filtration rate (GFR) in septic AKI.
• These novel insights necessitate a re-evaluation of septic AKI pathogenesis and potential therapeutic targets.