A Unified Theory of Sepsis-Induced Acute Kidney Injury

Abstract

Given that the leading clinical conditions associated with Acute kidney injury (AKI), namely, sepsis, major surgery, heart failure and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macro-hemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a “unifying theory” to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria and that it ultimately results in and explains the clinical phenotype of sepsis induced AKI.

Ventilator-induced lung injury increases expression of endothelial inflammatory mediators in the kidney

“…Incidence of AKI rises with the increasing severity of sepsis (2,30), and sepsis accounts for nearly 50% of episodes of AKI in critically ill patients (35). Moreover, sepsis and VILI often occur simultaneously, as sepsis is the leading cause of both ARDS and MOF (13,15). These challenges are barriers to understanding better the pathophysiology of AKI due to VILI and to the development of novel strategies aimed at mitigating AKI due to VILI in critical illness.…”

The Central Role of Renal Microcirculatory Dysfunction in the Pathogenesis of Acute Kidney Injury

“…In a unified approach, Gomez et al [33] identified mitochondrial dysfunction as a key contributor to the development of AKI. Mitochondrial function is critical not only for the production of ATP needed for sodium reabsorption but also because of its role as a prime generator of oxygen radicals during oxidative phosphorylation.…”

An observational study on the relationship between plasma vitamin C, blood glucose, oxidative stress, endothelial dysfunction and outcome in patients with septic shock

“…[27] Endothelial dysfunction in sepsis has been demonstrated to cause microvascular dysfunction, the motor for sepsis-induced organ dysfunction and failure that may be reflected by SOFA score. [28][29][30] The baseline oxidative stress marker in this study was significantly higher in the non-survivors, who also had increased organ dysfunction when compared with survivors. These results, therefore, demonstrate that increased oxidative stress is a marker of increased risk of death; this finding supports previous similar findings of other researchers.…”