Kellum and Lameire [
1] proposed the concept of risk factors and susceptibility. The main external stressors that may cause AKI include sepsis, shock, burns, trauma, cardiopulmonary bypass, nephrotoxic drugs, radiocontrast agents, and poisonous plants and animals. However, the chances of developing AKI after exposure to the same insult depend on a number of `susceptibility factors’ that vary widely from individual to individual. For susceptibility factors we may consider advanced age, dehydration or volume depletion, female gender, black race, chronic kidney disease, diabetes mellitus, cancer and anemia. Therefore, it is important to screen patients who have undergone an exposure and to continue monitoring them until the risk has subsided. To better interpret the pathophysiology of AKI and its interplay with several hemodynamic variables, a retrospective study including 137 septic ICU patients was performed [
18]: AKI was defined as occurrence of a novel AKI case or an increase in the stage of previously diagnosed AKI during the first 5 days following ICU admission based on the AKIN criteria. Central venous pressure (CVP), cardiac output, mean arterial pressure (MAP), diastolic arterial pressure (DAP), central venous oxygen saturation (ScvO
2) or mixed venous oxygen saturation were analyzed. One-half of patients in the study had new or persistent AKI. MAP, ScvO
2 and cardiac output were not significantly different between AKI and non-AKI patients. The development or progression of AKI, regardless of the level of fluid balance and positive end-expiratory pressure, was strongly associated with the CVP level. This suggests participation of venous congestion in the physiopathology of AKI in severe sepsis and septic shock. Patients with AKI had lower DAP and higher CVP (
P = 0.0003). Although the role of renal hypoperfusion (low cardiac output or hypovolemia) is believed to contribute to the development of sepsis-induced renal dysfunction, AKI appears to be only partially reversible after the optimization of systemic hemodynamics [
18]. Fluid resuscitation and pressure optimization is a landmark treatment for septic patients in order to improve renal perfusion pressure. For some patients, the induced CVP elevation may overcome the DAP increase, reducing renal perfusion with harmful effects on renal function. This aspect is supported by the recently reported association between fluid overload and mortality in critically ill patients, especially in patients with AKI or septic shock [
19]. The creation of a vicious circle with oliguria and fluid-loading may then aggravate AKI. Therefore, targeting a pre-defined CVP as a therapeutic target might not be suitable in septic patients. Legrand and colleagues suggested instead that hemodynamic targets are best achieved at low CVPs (that is, a CVP less than 8 to 12 mmHg) [
18]. The Surviving Sepsis Campaign guidelines [
20] mention that `in mechanically ventilated patients or those with known preexisting decreased ventricular compliance, a higher target CVP of 12-15 mmHg should be achieved to account for the impediment in filling’. The results of this study suggest, instead, that such targets might be too high from a `renal’ perspective. Therefore, a strategy of fluid restriction in these patients is an important option to be considered.
Poukkanen and coworkers [
21] evaluated if a higher MAP maintained during the first 24 hours of ICU admission is associated with a lower risk of progression of AKI in patients with severe sepsis. More than 400 patients with severe sepsis were enrolled in this prospective observational study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the KDIGO criteria. AKI progressed in 153 patients (36.2%) and these patients had significantly lower time-adjusted MAP (74.4 mmHg (68.3 to 80.8)), than those without progression (78.6 mmHg (72.9 to 85.4)) (
P <0.001). A cutoff value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. These authors also found that chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI. Interestingly, a more recent randomized controlled trial assigning septic shock patients to arms with MAP targets of 80 to 85 mmHg (high-target group) or 65 to 70 mmHg (low-target group) found renal outcome differences only in patients with chronic hypertension [
22]. The main difference between the observational study of Poukkanen and colleagues and the prospective SEPSISPAM study is that, in the first, hypotensive patients were those with the highest vasopressor loads and, in the second, the high target group received the largest amount of vasoactive drugs. It can only be concluded that, possibly, the underlying septic syndrome severity rather than MAP or inotropic score is the most important determinant of renal function.