In counterpart, although a MAP of at least 65 mmHg is thought to be protective against organ failures, including renal impairment, and is universally recommended [8], the true value of MAP that could really protect renal function against www.selleckchem.com/products/Erlotinib-Hydrochloride.html worsening is still unknown. In human septic shock, two interventional prospective studies of limited size [9,10] have shown that increasing MAP from 65 to 75 or 85 mmHg with norepinephrine did not result in urinary output nor serum creatinine significant improvement. Conversely, in another recent study [11], increasing MAP from 65 to 75 mmHg resulted in an increase in urinary output in 11 septic shock patients. Further, a recent retrospective cohort study suggested that levels of MAP higher than 75 mmHg could be necessary to insure renal protection during sepsis and septic shock [12].

In healthy conditions RBF is stable within a wide range of MAP, due to regional autoregulation [13]. However, in shock states, and particularly in septic shock, derangements in microcirculation and vasoreactivity, although not precisely examined for human renal perfusion, tend to increase the lowest MAP threshold that guarantees autoregulation [14]. In addition, animal studies have shown that in ischemic AKI, a decrease in MAP even at high levels of MAP (above 90 mmHg) could be responsible of a decrease in RBF, suggesting an impairment of autoregulation in AKI [15-18]. This suggests that independently of the shock state itself, shock-induced AKI could cause the partial or total loss of the renal autoregulation ability early in the course of the disease [17].

This could explain the discrepancies between the above-cited human studies [9-12] concerning the relation between MAP and renal function as they included patients regardless of the existence or not of AKI at the time of inclusion. However, at this time, human studies addressing the link between shock-induced AKI and the loss of autoregulation are lacking.We hypothesized that, due to different MAP thresholds of renal autoregulation, patients with or without AKI at the time of initial therapy for acute circulatory failure could need different MAP levels to prevent the worsening of renal function or even to favour its improvement.Accordingly, we conducted an explorative, prospective study aimed at comparing the relation between MAP and renal function in patients admitted for GSK-3 acute circulatory failure with different degrees of initial renal function impairment.Materials and methodsThe protocol met the criteria of a noninterventional study design as defined by the French Law [19]. The Ethics Committee of the Association des R��animateurs du Centre-Ouest, France approved the protocol and waived informed consent.