Early and appropriate goal-directed fluid therapy is fundamental in acute resuscitation of these kinase inhibitor Rucaparib critically ill patients; however, it is almost always associated with a certain degree of fluid overload, especially in septic patients, which promotes tissue edema that could potentially contribute, itself, to progressive organ dysfunction. Both fluid balance and urine volume are independent predictors of mortality in adult critically ill patients with AKI [31].Plachouras et al. [12] studied the pharmacokinetics of intravenously administered CMS in critically ill patients and concluded that a loading dose of at least 9 million IU of CMS is needed in these cases to produce plasma concentrations of the drug within the minimum inhibitory concentration (MIC) range indicative of susceptibility.

Failure to achieve such concentrations can lead to the emergence of resistant strains, and it can also result in increased mortality.In light of these findings, we decided to investigate the nephrotoxicity of high-dose CMS therapy, in terms of RIFLE-defined AKI, in patients with no AKI at baseline. Hartzell and collaborators [25] used a similar approach in a young and otherwise healthy population of patients on a general medicine ward. The patients had no other confounding comorbidity, but the mean duration of CMS therapy was longer than it was in our study. The authors found a significant association between the cumulative CMS dose and the risk of nephrotoxicity in patients receiving CMS for more than 14 days.

This finding contrasts with the results of our logistic regression analysis, which showed that neither the cumulative CMS dose nor the duration of treatment was a risk factor for developing new-onset AKI in severely ill ICU patients. The median days of CMS treatment of our patients, however, was lower that than reported by Hartzell and collaborators and could probably justify the discordance with our results as well as the difference in severity of the two population studied. Carfilzomib We agree, nevertheless, that creatinine levels need to be closely monitored in patients receiving prolonged treatment with CMS.Pogue et al. [26] reported that CMS nephrotoxicity is related to the daily dose but not to cumulative exposure. However, the population they studied was heterogeneous in terms of pre-treatment renal function. Furthermore, although illness severity scores were not reported, their patients were probably not as critically ill as ours. Only 14% had septic shock, 15% were on vasopressors and only 62% were being mechanically ventilated.