Study definitions.

Nephrotoxicity was defined as an increase of at least 1.5 times the baseline SCr value according to RIFLE criteria. The severity of nephrotoxicity was assessed at peak SCr (highest value compared to baseline) during PMB therapy. Nephrotoxicity was classified as risk, injury, or failure on the basis of SCr increases of 1.5, 2.0, and 3.0 times the baseline, respectively. Loss was defined as persistent acute renal failure or loss of function for >4 weeks. Patients requiring renal replacement therapy for >3 months were classified under end-stage renal disease. To qualify for the risk category, two consecutive SCr elevations of 1.5 times the baseline SCr were required. The time to nephrotoxicity was defined as the first date RIFLE criteria, regardless of the severity, were met. The diagnosis of severe sepsis and septic shock was made in accordance with the international guidelines for the management of severe sepsis and septic shock (25). Among patients who developed nephrotoxicity, the recovery from acute kidney injury (AKI) was defined by a return of SCr to levels below the original threshold for meeting AKI.