Early reversible acute kidney injury is associated with improved survival in septic shock ☆ , ☆☆ Manish M. Sood, MD a , Leigh Anne Shafer, MD b , Julie Ho, MD b , Martina Reslerova, MD b , Greg Martinka, MD c , Sean Keenan, MD d , Sandra Dial, MD e , Gordon Wood, MD f , Claudio Rigatto, MD b , Anand Kumar, MD g, ⁎, and the Cooperative Antimicrobial Therapy in Septic Shock (CATSS) Database Research Group a Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada b Section of Nephrology, University of Manitoba, Manitoba, Canada c Richmond General Hospital, Vancouver, British Columbia, Canada d Royal Columbian Hospital, Vancouver, British Columbia, Canada e McGill University, Montreal Quebec, Canada f Royal Jubilee Hospital/Victoria General Hospital, Victoria British Columbia, Canada g Section of Critical Care Medicine, University of Manitoba, Manitoba, Canada abstract article info Keywords: Severe sepsis Acute tubular necrosis Outcome Acute renal failure Introduction: The fact that acute kidney injury (AKI) is associated with worse clinical outcomes forms the basis of most AKI prognostic scoring systems. However, early reversibility of renal dysfunction in acute illness is not considered in such systems. We sought to determine whether early (≤24 hours after shock documentation) reversibility of AKI was independently associated with in-hospital mortality in septic shock. Methods: Patient information was derived from an international database of septic shock cases from 28 different institutions in Canada, the United States and Saudi Arabia. Data from a final cohort of 5443 patients admitted with septic shock between Jan 1996 and Dec 2009 was analyzed. The following 4 definitions were used in regards to AKI status: (1) reversible AKI = AKI of any RIFLE severity prevalent at shock diagnosis or incident at 6 hours post- diagnosis that reverses by 24 hours, (2) persistent AKI = AKI prevalent at shock diagnosis and persisting during the entire 24 hours post-shock diagnosis, (3) new AKI = AKI incident between 6 and 24 hours post-shock diagnosis, and (4) improved AKI = AKI prevalent at shock diagnosis or incident at 6 hours post followed by improvement of AKI severity across at least one RIFLE category over the first 24 hours. Cox proportional hazards were used to determine the association between AKI status and in-hospital mortality. Results: During the first 24 hours, reversible AKI occurred in 13.0%, persistent AKI in 54.9%, new AKI in 11.7%, and no AKI in 22.4%. In adjusted analyses, reversible AKI was associated with improved survival (HR, 0.64; 95% CI, 0.53-0.77) compared to no AKI (referent), persistent AKI (HR, 0.99; 95% CI, 0.88-1.11), and new AKI (HR, 1.41; 95% CI, 1.22-1.62). Improved AKI occurred in 19.1% with improvement across any RIFLE category associated with a significant decrease in mortality (HR, 0.53; 95% CI, 0.45-0.63). More rapid antimicrobial administration, lower Acute Physiology and Chronic Health Evaluation II score, lower age, and a smaller number of failed organs (excluding renal) on the day of shock as well as community-acquired infection were independently associated with reversible AKI. Conclusion: In septic shock, reversible AKI within the first 24 hours of admission confers a survival benefit compared to no, new, or persistent AKI. Prognostic AKI classification schemes should consider integration of early AKI reversibility into the scoring system. © 2014 Elsevier Inc. All rights reserved. 1. Introduction Acute kidney injury (AKI) is associated with adverse outcomes, universally increasing mortality, length of hospital stay and the risk of long term chronic kidney disease and kidney failure [1–10]. In septic shock, AKI is especially common with the risk of worse outcomes increasing with the severity of injury [2,4,11–16]. Current classification schemes for defining AKI, such as the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease Journal of Critical Care xxx (2014) xxx–xxx ☆ All authors approved of this manuscript. ☆☆ Conflict of Interest Statement: Anand Kumar received unrestricted grant funding from Pfizer, Lilly, Astellas, Bayer, and Merck for the initial development of the CATSS Database. Additional grant funding has been provided by the Manitoba Research Council, the Health Sciences Foundation and the Deacon Foundation. No other author has significant conflict of interest. This specific analysis has not been supported. Manish Sood has salary support through the Jindal Research Chair for the Prevention of Kidney Disease at the University of Ottawa. ⁎ Corresponding author. Health Sciences Centre, JJ399, 700 William Ave, Winnipeg MB, R3A-1R9. http://dx.doi.org/10.1016/j.jcrc.2014.04.003 0883-9441/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Journal of Critical Care journal homepage: www.jccjournal.org Please cite this article as: Sood MM, et al, Early reversible acute kidney injury is associated with improved survival in septic shock, J Crit Care (2014), http://dx.doi.org/10.1016/j.jcrc.2014.04.003