The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock

John A Kellum, Lakhmir S Chawla, Christopher Keener, Kai Singbartl, Paul M Palevsky, Francis L Pike, Donald M Yealy, David T Huang, Derek C Angus, ProCESS and ProGReSS-AKI Investigators, Derek C Angus, Lakhmir S Chawla, David T Huang, Christopher Keener, John A Kellum, Nicole Lucko, Paul M Palevsky, Francis Pike, Kai Singbartl, Ali Smith, Donald M Yealy, Sachin Yende, Derek C Angus, Amber E Barnato, Tammy L Eaton, Elizabeth Gimbel, David T Huang, Christopher Keener, John A Kellum, Kyle Landis, Francis Pike, Diana K Stapleton, Lisa A Weissfeld, Michael Willochell, Kourtney A Wofford, Donald M Yealy, Erik Kulstad, Hannah Watts, Arvind Venkat, Peter C Hou, Anthony Massaro, Siddharth Parmar, Alexander T Limkakeng Jr, Kori Brewer, Theodore R Delbridge, Allison Mainhart, Lakhmir S Chawla, James R Miner, Todd L Allen, Colin K Grissom, Stuart Swadron, Steven A Conrad, Richard Carlson, Frank LoVecchio, Ednan K Bajwa, Michael R Filbin, Blair A Parry, Timothy J Ellender, Andrew E Sama, Jonathan Fine, Soheil Nafeei, Thomas Terndrup, Margaret Wojnar, Ronald G Pearl, Scott T Wilber, Richard Sinert, David J Orban, Jason W Wilson, Jacob W Ufberg, Timothy Albertson, Edward A Panacek, Sohan Parekh, Scott R Gunn, Jon S Rittenberger, Richard J Wadas, Andrew R Edwards, Matthew Kelly, Henry E Wang, Talmage M Holmes, Michael T McCurdy, Craig Weinert, Estelle S Harris, Wesley H Self, Diane Dubinski, Carolyn A Phillips, Ronald M Migues, John A Kellum, Lakhmir S Chawla, Christopher Keener, Kai Singbartl, Paul M Palevsky, Francis L Pike, Donald M Yealy, David T Huang, Derek C Angus, ProCESS and ProGReSS-AKI Investigators, Derek C Angus, Lakhmir S Chawla, David T Huang, Christopher Keener, John A Kellum, Nicole Lucko, Paul M Palevsky, Francis Pike, Kai Singbartl, Ali Smith, Donald M Yealy, Sachin Yende, Derek C Angus, Amber E Barnato, Tammy L Eaton, Elizabeth Gimbel, David T Huang, Christopher Keener, John A Kellum, Kyle Landis, Francis Pike, Diana K Stapleton, Lisa A Weissfeld, Michael Willochell, Kourtney A Wofford, Donald M Yealy, Erik Kulstad, Hannah Watts, Arvind Venkat, Peter C Hou, Anthony Massaro, Siddharth Parmar, Alexander T Limkakeng Jr, Kori Brewer, Theodore R Delbridge, Allison Mainhart, Lakhmir S Chawla, James R Miner, Todd L Allen, Colin K Grissom, Stuart Swadron, Steven A Conrad, Richard Carlson, Frank LoVecchio, Ednan K Bajwa, Michael R Filbin, Blair A Parry, Timothy J Ellender, Andrew E Sama, Jonathan Fine, Soheil Nafeei, Thomas Terndrup, Margaret Wojnar, Ronald G Pearl, Scott T Wilber, Richard Sinert, David J Orban, Jason W Wilson, Jacob W Ufberg, Timothy Albertson, Edward A Panacek, Sohan Parekh, Scott R Gunn, Jon S Rittenberger, Richard J Wadas, Andrew R Edwards, Matthew Kelly, Henry E Wang, Talmage M Holmes, Michael T McCurdy, Craig Weinert, Estelle S Harris, Wesley H Self, Diane Dubinski, Carolyn A Phillips, Ronald M Migues

Abstract

Rationale: Septic shock is a common cause of acute kidney injury (AKI), and fluid resuscitation is a major part of therapy.

Objectives: To determine if structured resuscitation designed to alter fluid, blood, and vasopressor use affects the development or severity of AKI or outcomes.

Methods: Ancillary study to the ProCESS (Protocolized Care for Early Septic Shock) trial of alternative resuscitation strategies (two protocols vs. usual care) for septic shock.

Measurements and main results: We studied 1,243 patients and classified AKI using serum creatinine and urine output. We determined recovery status at hospital discharge, examined rates of renal replacement therapy and fluid overload, and measured biomarkers of kidney damage. Among patients without evidence of AKI at enrollment, 37.6% of protocolized care and 38.1% of usual care patients developed kidney injury (P = 0.90). AKI duration (P = 0.59) and rates of renal replacement therapy did not differ between study arms (6.9% for protocolized care and 4.3% for usual care; P = 0.08). Fluid overload occurred in 8.3% of protocolized care and 6.3% of usual care patients (P = 0.26). Among patients with severe AKI, complete and partial recovery was 50.7 and 13.2% for protocolized patients and 49.1 and 13.4% for usual care patients (P = 0.93). Sixty-day hospital mortality was 6.2% for patients without AKI, 16.8% for those with stage 1, and 27.7% for stages 2 to 3.

Conclusions: In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care.

Keywords: acute kidney injury; early goal-directed therapy; resuscitation; sepsis; septic shock.

Figures

Figure 1.
Figure 1.
Study cohort. The top panel displays the analysis cohort by treatment arm. The bottom panel shows acute kidney injury (AKI) status at enrollment and subsequently, as well as AKI stages. Crt = creatinine; EGDT = early goal-directed therapy; PSC = protocol-based standard care.
Figure 2.
Figure 2.
Cumulative fluid use by study arm. Total fluid received over the first 6 hours. Solid line, usual care; long dashes, early goal-directed therapy; short dashes, protocol-based standard care.
Figure 3.
Figure 3.
Survival by acute kidney injury (AKI) and recovery status. (Top panel) One-year survival by AKI status (no AKI, stage 1, 2, or 3). (Bottom panel) One-year survival for stage 2 to 3 AKI by recovery status (complete, partial, none).

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