August 31, 2020

An article review from the ESICM Journal Review Club

Mortality and host response aberrations associated with transient and persistent AKI in critically ill patients with sepsis: a prospective cohort study

Sepsis remains the main cause of acute kidney injury (AKI) in intensive care units (ICUs), accounting for 50% of all cases (Sepsis-associated AKI, S-AKI [1]).

Considering the singularity of S-AKI pathogenesis, Uhel et al conducted a prospective observational study to determine the incidence and mortality associated with transient and persistent AKI (using the ADQI – Acute Disease Quality Initiative Workgroup, definitions [1]) in septic patients.

Additionally, the authors analysed the plasma biomarkers and the whole-genome blood leukocyte transcriptomes implicated in the pathogenesis of the sepsis event, between patients without AKI, and those with transient or persistent AKI.

A total of 1,545 patients admitted with sepsis to two Dutch ICUs were stratified according to the presence and evolution of AKI, defined by the RIFLE classification [2] within the first 48 hours (with persistent AKI defined as remaining > 48 h [1]).

The results showed AKI occurred in 37.7% of patients, of which 18.4% was transient and 81.6% persistent.

On admission, patients with persistent AKI had higher disease severity scores and more frequently severe RIFLE AKI stages (injury or failure) than transient AKI patients.

In a logistic regression analysis, persistent AKI – but not transient AKI – independently impacted patient outcome, with more than twofold increased odds for 30-day mortality, when compared with no AKI.

16 plasma biomarkers involved in sepsis pathogenesis were analysed.

Persistent AKI was associated with more prominent signs of endothelial cell activation, more severe loss of vascular integrity, and stronger activation of the coagulation system (prolonged prothrombin time and activated partial thromboplastin time, elevated plasma levels of D-dimer, and reduced platelet counts and levels of natural anticoagulants antithrombin and protein C) during the first 4 days, compared to transient AKI.

Baseline blood gene expression showed minimal differences with respect to the presence or evolution of AKI.

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[1] Chawla, L. S. et al. Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initia-tive (ADQI) 16 Workgroup. Nat. Rev. Nephrol. 13, 241–257 (2017).
[2] Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L. & Palevsky, P. Acute renal failure–definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit. Care 8, R204 (2004).

 

STUDY STRENGTHS & LIMITATIONS

– A large cohort of sepsis patients.
– This is the first evaluation of the recent ADQI consensus definitions for transient and persistent AKI in sepsis patients.
– Daily RIFLE scores were collected prospectively.
– Conclusions based on strong subgroup and sensitivity analyses.
– Data were collected several years ago (2011–2013), but guidelines for the management of AKI and use of renal replacement therapy have not changed since then.

TAKE HOME MESSAGE

– Besides the severity of AKI, the duration of renal dysfunction independently affects short- and long-term mortality during sepsis.
– Persistent but not transient AKI is independently associated with sepsis mortality.
– Compared to transient AKI, persistent AKI is associated with sustained systemic inflammation, coagulation activation and loss of vascular integrity.

 

This article review was prepared and submitted by Dr Serena Ranieri, Department of Anaesthesia, Intensive Care and Emergency Medical Services, Maggiore Hospital, Bologna, Italy, on behalf of the ESICM Journal Review Club.


REFERENCES
  1. Chawla, L. S. et al. Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat. Rev. Nephrol. 13, 241–257 (2017)
  2. Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L. & Palevsky, P. Acute renal failure–definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit. Care 8, R204 (2004)

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