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Cited by 40Acute Kidney Injury ResearchChronic Kidney Disease and DiabetesSepsis Diagnosis and Treatment

Acute Kidney Injury and Adverse Outcomes of Critical Illness: Correlation or Causation?

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Girling, Benedict J, Channon, Samuel W, Haines, Ryan W, Prowle, John R·2020·Clinical Kidney Journal
DOI 10.1093/ckj/sfz158PMC PMC7147312
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Abstract

Critically ill patients who develop acute kidney injury (AKI) are more than twice as likely to die in hospital. However, it is not clear to what extent AKI is the cause of excess mortality, or merely a correlate of illness severity. The Bradford Hill criteria for causality (plausibility, temporality, magnitude, specificity, analogy, experiment & coherence, biological gradient and consistency) were applied to assess the extent to which AKI may be causative in adverse short-term outcomes of critical illness. Plausible mechanisms exist to explain increased risk of death after AKI, both from direct pathophysiological effects of renal dysfunction and mechanisms of organ cross-talk in multiple-organ failure. The temporal relationship between increased mortality following AKI is consistent with its pathophysiology. AKI is associated with substantially increased mortality, an association that persists after accounting for known confounders. A biological gradient exists between increasing severity of AKI and increasing short-term mortality. This graded association shares similar features to the increased mortality observed in ARDS; an analogous condition with a multifactorial aetiology. Evidence for the outcomes of AKI from retrospective cohort studies and experimental animal models is coherent however both of these forms of evidence have intrinsic biases and shortcomings. The relationship between AKI and risk of death is maintained across a range of patient ages, comorbidities and underlying diagnoses. In conclusion many features of the relationship between AKI and short-term mortality suggest causality. Prevention and mitigation of AKI and its complications are valid targets for studies seeking to improve short-term survival in critical care.

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Authors
Girling, B. J., Channon, S. W., Haines, R. W., & Prowle, J. R.
Affiliations
  • Queen Mary University of London (GB)
  • Critical Care and Perioperative Medicine Research Group, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK
Corresponding author
Girling, Benedict J
ORCID
Venue
Clinical Kidney Journal
Publisher
Oxford University Press (OUP)
Published
2019-11-18
Volume
13
Issue
2
Pages
133-141
ISSN
  • 2048-8505 (ISSN-L)
  • 2048-8513
DOI
10.1093/ckj/sfz158
PMC
PMC7147312
OpenAlex
W2987857474
Cited by
40
References
1
Citations by year
2026: 5 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 13 · 2019: 1
FWCI
0.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Kidney Journal (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by-nc)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
Keywords
acute kidney injury, critical illness, mortality, Bradford Hill criteria, causality, multiple organ failure, organ crosstalk, acute respiratory distress syndrome, biological gradient, short-term survival, renal dysfunction

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