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Journal Scan

September 2018

Towards a fuller understanding of acute kidney injury (AKI)

Summarized from Kellum J, Prowle J. Paradigms of acute kidney injury in the intensive care setting. Nature Reviews Nephrology 2018; 14: 217-30.
Thanks to KDIGO collaborative guidelines, diagnosis of acute kidney injury (AKI), defined as sudden decrease in kidney function (i.e. sudden decrease in glomerular filtration rate GFR), is simple and straight forwardly based on measurement of serum creatinine concentration and urine output. AKI is confirmed if any of the following criteria are satisfied:

rise in serum creatinine of 0.3 mg/dL (26.5 µmol/L) or more within 48 hours
a 50 % or greater rise in serum creatinine within past 7 days
reduction in urine output to less than 0.5 mL/kg/hr for 6 hours. 

If AKI diagnosis is simple, understanding the significance of that diagnosis is considerably more complex. These complexities are addressed in this highly authoritative review written by two intensive care physicians with internationally renowned research interest in intensive care nephrology. One of the authors, Dr John Kellum, is co-chair of the KDIGO committee responsible for the internationally recognized diagnostic definition of AKI outlined above. 

The complexity of AKI derives principally from the fundamental fact that it is not a single disease but a clinical syndrome that complicates the course of many diseases; understanding AKI requires that the context in which it occurs must be taken into account. The heterogeneity of AKI, with its ”multiple aetiologies, variable pathogenesis and diverse outcomes” is the starting point of this article. 

With their particular background in intensive care medicine, the authors choose to focus discussion on the subtypes of AKI that occur in four clinical situations commonly seen in the intensive care unit: sepsis; major surgery; renal hypoperfusion (reduced cardiac output); and exposure to nephrotoxins.

Under each of these four main headings the authors discuss current understanding of: the epidemiology of the associated AKI; the pathophysiology of the associated AKI; and the outcome of the associated AKI. 

They go on to discuss the similarities and differences in AKI pathophysiology that occur in these four etiological clinical contexts, revealing that even within these four contexts there is not a pathophysiological ”pure” subtype of AKI that can currently be identified. 

The final section of the article is devoted to discussion of research aimed at defining AKI subtypes by examining patterns of gene expression during specific animal models of kidney injury. This approach has allowed discovery of potentially useful biomarkers for AKI subtype definition. 

This is a wide-ranging and detailed review of what is currently understood about the heterogeneity of AKI in terms of epidemiology, pathophysiology and outcome. 
Understanding of the pathophysiological mechanisms discussed in the article is aided by three necessarily complex, but excellently designed graphics. 

May contain information that is not supported by performance and intended use claims of Radiometer's products. See also Legal info.

Chris Higgins

has a master's degree in medical biochemistry and he has twenty years experience of work in clinical laboratories.

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