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Review
. 2018 Jan;38(1):3-11.
doi: 10.1016/j.semnephrol.2017.09.002.

Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine

Dennis G Moledina  1 , Chirag R Parikh  2
Affiliations
Review

Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine

Dennis G Moledina et al. Semin Nephrol. 2018 Jan.

Abstract

Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with adverse short- and long-term outcomes. AKI is diagnosed by serum creatinine (SCr)-based consensus definitions that capture an abrupt decrease in glomerular filtration rate associated with AKI. However, SCr-based AKI definitions lack sensitivity and specificity for diagnosing structural kidney injury. Moreover, AKI is a heterogeneous condition consisting of distinct phenotypes based on its etiology, prognosis, and molecular pathways, and that may potentially require different therapies. SCr-based AKI definitions provide no information on these AKI phenotypes. This review highlights traditional and novel tools that overcome the limitations of SCr-based AKI definitions to improve AKI phenotyping.

Keywords: AKI; IL-18; IL-6; KIM-1; L-FABP; NGAL; biomarkers; creatinine; cystatin C; furosemide; urinary casts; urine microscopy.

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Conflict of interest statement

Conflict of Interest

DGM: Nothing to disclose

CRP: Nothing to disclose

Figures

Figure 1
Figure 1. Limitations of SCr-based AKI definition
SCr-based AKI definition may fail to identify individuals with structural kidney injury (“subclinical AKI”) or it incorrectly identifies individuals without structural kidney injury (“Hemodynamic AKI”). Even in individuals with structural kidney injury correctly identified by SCr-based AKI definition, it provides no information on AKI etiology, molecular pathways, therapy, or prognosis. ATI, acute tubular injury; AKI, acute kidney injury; SCr, serum creatinine; RAAS, renin angiotensin aldosterone system
Figure 2
Figure 2. Classification of biomarkers of AKI
SCr, serum creatinine; FENa, fractional excretion of sodium; KIM-1, kidney injury molecule-1; NGAL, neutrophil gelatinase-associated lipocalin; TIMP2, tissue inhibitor of metalloproteinases-2; IGFBP-7, insulin like growth factor binding protein-7; IL, interleukin; MCP-1, monocyte chemotactic protein 1
Figure 3
Figure 3. Subclinical ATI. In deceased donors without SCr-based AKI, NGAL levels were higher with increasing severity of ATI
NGAL, neutrophil gelatinase-associated lipocalin; ATI, acute tubular injury
Figure 4
Figure 4. Observed relative risk approaches null due to accidental enrolment of PRA patients in a trial of drug with true relative risk of 0.7 in ATI patients
Assuming 20% event rate in control and 5% event rate in PRA. Adapted from Parikh et. al. Kidney Int 2016. ATI, acute tubular injury; PRA, pre-renal azotemia
See this image and copyright information in PMC

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