Acute Kidney Injury and Kidney Replacement Therapy in the Critically Ill Patient
detecting AKI (Figure 2). When the KDIGO guidelines were released in 2012, these data were not
available; thus, they were not included in the criteria for the diagnosis of AKI. Despite emerging
literature and calls for revision of AKI classification to incorporate biomarkers, the most recent 2019
KDIGO controversies conference on AKI suggests that additional research is needed before including
these biomarkers in the diagnostic criteria for AKI.
Morbidity
Mortality
Early detection and
diagnostic biomarkers
(e.g. NGAL, KIM-1,
L-FABP, SCr, UOP, Cystatin C)
Warning biomarkers
(e.g. TIMP2*IGFBP7)
NKD
Increased
risk for AKI
Kidney
damage
Decreased
GFR
Kidney
failure
Functional markers: Indicate the kidneyβs capacity for clearance and are used to estimate GFR and
functional loss; these can help indicate a need for drug dosing changes
Examples: SCr, UOP, serum cystatin C, proenkephalin, beta-trace protein, Ξ²2 microglobulin
ii.
These biomarkers may rise with or without evidence of structural damage to the kidney (e.g.,
prerenal AKI, which could correspond to a reduced GFR that may not yet have resulted in
kidney damage).
iii.
Recent evidence suggests that cystatin C can predict the pharmacokinetics of medications
as well as, if not better than, SCr with certain renally eliminated medications. Drug-specific
dosing models need to be developed and tested.
| (a) | Antimicrobials have been the most commonly studied drug class investigating the |
|---|
association between cystatin C, corresponding eGFR, and predicted drug clearance. Specific
medications that have been evaluated using cystatin C prediction of pharmacokinetics
include vancomycin, aminoglycosides, Ξ²-lactams, tenofovir, digoxin, dabigatran, and
carboplatin.
Damage/injury markers: Signal injury to the kidney cells or at least cellular distress; these can help
identify patients who would benefit from limiting exposure to nephrotoxins
Warning biomarkers (e.g., cell-cycle arrest markers [TIMP-2β’IGFBP7])
| (a) | TIMP-2β’IGFBP7 is a U.S. Food and Drug Administrationβapproved urinary test; these |
|---|
biomarkers are released during a pause (an βarrestβ) in mitosis when the biomarker
indicates the cell may be injured and should not divide.
| (b) | In the PrevAKI (Intensive Care Med 2017;43:1551-61) and BigpAK (Ann Surg |
|---|
2018;267:1013-20) trials, surgical patients with a high risk of AKI on the basis of [TIMP-
2β’IGFBP7] greater than 0.3 who were randomized to an AKI prevention bundle had a
lower incidence of AKI than did individuals who received usual care. This is a significant
advancement because it suggests that even in high-risk patients, AKI can be prevented.