False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria

Abstract

Background and objectives Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false-positive rates because of inherent laboratory and biologic variabilities of creatinine.Design, setting, participants, & measurements We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false-positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patient's true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria.Results Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false-positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%-8.1%), whereas patients with true serum creatinine $1.5 mg/dl (representing 21% of the clinical cohort) had a false-positive AKI diagnosis rate of 30.5% (interquartile range =30.1%-30.9%) versus 2.0% (interquartile range =1.9%-2.1%) in patients with true serum creatinine values ,1.5 mg/dl (P,0.001).Conclusions Use of small serum creatinine changes to diagnose AKI is limited by high false-positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies.

Utility of Electronic Medical Record Alerts to Prevent Drug Nephrotoxicity

“…For a nephrotoxic AKI alert, there are multiple potential points of failure. First, AKI itself may be misidentified on the basis of random variation in creatinine, changes in laboratory equipment standardization, or inclusion of individuals receiving dialysis (36). Second, nephrotoxic exposure may be misclassified by the alert if it unintentionally includes drugs that are not truly nephrotoxic, if it captures exposure to a drug that has already been discontinued, or if it fails to capture a drug due to a change in database coding for the agent (such as when a new manufacturer provides the agent to a hospital).…”

Endpoints for Clinical Trials of Acute Kidney Injury

“…Third, although creatinine variability is associated with increased mortality risk [8], this association is insufficient to define creatinine variability as equivalent to AKI. The combination of intra-patient biological variation and intrinsic analytic variability in serum creatinine is not insignificant, with greater variation in patients with underlying CKD [9,10]. In one analysis, creatinine variability resulted in a false-positive rate of AKI exceeding 30% among patients with a serum creatinine ≥1.5 mg/dL when the AKIN and KDI-GO definitions were employed [10].…”

“…The combination of intra-patient biological variation and intrinsic analytic variability in serum creatinine is not insignificant, with greater variation in patients with underlying CKD [9,10]. In one analysis, creatinine variability resulted in a false-positive rate of AKI exceeding 30% among patients with a serum creatinine ≥1.5 mg/dL when the AKIN and KDI-GO definitions were employed [10]. Finally, interventions may alter serum creatinine concentration independent of any nephroprotective effect (Fig.…”

Can Acute Kidney Injury Be Considered a Clinical Quality Measure?

“…There is a growing body of literature suggesting that contemporary definitions of AKI based on small changes in kidney function (e.g. KDIGO AKI stage 1) may be representative of biological and laboratory variation rather than AKI, particularly when relative changes are used in patients with low baseline serum creatinine, or when absolute increases are used in patients with high baseline creatinine [8,9,10]. Although these criteria may be useful for early identification of patients at risk of AKI, they are undesirable features of current AKI criteria for development of AKI as a clinically relevant outcome measure.…”