False-Positive Rate of AKI Using Consensus Creatinine-Based Criteria.
OBJECTIVE
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.


METHODS
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.
Renal Electrolyte and Hypertension Division, Department of Medicine and.
Jennie
J
Lin
Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, New York; and.
Hilda
H
Fernandez
Pulmonary, Allergy, and Critical Care Division, Department of Medicine and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
Michael G S
MG
Shashaty
Renal Electrolyte and Hypertension Division, Department of Medicine and.
Dan
D
Negoianu
Sections of Cardiology and.
Jeffrey M
JM
Testani
Renal Electrolyte and Hypertension Division, Department of Medicine and.
Jeffrey S
JS
Berns
Nephrology and Program of Applied Translational Research, Department of Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut.
Chirag R
CR
Parikh
Nephrology and Program of Applied Translational Research, Department of Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut francis.p.wilson@yale.edu.
F Perry
FP
Wilson
D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003198:Computer Simulation; D032921:Consensus; D003404:Creatinine / Q000097:blood*; D003951:Diagnostic Errors / Q000706:statistics & numerical data*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011446:Prospective Studies
D015415:Biomarkers; D003404:Creatinine
acute renal failure; creatinine; epidemiology and outcomes; misdiagnosis; survival