Latent variable modeling improves AKI risk factor identification and AKI prediction compared to traditional methods.
BACKGROUND
Acute kidney injury (AKI) is diagnosed based on postoperative serum creatinine change, but AKI models have not consistently performed well, in part due to the omission of clinically important but practically unmeasurable variables that affect creatinine. We hypothesized that a latent variable mixture model of postoperative serum creatinine change would partially account for these unmeasured factors and therefore increase power to identify risk factors of AKI and improve predictive accuracy.


METHODS
We constructed a two-component latent variable mixture model and a linear model using data from a prospective, 653-subject randomized clinical trial of AKI following cardiac surgery (NCT00791648) and included established AKI risk factors and covariates known to affect serum creatinine. We compared model fit, discrimination, power to detect AKI risk factors, and ability to predict AKI between the latent variable mixture model and the linear model.


RESULTS
The latent variable mixture model demonstrated superior fit (likelihood ratio of 6.68 × 1071) and enhanced discrimination (permutation test of Spearman's correlation coefficients, p < 0.001) compared to the linear model. The latent variable mixture model was 94% (-13 to 1132%) more powerful (median [range]) at identifying risk factors than the linear model, and demonstrated increased ability to predict change in serum creatinine (relative mean square error reduction of 6.8%).


CONCLUSIONS
A latent variable mixture model better fit a clinical cohort of cardiac surgery patients than a linear model, thus providing better assessment of the associations between risk factors of AKI and serum creatinine change and more accurate prediction of AKI. Incorporation of latent variable mixture modeling into AKI research will allow clinicians and investigators to account for clinically meaningful patient heterogeneity resulting from unmeasured variables, and therefore provide improved ability to examine risk factors, measure mechanisms and mediators of kidney injury, and more accurately predict AKI in clinical cohorts.
Department of Anesthesiology, Vanderbilt University Medical Center, 1211 21st Avenue South, Nashville, TN, 37205, USA.
Loren E
LE
Smith
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
Derek K
DK
Smith
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
Jeffrey D
JD
Blume
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.|Division of Nephrology and Hypertension, Vanderbilt Center for Kidney Disease and Integrated Program for AKI Research, Vanderbilt University Medical Center, Nashville, TN, USA.
Edward D
ED
Siew
Department of Anesthesiology, Vanderbilt University Medical Center, 1211 21st Avenue South, Nashville, TN, 37205, USA. frederic.t.billings@vanderbilt.edu.|Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. frederic.t.billings@vanderbilt.edu.
Frederic T
FT
Billings
D058186:Acute Kidney Injury / Q000453:epidemiology* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D006348:Cardiac Surgical Procedures; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011183:Postoperative Complications / Q000453:epidemiology* / Q000378:metabolism; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
D003404:Creatinine
Acute kidney injury; Creatinine; Latent variable; Mixture model; Prediction; Risk factor