TY - JOUR
T1 - Development of biomarker combinations for postoperative acute kidney injury via Bayesian model selection in a multicenter cohort study
AU - Meisner, Allison
AU - Kerr, Kathleen F.
AU - Thiessen-Philbrook, Heather
AU - Wilson, Francis Perry
AU - Garg, Amit X.
AU - Shlipak, Michael G.
AU - Kavsak, Peter
AU - Whitlock, Richard P.
AU - Coca, Steven G.
AU - Parikh, Chirag R.
N1 - Funding Information:
The research was supported by the NIH grant R01HL085757 (CRP) to fund the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) Consortium to study novel biomarkers of acute kidney injury in cardiac surgery. AM is supported by the NIH grant F31DK108356. CRP is also supported by NIH grant K24DK090203. SGC is supported by National Institutes of Health Grants K23DK080132 and R01DK096549. SGC and CRP are also members of the NIH-sponsored ASsess, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Consortium (U01DK082185). This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. No endorsement by ICES or the Ontario Ministry of Health and Long-Term Care is intended or should be inferred. The opinions, results, and conclusions reported in this article are those of the authors and are independent of the funding sources.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/1/12
Y1 - 2018/1/12
N2 - Background: Acute kidney injury (AKI) is a frequent complication of cardiac surgery. We sought prognostic combinations of postoperative biomarkers measured within 6 h of surgery, potentially in combination with cardiopulmonary bypass time (to account for the degree of insult to the kidney). We used data from a large cohort of patients and adapted methods for developing biomarker combinations to account for the multicenter design of the study. Methods: The primary endpoint was sustained mild AKI, defined as an increase of 50% or more in serum creatinine over preoperative levels lasting at least 2 days during the hospital stay. Severe AKI (secondary endpoint) was defined as a serum creatinine increase of 100% or more or dialysis during hospitalization. Data were from a cohort of 1219 adults undergoing cardiac surgery at 6 medical centers; among these, 117 developed sustained mild AKI and 60 developed severe AKI. We considered cardiopulmonary bypass time and 22 biomarkers as candidate predictors. We adapted Bayesian model averaging methods to develop center-adjusted combinations for sustained mild AKI by (1) maximizing the posterior model probability and (2) retaining predictors with posterior variable probabilities above 0.5. We used resampling-based methods to avoid optimistic bias in evaluating the biomarker combinations. Results: The maximum posterior model probability combination included plasma N-terminal-pro-B-type natriuretic peptide, plasma heart-type fatty acid binding protein, and change in serum creatinine from before to 0-6 h after surgery; the median probability combination additionally included plasma interleukin-6. The center-adjusted, optimism-corrected AUCs for these combinations were 0.80 (95% CI: 0.78, 0.87) and 0.81 (0.78, 0.87), respectively, for predicting sustained mild AKI, and 0.81 (0.76, 0.90) and 0.83 (0.76, 0.90), respectively, for predicting severe AKI. For these data, the Bayesian model averaging methods yielded combinations with prognostic capacity comparable to that achieved by standard frequentist methods but with more parsimonious models. Conclusions: Pending external validation, the identified combinations could be used to identify individuals at high risk of AKI immediately after cardiac surgery and could facilitate clinical trials of renoprotective agents.
AB - Background: Acute kidney injury (AKI) is a frequent complication of cardiac surgery. We sought prognostic combinations of postoperative biomarkers measured within 6 h of surgery, potentially in combination with cardiopulmonary bypass time (to account for the degree of insult to the kidney). We used data from a large cohort of patients and adapted methods for developing biomarker combinations to account for the multicenter design of the study. Methods: The primary endpoint was sustained mild AKI, defined as an increase of 50% or more in serum creatinine over preoperative levels lasting at least 2 days during the hospital stay. Severe AKI (secondary endpoint) was defined as a serum creatinine increase of 100% or more or dialysis during hospitalization. Data were from a cohort of 1219 adults undergoing cardiac surgery at 6 medical centers; among these, 117 developed sustained mild AKI and 60 developed severe AKI. We considered cardiopulmonary bypass time and 22 biomarkers as candidate predictors. We adapted Bayesian model averaging methods to develop center-adjusted combinations for sustained mild AKI by (1) maximizing the posterior model probability and (2) retaining predictors with posterior variable probabilities above 0.5. We used resampling-based methods to avoid optimistic bias in evaluating the biomarker combinations. Results: The maximum posterior model probability combination included plasma N-terminal-pro-B-type natriuretic peptide, plasma heart-type fatty acid binding protein, and change in serum creatinine from before to 0-6 h after surgery; the median probability combination additionally included plasma interleukin-6. The center-adjusted, optimism-corrected AUCs for these combinations were 0.80 (95% CI: 0.78, 0.87) and 0.81 (0.78, 0.87), respectively, for predicting sustained mild AKI, and 0.81 (0.76, 0.90) and 0.83 (0.76, 0.90), respectively, for predicting severe AKI. For these data, the Bayesian model averaging methods yielded combinations with prognostic capacity comparable to that achieved by standard frequentist methods but with more parsimonious models. Conclusions: Pending external validation, the identified combinations could be used to identify individuals at high risk of AKI immediately after cardiac surgery and could facilitate clinical trials of renoprotective agents.
KW - Acute kidney injury
KW - Biomarkers combinations
KW - Cardiac surgery
KW - Prognostic
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U2 - 10.1186/s40364-018-0117-z
DO - 10.1186/s40364-018-0117-z
M3 - Article
C2 - 29344362
AN - SCOPUS:85049632878
SN - 2050-7771
VL - 6
JO - Biomarker Research
JF - Biomarker Research
IS - 1
M1 - 3
ER -