The TMLE aims at targeting our estimation in a way that the optimal bias/variance Lenalidomide clinical tradeoff is achieved for the parameter of interest.Our study has several limitations. First, it was performed in a tertiary center with wide experience in medical and surgical treatment of patients with IE, potentially limiting the external validity. Second, our definition of AKI was based on serum creatinine level and did not include urine output. Third, we only have limited information on transfusion requirements. We were only able to evaluate the risk associated with peri-operative transfusion, but not the amount of blood transfused, nor the risk associated with pre- or post-operative transfusion. Fourth, the results apply to a selected population of patients suitable for surgery.

Finally, despite the SuperLearner procedure, which is intended to optimize the prediction, our predictive performance was in fact limited, with an AUROC of 0.760 (95% CI 0.694, 0.826) for the SuperLearner weighted algorithm. Improved predictive performance might first be achieved by expanding the library of candidate algorithms, as the SuperLearner is at least as good as the best of its library. Hence, it remains to be investigated if a more aggressive library will result in further improvements. If not, one should consider expanding the set of predictive variables considered, including, potentially, specific kidney biomarkers.ConclusionsThis study adds evidence to the current literature suggesting that post-operative AKI following cardiac surgery with cardiopulmonary bypass results from additive hits to the kidney.

It also identified several modifiable risk factors of post-operative AKI such as treatment with vancomycin or aminoglycosides or pre-operative anemia. Development of post-operative AKI was associated with in-hospital mortality. Prevention or correction of these risk factors may improve outcome in patients with IE undergoing cardiac surgery.Key messages?>50% patients undergoing cardiac surgery for IE develop post-operative AKI?We identified six risk factors for post-operative AKI, most being treatment-related, including vancomycine and aminoglycoside administration, and contrast agent.?Pre-operative anemia was associated with an increased risk of post-operative AKI?Post-operative AKI was associated with an increased risk of death.

AbbreviationsAIC: Akaike information criterion; AKI: Acute kidney injury; AKIN: Acute kidney injury network; AUROC: Area under the receiver operating curve; CPB: Cardiopulmonary bypass; COPD: Chronic obstructive pulmonary disease; GFR: Glomerular filtration rate; IE: Infective endocarditis; LVEF: Left ventricular ejection Carfilzomib fraction; MDRD: Modification of diet in renal disease; NYHA: New York Heart Association; OR: Odds ratio; RBC: Red blood cell; RR: Relative risk; RRT: Renal replacement therapy; TMLE: Targeted maximum likelihood estimation.