Objective  To explore the independent risk factors for the occurrence of acute kidney injury (AKI) caused by vancomycin (VAN) combined with piperacillin/tazobactam (PTZ) or carbapenem (CBP), and to construct and verify a nomogram prediction model for the risk factors.

Methods  The clinical data of all patients who received VAN combined with piperacillin tazobactam (VAN-PTZ) or carbapenem (VAN-CBP) in Wuxi Second People's Hospital from 2020 to 2024 and underwent blood drug concentration monitoring were retrospectively collected. The patients were divided into two groups according to whether they developed AKI. Randomly allocate the training set and the internal validation set in a 7∶3 ratio. After the initial screening of variables through LASSO regression, the Logistic regression model was used to analyze the risk factors AKI, and a nomogram model of AKI risk was constructed. The receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow calibration curve were respectively used to evaluate the discrimination and calibration of the predictive model. At the same time, combined with SHAP analysis, the relevant factors were analyzed to evaluate the contribution value of each variable.

Results  A total of 467 patients were included, among whom 95 cases (20.34%) developed AKI. Among them, 128 cases used VAN-PTZ, and 22 cases developed AKI. A total of 339 cases used VAN-CBP, and 73 cases developed AKI. The results of Logistic regression analysis and LASSO regression analysis showed that gender [female: OR=8.38, 95%CI (3.84, 18.28)], baseline creatinine value [OR=1.05, 95%CI (1.02, 1.07)], and the number of combined nephrotoxic drugs [combined use of two nephrotoxic drugs: OR=7.84, 95%CI (3.84, 16.02)], combined use of diuretics [OR=0.41, 95%CI (0.22, 0.76)] and trough plasma concentration of VAN [OR=1.07, 95%CI (1.05, 1.10)] were independent influencing factors for AKI induced by VAN-PTZ or VAN-CBP. Based on this, a nomogram model was constructed, the area under the curve (AUC) of the model in the training set and validation set was AUC=0.889[95%CI (0.83, 0.947)] and 0.848[95%CI (0.741, 0.955)], respectively, indicating good discrimination. The Hosmer-Lemeshow fit test showed good calibration (training set: P=0.657; validation set: P=0.789). SHAP analysis identified VAN blood drug concentration as the most critical predictor.

Conclusion  Gender, baseline creatinine value, numbers of combined nephrotoxic drugs, combined loop diuretics and trough plasma concentration of VAN are independent influencing factors for AKI induced by VAN-PTZ or VAN-CBP. The nomogram constructed based on these factors can effectively predict the risk of AKI in patients treated with VAN-PTZ and VAN-CBP.

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