Attributable nephrotoxicity of vancomycin in critically ill patients: a marginal structural model study.

BACKGROUND: Although vancomycin nephrotoxicity is recognizable, critically ill patients have other potential reasons for acute kidney injury (AKI) and determining its attributable nephrotoxic risk in this population can be cumbersome. OBJECTIVES: To determine the risk of AKI attributable to vancomycin, controlling for baseline and time-dependent confounders. METHODS: Time-fixed and daily time-varying variables were extracted from a large public database. The exposures analysed were: (i) IV vancomycin; (ii) serum trough level greater than 15 and 20 mg/L; and (iii) concomitant exposure to vancomycin and piperacillin/tazobactam or other antipseudomonal ß-lactams. Censoring and exposure inverse probability of treatment weighting were calculated. Marginal structural models were plotted to evaluate AKI, severe AKI (stage 2/3) and need of renal replacement therapy (RRT). RESULTS: A total of 26 865 patients were included; 19.7% received vancomycin during ICU stay. After adjusting for fixed and time-variable confounders, vancomycin exposure was associated with AKI (HR = 1.24, 95% CI = 1.09-1.38), but not with severe AKI or need of RRT (HR = 1.05, 95% CI = 0.91-1.23 and HR = 0.97, 95% CI = 0.74-1.29, respectively). A serum trough level greater than 20 mg/L was associated with AKI (HR = 1.90, 95% CI = 1.52-2.30) and severe AKI (HR = 1.69, 95% CI = 1.31-2.19), but showed no statistically significant association with need of RRT (HR = 1.48, 95% CI = 0.92-2.56). The vancomycin + piperacillin/tazobactam combination was not associated with a greater risk than vancomycin alone. CONCLUSIONS: The attributable nephrotoxicity of vancomycin in critically ill patients is significantly lower than previously suggested and severe AKI is related to vancomycin only when trough serum levels are greater than 20 mg/L.

Kidney Disease Improving Global Outcomes or creatinine kinetics criteria in acute kidney injury: a proof of concept study.

BACKGROUND: It has been recently mathematically demonstrated that the percentage increase in serum creatinine (SCr) can delay acute kidney injury (AKI) diagnosis in patients with previous chronic kidney disease (CKD). Based on creatinine (Cr) kinetics, it was suggested a new AKI classification using absolute increase in SCr elevation over specified time periods. However, this classification has not been evaluated in clinical studies. METHODS: A prospective cohort study evaluated myocardial infarction patients during the first 7 days of hospital stay with daily SCr measurements. They were classified using Kidney Disease Improving Global Outcomes (KDIGO) and Cr kinetics systems. Both classifications were compared by net reclassification improvement (NRI) and area under the receiver operator characteristic (AuROC) curve regarding hospital mortality. RESULTS: A total of 584 patients were included, of which 34.1% had previous CKD. Patients had more AKI by KDIGO than by Cr kinetics criteria (25.7 versus 18.0%, P < 0.001) and 81 patients (13.9%) had different AKI severity classification. Patients with AKI by KDIGO criteria and non-AKI by Cr kinetics had higher hospital mortality rates than patients with non-AKI using both classifications [adjusted mortality odds ratios (ORs): 4.753; 95% confidence interval (CI): 1.119-9.023, P = 0.014]. In patients with previous CKD, NRI analysis was 6.2% favoring Cr kinetics criteria. However, there was no difference using the AuROC curve analysis. In patients with no previous CKD, NRI analysis was 33.0%, favoring KDIGO, and this was in accordance with a better AuROC curve (0.828 versus 0.664, P < 0.05). CONCLUSIONS: AKI classification proposed by a Cr kinetics model can be superior when diagnosing patients with previous CKD. However, KDIGO had a better performance in patients with no previous CKD.