RESUMO
RATIONALE & OBJECTIVE: Sepsis-associated acute kidney injury often leads to acute kidney disease (AKD), predisposing patients to long-term complications such as chronic kidney disease (CKD), kidney failure with replacement therapy (KFRT), or mortality. Risk stratification of patients with AKD represents an opportunity to assist with prognostication of long-term kidney complications. STUDY DESIGN: Single-center retrospective cohort. SETTING & PARTICIPANTS: 6,290 critically ill patients admitted to the intensive care unit with severe sepsis or septic shock. Patients were separated into cohorts based on incident acute kidney injury or not, and survivors identified who were alive and free of KFRT up to 90 days. PREDICTORS: AKD stage (0A, 0C, or ≥1) using the last serum creatinine concentration available by discharge or up to 90 days postdischarge. OUTCOME: Time to development of incident CKD, progression of CKD, KFRT, or death. ANALYTICAL APPROACH: Multivariable Cox proportional hazards models. RESULTS: Patients surviving kidney injury associated with sepsis often fail to return to baseline kidney function by discharge: 577/1,231 (46.9%) with stage 0C or 1 or greater AKD. AKD stage was significantly associated with the composite primary outcome. Stages 0C AKD and 1 or greater AKD were significantly and progressively associated with the primary outcome when compared with stage 0A AKD (adjusted HR [aHR], 1.74; 95% CI, 1.32-2.29, and aHR, 3.25; 95% CI, 2.52-4.20, respectively). Additionally, stage 1 or greater AKD conferred higher risk above stage 0C AKD (aHR, 1.87; 95% CI, 1.44-2.43). CKD incidence or progression and KFRT, more so than mortality, occurred with greater frequency in higher stages of AKD. LIMITATIONS: Retrospective design, single center, exclusion of patients with KFRT within 90 days of discharge, potential ascertainment bias, and inability to subclassify above AKD stage 1. CONCLUSIONS: Risk stratification using recommended AKD stages at hospital discharge or shortly thereafter associates with the development of long-term kidney outcomes following sepsis-associated acute kidney injury.
RESUMO
BACKGROUND: Early attainment of target area under the curve (AUC) to minimum inhibitory concentration (MIC) ratios have been associated with clinical success, as well as lower incidence of acute kidney injury (AKI), in patients receiving vancomycin for methicillin-resistant Staphylococcus aureus (MRSA). Critically ill patients are particularly vulnerable to poor outcomes from infection and face multiple risk factors for AKI, thus early precision dosing of vancomycin is vital in this population. We hypothesized that a personalized dosing approach, using vancomycin levels obtained after the first dose to guide further dosing, would be superior to empiric dosing in terms of AUC target attainment assessed at steady state (SS). METHODS: A retrospective cohort study of 66 critically ill adult patients admitted to the medical intensive care unit without AKI and receiving vancomycin with at least two SS concentrations obtained for AUC calculation was performed. Patients were separated into cohorts based on whether they had two concentrations assessed after the first dose of vancomycin and were subsequently dosed based on personalized pharmacokinetic calculations (first-dose kinetics) or whether they were empirically dosed using population estimates. The primary outcome was AUC target attainment (400-600 mg hour/L) at SS. RESULTS: Compared with patients receiving empiric dosing by population estimates, using first-dose kinetics to guide subsequent dosing resulted in significantly greater AUC target attainment at SS (58.6% first-dose vs 32.4% empiric; p=0.033). Patients dosed empirically yielded more variable AUC values across a wide range compared with the first-dose kinetics group (coefficient of variation 40.7% empiric vs 26.1% first-dose). There was no difference in AKI up to 48 hours after SS concentrations between the two dosing schemes. CONCLUSIONS: A dosing strategy using two vancomycin serum concentrations after the first dose and calculating personalized pharmacokinetic parameters to guide subsequent dosing is associated with greater AUC target attainment at SS compared with empiric dosing of vancomycin in critically ill adults with relatively stable renal function.
