Serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients: a cohort study

Abstract

Introduction: Serum cystatin C can improve glomerular filtration rate (GFR) estimation over creatinine alone, but whether this translates into clinically relevant improvements in drug dosing is unclear.

Methods: This prospective cohort study enrolled adults receiving scheduled intravenous vancomycin while hospitalized at the Mayo Clinic in 2012. Vancomycin dosing was based on weight, serum creatinine with the Cockcroft-Gault equation, and clinical judgment. Cystatin C was later assayed from the stored serum used for the creatinine-based dosing. Vancomycin trough prediction models were developed by using factors available at therapy initiation. Residuals from each model were used to predict the proportion of patients who would have achieved the target trough with the model compared with that observed with usual care.

Results: Of 173 patients enrolled, only 35 (20%) had a trough vancomycin level within their target range (10 to 15 mg/L or 15 to 20 mg/L). Cystatin C-inclusive models better predicted vancomycin troughs than models based upon serum creatinine alone, although both were an improvement over usual care. The optimal model used estimated GFR by the Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) creatinine-cystatin C equation (R(2) = 0.580). This model is expected to yield 54% (95% confidence interval 45% to 61%) target trough attainment (P <0.001 compared with the 20% with usual care).

Conclusions: Vancomycin dosing based on standard care with Cockcroft-Gault creatinine clearance yielded poor trough achievement. The developed dosing model with estimated GFR from CKD-EPIcreatinine-cystatin C could yield a 2.5-fold increase in target trough achievement compared with current clinical practice. Although this study is promising, prospective validation of this or similar cystatin C-inclusive dosing models is warranted.

Figure 1

Patient enrollment flowchart.

Figure 2

Overview of the study protocol. Factors available at baseline, prior to the first vancomycin dose, were used to develop vancomycin trough level prediction models. Steady-state vancomycin trough adequacy, prior to the fourth dose, was determined according to individualized target ranges based on suspected or documented source(s) of infection.

Figure 3

Graphical representation of the expected improvement in vancomycin trough target levels with application of the Chronic Kidney Disease Epidemiology Collaborative models. Predicted trough for each model (x-axis) versus actual trough or versus the expected trough when targeting 15 mg/L with the model (y-axis) for model 5 (a,b), model 6 (c,d), and model 7 (e,f). The improvement in the proportion that would have an expected trough of 10 to 20 mg/L for each model is also shown. The more refined analysis targeting a trough of 10 to 15 or 15 to 20 mg/L (depending on the clinical indication for treatment) is presented in the text and tables.

Figure 4

Association between vancomycin trough concentrations and estimated glomerular filtration rate (GFR) with CKD-EPI_{creatinine-cystatin C}. A significant inverse relationship exists between GFR and vancomycin troughs (P <0.0001). Patients with a GFR of more than 120 mL/min rarely reached the minimum acceptable trough of 10 mg/L. CKD-EPI, Chronic Kidney Disease Epidemiology Collaborative.