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

Abstract

IntroductionSerum 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.MethodsThis 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.ResultsOf 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 (R2 = 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).ConclusionsVancomycin 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.

Clinical decision support for drug related events: Moving towards better prevention

“…This biomarker shows promise for early detection and earlier intervention. Additionally, a study by Frazee et al[56] shows that biomarkers can also improve drug dosing. This study showed that vancomycin dosing in the ICU can be improved 2.5 fold when using cystatin C and serum creatinine to estimate GFR as opposed to just serum creatinine alone[56].…”

Pharmacokinetic/Pharmacodynamic Analysis for Doripenem Regimens in Intensive Care Unit Patient

“…25) In addition, estimated GFR or Ccr calculated using cystatin C predicts vancomycin trough levels better than Ccr calculated by Cockcroft-Gault formula. 26,27) In fact, the mean estimated GFR (69.1±33.1 mL/min) 26) or Ccr (46.6±24.6 mL/min) 27) calculated using cystatin C levels before DRPM administration tended to be lower than the mean Ccr calculated by Cockcroft-Gault formula (76.0±37.4 mL/min). Thus, the dosage regimen of DRPM, a renally excreted drug, for ICU patients may need to be also established by stratifying renal function based on GFR or Ccr estimated using cystatin C.…”

Adaptation posologique des médicaments et fonction rénale : quel(s) estimateur(s) faut-il choisir ?

“…Les é tudes sur la pré diction de la clairance de mé dicaments (le plus souvent les aminoglycosides et la vancomycine) par les diffé rentes é quations sont plus rares et les ré sultats contradictoires [48,51,58,76,[84][85][86][87][88][89]. Enfin, une autre façon d'illustrer les é ventuelles discordances entre les é quations est de reprendre des donné es d'é tudes cliniques observationnelles ou interventionnelles et de vé rifier si les conclusions des dites é tudes resteraient identiques en utilisant l'é quation de Cockcroft (comme cela a é té fait de prime abord dans la plupart des é tudes) ou une autre é quation.…”

“…Notons é galement que des é tudes commencent à être publié es sur l'inté rêt de nouveaux biomarqueurs, le plus avancé é tant la cystatine C [83,84,88,89,110].…”