Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring is serum creatinine (SCr)-based estimation equations. Yet, SCr has known limitations including its insensitivity to underlying changes in kidney function and the numerous non-kidney factors that are incompletely accounted for in equations to estimate glomerular filtration rate (eGFR). Serum cystatin C (cysC) is a biomarker that can serve as an adjunct or alternative to SCr to evaluate kidney function for drug dosing. Pharmacists must be educated about the strengths and limitations of cysC prior to applying it to medication management. Not all patient populations have been studied and some evaluations demonstrated large variations in the relationship between cysC and GFR. Use of eGFR equations incorporating cysC should be reserved for drug management in scenarios with demonstrated outcomes, including to improve pharmacodynamic target attainment for antibiotics or reduce drug toxicity. This article provides an overview of cysC, discusses evidence around its use in medication dosing and in special populations, and describes practical considerations for application and implementation.
Itraconazole is well known for carrying a black-box warning for new or worsening congestive heart failure. Single cases of other cardiac-and fluid-related disturbances have been reported periodically since its issuance. We describe a large cohort of patients on itraconazole experiencing a breadth of cardiac-and fluid-related toxicities, ranging from new-onset hypertension to cardiac arrest. A retrospective, singlecenter, large case series at a large tertiary medical center was conducted. Patients with itraconazole and cardiac toxicitydincluding hypertension, cardiomyopathy, reduced ejection fraction, and edemadin medical record between January 1, 1999, and May 21, 2019, were identified and assigned a Naranjo score; 31 patients were included with a Naranjo score of 5 or higher. There were slightly more male subjects than female subjects, average age was 66, and all subjects were Caucasian. Median time until presentation of adverse effects was 4 weeks (range: 0.3 to 104 weeks). Most common symptom was edema (74% of patients), followed by heart failure without and with preserved ejection fraction (19.4% and 22.6% of patients, respectively). Worsening or new hypertension was also common (25.8% of patients). Rarer were pulmonary edema, pericardial effusion, and cardiac arrest that occurred in 1 patient. In most cases, clinicians stopped itraconazole (74%) or decreased itraconazole dose (19%), resulting in improvement or resolution of symptoms. In 4 cases, the adverse effect did not resolve. Itraconazole can cause a range of possible serious cardiac and fluid-associated adverse events. Dose decrease or cessation usually resulted in symptomatic improvement or reversal.
The use of the kidney function biomarker cystatin C (cysC) can improve the accuracy of vancomycin dosing for target trough attainment in non-obese patients. It is unknown whether cysC can also improve vancomycin target trough attainment in overweight and obese patients. We conducted a retrospective observational study of overweight or obese hospitalized adults with stable renal function administered intravenous vancomycin between January 2011 and July 2019. Linear regression models were used to predict initial steady-state vancomycin troughs using several factors, including various cysC- and serum creatinine (SCr)-based estimates of kidney function. We compared the predicted proportion of patients within the target trough range (10-20mg/L) using the derived models to that observed from usual care. Of the 200 included patients, the mean trough level was 15 ± 6.3 mg/L. The optimal model to predict the initial trough included both cysC and SCr (R2= 0.48) rather than either biomarker alone. This model predicted 79% (95% CI: 73%-85%) of troughs could be between 10 - 20mg/L compared to the 62% observed in clinical practice (p < 0.001), a 1.3-fold increase. This study is the first to examine the role of cysC in predicting vancomycin levels in an exclusively overweight or obese population. While dosing models based on cysC appear promising in this setting, prospective validation is needed.
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