Cystatin C: A Primer for Pharmacists

Abstract

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.

Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Kidney Function

“…38 Production of S cys is dependent on cell turnover, which is disrupted in hypothyroidism and hyperthyroidism, which can lead to overestimation and underestimation of eGFR, respectively. 38 Despite these limitations, the international federation for clinical chemistry working group has established human serum certified reference materials and are advancing global standardization. 39 The next generation of eGFR based on endogenous biomarkers will require prospective evaluation of S cys and the combination of S cys with S cr .…”

“…Simulations demonstrate that the eGFR based on the combination of these biomarkers better predicts ceftriaxone exposures and doses than body weight 36 . Limitations do exist with use of S cys due to underestimation of eGFR in patients with obesity, malignancy, high‐dose corticosteroid use, kidney transplant recipients, and in patients that smoke 38 . Production of S cys is dependent on cell turnover, which is disrupted in hypothyroidism and hyperthyroidism, which can lead to overestimation and underestimation of eGFR, respectively 38 .…”

“…Limitations do exist with use of S cys due to underestimation of eGFR in patients with obesity, malignancy, high‐dose corticosteroid use, kidney transplant recipients, and in patients that smoke 38 . Production of S cys is dependent on cell turnover, which is disrupted in hypothyroidism and hyperthyroidism, which can lead to overestimation and underestimation of eGFR, respectively 38 . Despite these limitations, the international federation for clinical chemistry working group has established human serum certified reference materials and are advancing global standardization 39 .…”

Parasite Cystatin: Immunomodulatory Molecule with Therapeutic Activity against Immune Mediated Disorders

“…Cystatin C is particularly important in assessing kidney functions and is recommended by regulatory agencies for the evaluation of the glomerular filtration rate [ 51 ]. Serum levels of cystatin C in association with serum creatinine, serve as a prognosis and/or diagnostic biomarker for assessing kidney function [ 52 ]. Type-2 cystatins are shown to take part in several immune-regulatory activities [ 42 ].…”

Modeling Kinetic Glomerular Filtration Rate in Adults with Stable and Unstable Kidney Function: Vancomycin as the Motivating Example

“…7 Although cystatin C improves the precision of kidney function estimation with a modified CKD-EPI function, it is not a widely accessible assay and not included in any product label to guide drug dosing. 8 Translation of a single-point measurement of serum creatinine into clearance (CL) is based on the assumption of homeostasis, i.e., production or systemic input of creatinine and the rate of creatinine elimination is constant and equivalent. 9 A corollary to this estimation method occurs with continuous infusion drug dosing, where the rate of infusion (Ro) divided by the steady-state concentration (Css) equals clearance (CL).…”