Innovative Use of Novel Biomarkers to Improve the Safety of Renally Eliminated and Nephrotoxic Medications

Abstract

Over the last decade, the discovery of novel renal biomarkers and research on their use to improve medication effectiveness and safety has expanded considerably. Pharmacists are uniquely positioned to leverage this new technology for renal assessment to improve medication dosing and monitoring. Serum cystatin C is a relatively new, inexpensive, functional renal biomarker that responds more quickly to changing renal function than creatinine and is not meaningfully affected by age, sex, skeletal muscle mass, dietary intake, or deconditioning. Cystatin C has been proposed as an adjunct or alternative to creatinine for glomerular filtration rate assessment and estimation of drug clearance. Tissue inhibitor of metalloproteinase-2·insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]) is a composite of two damage biomarkers released into the urine at a checkpoint in mitosis when renal cells undergo stress or sense a future risk of damage. Concentrations of [TIMP-2]·[IGFBP7] increase before a rise in serum creatinine is evident, thus providing insightful information for evaluation in the context of other patient data to predict the risk for impending kidney injury. This article provides a brief overview of novel renal biomarkers being used as a mechanism to improve medication safety including a discussion of cystatin C, as part of drug-dosing algorithms and specifically for vancomycin dosing, and the use of [TIMP-2]·[IGFBP7] for risk prediction in acute kidney injury and drug-induced kidney disease. Select cases of clinical experience with novel renal biomarkers are outlined, and lessons learned and future applications are described.

Prediction of the Renal Elimination of Drugs With Cystatin C vs Creatinine: A Systematic Review

“…Development of drug-specific algorithms are needed. 48 We recommend that for drugs with narrow therapeutic indices (eg, chemotherapeutics), high observed interpatient variability in drug levels (eg, blactams), or in high-risk populations (eg, elderly, critically ill), rigorous pharmacokinetic studies be performed and reported using standardized criteria. 46 Results from these studies could inform development of user-friendly dosing tools that then should be tested in pragmatic clinical trials.…”

Suboptimal Clinical Response Rates with Newer Antibiotics Among Patients with Moderate Renal Impairment: Review of the Literature and Potential Pharmacokinetic and Pharmacodynamic Considerations for Observed Findings

“…Furthermore, renal function may still be dynamic during the collection and assessment time. Novel renal biomarkers such as cystatin C have recently been proposed as alternative and potentially more accurate compounds to characterize renal function compared to S cr concentration . Alternatively, use of therapeutic drug monitoring for β‐lactams and other agents may be a means to assess clearance while ensuring adequate exposure .…”

“…Novel renal biomarkers such as cystatin C have recently been proposed as alternative and potentially more accurate compounds to characterize renal function compared to S cr concentration. 20 Alternatively, use of therapeutic drug monitoring for b-lactams and other agents may be a means to assess clearance while ensuring adequate exposure. 21 However, neither biomarker analysis nor therapeutic drug monitoring (for most antibiotics) is performed routinely, and best practices will need to be well defined before widespread implementation into clinical practice.…”

Innovations in Medication Safety: Services and Technologies to Enhance the Understanding and Prevention of Adverse Drug Reactions

“…Recently developed functional and damage biomarkers as possible early warning markers for AKI and, more specifically, drug‐associated AKI are gaining attention . The use of biomarkers in clinical practice is described by Barreto and colleagues . Drug‐associated QT c ‐interval prolongation is another safety concern.…”

“…20 The use of biomarkers in clinical practice is described by Barreto and colleagues. 21 Drug-associated QT c -interval prolongation is another safety concern. Muensterman and colleagues review the literature on the use of predictive analytics to assist with early warning of patients at risk for QT c -interval prolongation.…”