Cystatin C as a potential biomarker for dosing of renally excreted drugs

Abstract

The objective of the present study was to review the available pharmacokinetic evidence for the utility of cystatin C (CysC) as a marker of renal function to predict the dose of renally excreted drugs.The bibliographic search used PubMed and EMBASE databases, from its inception through to January 2014, with the following keywords 'pharmacokinetics' and 'cystatin C'.Sixteen pharmacokinetic publications were identified and seven drugs primarily excreted by the kidney were studied. Among them, only one study was performed in children, the others were performed in adults and/or elderly subjects, either healthy volunteers or patients with variable clinical conditions, such as cystic fibrosis and cancer. Most of studies (n = 13/16) demonstrated that CysC was better correlated with clearance/trough concentration of evaluated drugs compared with creatinine.Our review supports that CysC is a good marker of renal function to predict dose of renally excreted drugs. Efforts should be made to evaluate the impact of CysC in special populations in order to define its clinical value in dosing optimization.

Drug Interactions in the Treatment of Malignancy in HIV-Infected Patients

“…Furthermore, in an analysis of 16 studies that directly compared the impact of CysC and of creatinine clearance on drug elimination, 13 found CysC to be superior [59]. These included studies of topotecan and carboplatin clearance, which correlated better with CysC than with creatinine clearance, and confirmed findings from a previous study in oncology patients [60].…”

“…This does not reflect a reduction in the glomerular filtration rate (GFR) and should be carefully interpreted in the setting of potentially nephrotoxic chemotherapy drugs [58]. Several studies and meta-analyses have found that cystatin C (CysC) significantly outperformed serum creatinine for the monitoring of GFR in critically ill patients [59].…”

Novel Kidney Injury Biomarkers Among Anabolic Androgenic Steroids Users - Evidence of Subclinical Kidney Disease

“…In the present study there were also higher creatinine levels among AAS users in comparison with non-users. Cystatin C, although considered a slightly better renal function biomarker than creatinine (22), did not show significant difference when comparing AAS users vs. non-users. The levels of the new biomarker MCP-1 were significantly higher among AAS users in our study, suggesting subclinical renal inflammation, which can be directly caused by AAS use, including the possibility of chronic interstitial nephritis.…”

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

“…The data for the use of serum cystatin C to estimate GFR in patients with stable renal function and consequently drug clearance are somewhat limited but promising. Several renally eliminated medications have been tested including antimicrobial agents, cardiovascular drugs, and chemotherapeutics, but strategies to implement the use of this biomarker routinely at the bedside are lacking . In the case of vancomycin, serum cystatin C or the associated eGFR better predicted vancomycin clearance than creatinine in pharmacokinetic models, especially among those with altered skeletal muscle mass …”

“…Several renally eliminated medications have been tested including antimicrobial agents, cardiovascular drugs, and chemotherapeutics, but strategies to implement the use of this biomarker routinely at the bedside are lacking. [22][23][24][25][26][27][28][29] In the case of vancomycin, serum cystatin C or the associated eGFR better predicted vancomycin clearance than creatinine in pharmacokinetic models, especially among those with altered skeletal muscle mass. [30][31][32][33][34][35] Case Study: Cystatin C for Vancomycin Dosing…”