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

Abstract

Serum cystatin C has been proposed as a kidney biomarker to inform drug dosing. We conducted a systematic review to synthesize available data for the association between serum cystatin C and drug pharmacokinetics, dosing, and clinical outcomes in adults (≥18 years). PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and Scopus were systematically searched from 1946 to September 2017 to identify candidate studies. Studies of cystatin C as a predictor for acute kidney injury or for management of contrast-associated acute kidney injury were excluded. Also, studies were excluded if drug concentrations were unavailable and if a reference standard for drug dosing (eg, serum creatinine) was not concurrently reported. The outcomes of interest included drug clearance (L/h), concentrations (mg/L), target level achievement (%), therapeutic failure (%), and drug toxicity (%). We included 28 articles that evaluated 16 different medications in 3455 participants. Vancomycin was the most well-studied drug. Overall, cystatin C-based estimated glomerular filtration rate (eGFR_{Cystatin C}) was more predictive of drug levels and drug clearance than eGFR_Creatinine. In only one study were target attainment and outcomes compared between 2 drug-dosing regimens, one based on eGFR_{Creatinine-Cystatin C} and one dosed with the Cockcroft-Gault creatinine clearance equation. Compared with eGFR_Creatinine, use of eGFR_{Cystatin C} to predict elimination of medications via the kidney was as accurate, if not superior, in most studies, but infrequently were data on target attainment or clinical outcomes reported. Drug-specific dosing protocols that use cystatin C to estimate kidney function should be tested for clinical application.