Kidney Week

Abstract: TH-PO0827

Determinants of Vancomycin Clearance During CRRT: A Longitudinal Analysis of Patient- and Machine-Level Factors

Session Information

• Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Rajaofetra, Kameron, University of California San Diego, La Jolla, California, United States

Kameron Rajaofetra

• Mehta, Ravindra L., University of California San Diego, La Jolla, California, United States

Ravindra L. Mehta, MD, MBBS, DM, FASN

• Awdishu, Linda, University of California San Diego, La Jolla, California, United States

Linda Awdishu, PharmD, MA, FASN

Background

Vancomycin (VAN) is frequently used in critically ill patients receiving continuous renal replacement therapy (CRRT), yet drug exposure remains highly variable despite protocolized dosing. Current CRRT-based dosing approaches inadequately account for dynamic changes in drug clearance over time. We evaluated patient- and CRRT-related predictors of VAN clearance and quantified the relative contribution of each to overall variability.

Methods

We conducted a retrospective cohort study of critically ill adults receiving VAN during CRRT at UC San Diego Health (January 1, 2017–December 31, 2018). Demographic variables, clinical factors (including ECMO, ventilation), and CRRT parameters (effluent dose, blood flow rate, replacement fluid modality, anticoagulation) as well as filter performance metrics (transmembrane pressure [TMP], filter lifespan) were collected. Data was made cleaned using R 4.5.3. VAN clearance was estimated from serum concentrations using a pharmacokinetic software, PrecisePK, and a linear mixed-effects model over the first 100 hours of CRRT with patient-level random intercepts to identify predictors of clearance and split variance between patient- and CRRT-level factors.

Results

95 patients were included with mean (SD) age 57.5(15.6) years; 74% male; mean (SD) BMI 29.0(7.7) kg/m2. VAN pharmacokinetic parameters for the cohort were mean (SD): Vd_ss 105.2 (103.5) L; T_1/2 beta 94.8 (85.9) h, CLmax 40.4(8.1) mL/min/kg; Cloff_rrt 0.9(0.5) mL/min/kg. VAN clearance declined over time on CRRT (p<0.001) and was driven by patient-level variability (ICC = 0.958), with CRRT parameters explaining minimal variance (marginal R² = 0.07). Higher TMP was associated with reduced clearance (β =−0.008 per mmHg, p=0.031), consistent with declining filter performance. Filter lifespan demonstrated a nonlinear relationship with clearance, with lower clearance observed in prolonged filter use (>96 hours).

Conclusion

VAN clearance during CRRT declines over time and is strongly influenced by patient-specific factors, with minimal contribution from CRRT settings. These findings challenge CRRT-based dosing paradigms and support therapeutic drug monitoring strategies that prioritize individualized pharmacokinetics over fixed, machine-based dosing adjustments.