Vancomycin Pharmacokinetics and Nephrotoxicity in Kidney Transplant Recipients: A Retrospective Cohort Study

Kidney transplant recipients (KTRs) frequently receive vancomycin for severe infections, but data on vancomycin pharmacokinetics (PK) and nephrotoxicity in this population remain limited. This retrospective cohort study included hospitalized adult KTRs who received vancomycin at the University of Michigan between 2007 and 2024, with a frequency-matched nontransplant comparison cohort. Population PK analysis was performed using nonlinear mixed-effects modeling. Nephrotoxicity was assessed using KDIGO criteria and 2009 vancomycin guideline definition. Risk factors were evaluated using multivariable logistic regression. The PK analysis included 1539 patients (469 KTRs, 1070 nontransplant). A one-compartment model adequately characterized vancomycin PK. Estimated clearance (CL) was substantially lower in KTRs than in nontransplant patients (1.5 vs. 3.9 L/h), and both creatinine clearance (CLcr) and KT status were significant covariates. The nephrotoxicity analysis included 1115 patients (303 KTRs, 812 nontransplant). KTRs had a higher crude incidence of nephrotoxicity under the KDIGO criteria (38.6% vs. 25.7%, p < 0.001) and the 2009 guideline definition (17.5% vs. 13.4%, p = 0.086). However, KT status was not independently associated with nephrotoxicity after adjustment. Sequential adjustment suggested that the higher unadjusted risk in KTRs was largely attenuated after accounting for baseline CLcr and concomitant nephrotoxin burden. These findings indicate that KTRs had lower vancomycin CL beyond that explained by CLcr alone and higher unadjusted rates of nephrotoxicity, which is associated with measurable clinical risk factors rather than KT status itself. Clinically, vancomycin therapy in KTRs may benefit from careful interpretation of CLcr-based dosing estimates, early individualized therapeutic drug monitoring, and active management of concomitant nephrotoxin exposure.