Utilizing gentamicin concentrations to estimate glomerular filtration rate in intensive care unit patients

Estimated glomerular filtration rate (eGFR) based on creatinine (eGFR_Creatinine) or cystatin C (eGFR_CystatinC) require steady-state conditions and thus have limitations in intensive care unit (ICU) patients. Gentamicin is a potential exogenous marker for eGFR but poorly investigated. This retrospective study included adult ICU patients (≥ 18 years) treated with gentamicin and not on renal replacement therapy (RRT) at admission. eGFR_Creatinine and eGFR_CystatinC were calculated using the LM-rev and CAPA equations, respectively. Gentamicin clearance was estimated using a population pharmacokinetic model and used as eGFR_Gentamicin. Agreement between eGFRs vs. eGFR_Gentamicin and prediction of RRT and mortality for each eGFR were assessed. 254 patients were included of whom 11% (n = 28) received RRT later and 19% (n = 49) were dead at 30 days. The bias was 12 mL/min/1.73 m² and 8 mL/min/1.73 m², respectively, and the limits of agreement - 31-55 mL/min/1.73m² and - 46-62 mL/min/1.73m² for the agreement between eGFR_Gentamicin vs. eGFR_Creatinine, and for eGFR_Gentamicin vs. eGFR_CystatinC, respectively. The c-indexes for predicting RRT during ICU stay were 0.75 (0.64-0.86), 0.77 (0.66-0.88) and 0.80 (0.69-0.90) for eGFR_Creatinine, eGFR_CystatinC and eGFR_Gentamicin respectively, and for 30-day mortality 0.61 (0.52-0.70), 0.61 (0.52-0.70) and 0.63 (0.54-0.72) respectively. In ICU patients already receiving gentamicin, eGFR_Gentamicin derived from population PK models can be used to assess renal function and could potentially help improve dosing of other renally cleared drugs like the β-lactams during early phase of infections in the ICU.