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

Abstract

Abstract Estimated glomerular filtration rate (eGFR) based on creatinine (eGFRCreatinine) or cystatin C (eGFRCystatinC) 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. eGFRCreatinine and eGFRCystatinC were calculated using the LM-rev and CAPA equations, respectively. Gentamicin clearance was estimated using a population pharmacokinetic model and used as eGFRGentamicin. Agreement between eGFRs vs. eGFRGentamicin 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 eGFRGentamicin vs. eGFRCreatinine, and for eGFRGentamicin vs. eGFRCystatinC, 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 eGFRCreatinine, eGFRCystatinC and eGFRGentamicin 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, eGFRGentamicin 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.