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Abstract: FR-PO216

Glomerular Filtration Rate Equations for Drug Dosing: Discordance by BMI and Age

Session Information

  • Pharmacology
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

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

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

Authors

  • Lyu, Beini, Johns Hopkins University, Baltimore, Maryland, United States
  • Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
  • Chang, Alex R., Geisinger Health, Danville, Pennsylvania, United States
  • Nolin, Thomas D., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Coresh, Josef, Johns Hopkins University, Baltimore, Maryland, United States
  • Grams, Morgan, New York University, New York, New York, United States
  • Shin, Jung-Im, Johns Hopkins University, Baltimore, Maryland, United States
Background

Historically, different methods to estimate glomerular filtration rate (GFR) have been used for drug development, labeling for drug dosing, and clinical practice. Substantial differences in GFR estimated from different equations may prevent optimal drug dosing.

Methods

We analyzed 29,564 patients with atrial fibrillation (AF) who had serum creatinine, weight, and height measurements in Geisinger health system between 2005-2019 (mean age 76yrs, mean body mass index [BMI] 29.5 kg/m2). We compared differences among three GFR estimates by BMI and age: Cockcroft-Gault estimated creatinine clearance (eClCr; unit: mL/min), CKD-EPI 2021 (eGFR, mL/min/1.73 m2), and non-indexed CKD-EPI 2021 (neGFR, mL/min). To quantify potential impact on drug dosing, we estimated the proportion of discordance in recommended rivaroxaban dose by different GFR estimates among patients with eGFR 30-60 mL/min/1.73 m2. The FDA label for rivaroxaban recommends a reduced dose in eClCr <50 mL/min.

Results

The differences among the three estimates varied by BMI and by age: for example, eClCr was higher than eGFR and neGFR among patients with BMI ≥40 kg/m2 (mean: eClCr 117.8 mL/min, eGFR 65.8 mL/min/1.73 m2, and neGFR 89.4 mL/min); eClCr was lower than eGFR and neGFR among patients ≥85 years (mean: eClCr 38.6 mL/min, eGFR 51.6 mL/min/1.73 m2, neGFR 51.9 mL/min). Rivaroxaban dosing discordance varied by BMI and age as well: for example, among patients with BMI ≥40 kg/m2, 40-60% of patients would need a reduced dose of rivaroxaban by eGFR and 15-20% would need a reduced dose by neGFR whereas standard dose would be recommended by eClCr across the age groups (Figure).

Conclusion

eClCr, eGFR, and neGFR values could differ substantially depending on body size and age, potentially resulting in substantial drug dosing discordance.

Funding

  • NIDDK Support