Morten Baltzer Houlind, Ida Klitzing Storgaard, L B Christensen, Rikke L Nielsen, Aino Leegaard Andersen, Olivia Bornæs, Helle Gybel Juul‐Larsen, Anne Walls, Johnny K H Dang, Baker Nawfal Jawad, Izzet Altintas, Sergio Luis-Lima, Esteban Porrini, Esben Iversen, Morten Damgaard, Ove Andersen, Mads Hornum, Trine Meldgaard Lund
BACKGROUND AND HYPOTHESIS: Iohexol and 99mTc-DTPA are commonly used exogenous filtration markers for determining measured glomerular filtration rate (mGFR). Traditional intravenous sampling is time-consuming and often inconvenient in clinical practice, whereas dried blood spot (DBS) sampling is a promising alternative. This study used population pharmacokinetic modeling (popPK) and traditional performance statistics to investigate whether intravenous and DBS sampling can be used interchangeably for measuring GFR in older medical patients with low appetite. METHODS: Older patients aged ≥65 years with poor appetite, defined as a Simplified Nutritional Appetite Questionnaire (SNAQ) score ≤14, received intravenous administration of iohexol and 99mTc-DTPA, followed by sampling over 4-8 hours intravenously (for both tracers) and by DBS (for iohexol). Gentamicin 5 mg/kg was used as a model drug and administered intravenously to all patients, followed by plasma sampling over 22 hours. Employing a previously developed gentamicin popPK model, model fit improvement for each mGFR method was evaluated by reduction in objective function value (OFV) and inter-individual variability (IIV) when including mGFR as a covariate on clearance. Performance of each method relative to intravenous iohexol sampling was also evaluated by bias (median difference) and P15 (percentage of values within 15%). RESULTS: 51 older patients (51% male, aged 67-96) were included. All three mGFR methods improved model fit when implemented as covariates on gentamicin clearance in popPK models (-ΔOFV = 115.6-137.6). The improvements were greater when mGFR was expressed in mL/min, rather than mL/min/1.73 m2. Compared to intravenous sampling of iohexol, DBS sampling of iohexol performed better (bias [95% CI] = 2 [0-3] mL/min, P15 = 98% [94.1%-100%]) than intravenous sampling of 99mTc-DTPA (bias = 4 [3-5] mL/min, P15 = 78.4% [66.7%-88.2%]). CONCLUSIONS: Compared to intravenous sampling of iohexol or 99mTc-DTPA, DBS sampling of iohexol yielded similar improvements to model fit when incorporated as a covariate on gentamicin clearance in a popPK model.