Glomerular filtration rate in children and young adults with
haemato-oncological disease and infection is best described by
three-compartmental iohexol model
Abstract
Background. Children with cancer and infection may develop glomerular
hyperfiltration (GH). With the aim to determine the prevalence of GH in
children and young adults with haemato-oncological disease and infection
we developed population pharmacokinetic model of iohexol. We further
aimed to assess the accuracy of estimated glomerular filtration rate
(eGFR) equations and single- or two-point measured GFR (mGFR) formulas
compared with GFR based on iohexol clearance from our population
pharmacokinetic model (iGFR). Procedure. Hospitalized patients (0.5-25
years) with haemato-oncological disease and infection were included if
their eGFR was ≥80 mL/min/1.73 m2 at the screening visit. Iohexol plasma
concentrations were described by population pharmacokinetic model. Bias,
precision and accuracy of 23 eGFR equations and 18 mGFR formulas were
calculated. Results. Total of 32 iohexol administrations was performed
in 28 patients. Median (range) eGFR was 136 (74-234) mL/min/1.73 m2 and
age 15.1 (0.8-26.0) years. Three-compartment model with allometric
scaling of central, one peripheral compartment and clearance (with power
0.75) to weight fitted the best. Median (range) iGFR was 103 (68-140)
mL/min/1.73 m2. All except one eGFR equation overestimated GFR.
Lund-Malmö revised eGFR equation performed the best, followed by Gao
equation. Of single- or two-point mGFR formulas 15 overestimated iGFR.
Modified Jacobsson formula at 5.5 h performed the best, followed by
Fleming formula at 3 h. Conclusions. In children and young adults with
haemato-oncological disease and infection renal function is best
described by iohexol clearance from three-compartmental pharmacokinetic
model, while eGFR equations and single- and two-point mGFR formulas
overestimate iGFR.