Consistent Methods for Fat Free Mass, Creatinine Production Rate,
Creatinine Clearance and Glomerular Filtration Rate for Description of
Renal Function from Neonates to Adults
Abstract
Aim: Renal function is an important covariate to describe variability in
clearance of renally eliminated drugs. Estimating glomerular filtration
rate (GFR) should account for differences in size, age and body
composition consistently when using GFR to determine drug dosage. We
aimed to develop a continuous model for renal function from prematurity
to adulthood based on models for fat free mass (FFM), creatinine
production rate (CPR) and GFR. Methods: A model for fractional FFM in
premature neonates to adults was developed using pooled data from 4462
subjects and 2847 FFM observations. Data from 108 subjects with
measurements of serum creatinine and GFR were used to construct a model
for CPR by assuming that CLcr is equal to GFR. A previously published
model for human GFR was updated using the model for fractional FFM and
accounting for the effects of maturation and birth. Together these
models were used to predict renal function. Results: Girls have a FFM
larger than that predicted from adult women based on height, weight and
sex. Boys have a FFM lower than adult men predicted FFM until around the
onset of puberty, when it approaches adult values. CPR can be predicted
using FFM, post menstrual age and sex and avoids discontinuous
predictions between neonates, children and adults. The updated model for
GFR maturation was used to describe expected normal GFR. Renal function
calculated from the ratio of individual CLcr to normal GFR. Conclusion:
Continuous models for FFM, CPR and GFR predict renal function
independent of age and size.