Human renal function maturation: a quantitative description using weight and postmenstrual age.
This study pools published data to describe the increase in glomerular filtration rate (GFR) from very premature neonates to young adults. The data comprises measured GFR (using polyfructose, (51)Cr-EDTA, mannitol or iohexol) from eight studies (n = 923) and involved very premature neonates (22 weeks postmenstrual age) to adulthood (31 years). A nonlinear mixed effects approach (NONMEM) was used to examine the influences of size and maturation on renal function. Size was the primary covariate, and GFR was standardized for a body weight of 70 kg using an allometric power model. Postmenstrual age (PMA) was a better descriptor of maturational changes than postnatal age (PNA). A sigmoid hyperbolic model described the nonlinear relationship between GFR maturation and PMA. Assuming an allometric coefficient of 3/4, the fully mature (adult) GFR is predicted to be 121.2 mL/min per 70 kg [95% confidence interval (CI) 117-125]. Half of the adult value is reached at 47.7 post-menstrual weeks (95%CI 45.1-50.5), with a Hill coefficient of 3.40 (95%CI 3.03-3.80). At 1-year postnatal age, the GFR is predicted to be 90% of the adult GFR. Glomerular filtration rate can be predicted with a consistent relationship from early prematurity to adulthood. We propose that this offers a clinically useful definition of renal function in children and young adults that is independent of the predictable changes associated with age and size.
Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden.
Malin M
MM
Rhodin
Brian J
BJ
Anderson
A Michael
AM
Peters
Malcolm G
MG
Coulthard
Barry
B
Wilkins
Michael
M
Cole
Etienne
E
Chatelut
Anders
A
Grubb
Gareth J
GJ
Veal
Michael J
MJ
Keir
Nick H G
NH
Holford
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D001835:Body Weight / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D005865:Gestational Age; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development*; D007668:Kidney / Q000254:growth & development*; D007677:Kidney Function Tests; D008297:Male; D055815:Young Adult