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, 51Cr-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.
KeywordsAllometry Fat-free mass Body composition Glomerular filtration rate Lean body weight Postmenstrual age Renal function
Body mass index
Body surface area
Asymmetry parameter for the sigmoid hyperbolic model
Fraction of fat mass
Glomerular filtration rate
An exponent describing the steepness of the sigmoid hyperbolic model (taken from the equation describing the oxygen dissociation curve originally described by Hill in 1910)
Normal fat mass
Computer software for nonlinear mixed effects modelling
The maturation half time, i.e. the time to reach 50% of mature function
Visual predictive check
Support was provided solely from institutional and/or departmental sources.
Ethical approval was not required.
- 12.Grubb A, Nyman U, Bjork J, Lindstrom V, Rippe B, Sterner G, Christensson A (2005) Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan-Barratt prediction equations for children. Clin Chem 51:1420–1431PubMedCrossRefGoogle Scholar
- 13.Beal SL, Sheiner LB, Boeckmann A (1999) NONMEM user’s guide. Division of Pharmacology, University of California, San FranciscoGoogle Scholar
- 14.Peters HP (1983) Chapter 4. Physiological correlates of size. In: Beck E, Birks HJB, Conner EF (eds) The Ecological Implications of Body Size. Cambridge University Press, Cambridge, pp 48–53Google Scholar
- 17.Boyd E (1935) The growth of the surface area of the human body. University of Minnesota Press, MinneapolisGoogle Scholar
- 19.Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 14:4–7Google Scholar
- 38.Brody S, Proctor RC, Ashworth US (1934) Basal metabolism, endogenous nitrogen, creatinine, and sulphur excretions as functions of body weight. Univ Mo Agric Exp Sta Res Bull 220:1–40Google Scholar
- 56.Du Bois D, Du Bois EF (1916) Clinical calorimetry: tenth paper. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 17:863–871Google Scholar