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Human renal function maturation: a quantitative description using weight and postmenstrual age

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Abstract

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.

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Notes

  1. Despite this assumption, one of the authors is a survivor of premature birth in 1946

Abbreviations

BMI:

Body mass index

BSA:

Body surface area

δ:

Asymmetry parameter for the sigmoid hyperbolic model

Ffat:

Fraction of fat mass

FFM:

Fat-free mass

GFR:

Glomerular filtration rate

Hill:

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)

NFM:

Normal fat mass

NONMEM:

Computer software for nonlinear mixed effects modelling

PMA:

Postmenstrual age

PNA:

Postnatal age

PWR:

Power exponent

TM50 :

The maturation half time, i.e. the time to reach 50% of mature function

VPC:

Visual predictive check

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Authors and Affiliations

  1. Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden

    Malin M. Rhodin

  2. Department of Anesthesiology, University of Auckland, Auckland, New Zealand

    Brian J. Anderson

  3. Department of Applied Physiology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK

    A. Michael Peters

  4. Paediatric Nephrology, Royal Victoria Infirmary, Newcastle, NE1 4LP, UK

    Malcolm G. Coulthard

  5. Paediatric Intensive Care Unit, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia

    Barry Wilkins

  6. Northern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK

    Michael Cole & Gareth J. Veal

  7. EA3035 Université Paul-Sabatier and Institut Claudius-Regaud, 20 rue du Pont-Saint-Pierre, 31052, Toulouse, France

    Etienne Chatelut

  8. Department of Clinical Chemistry, University Hospital, 22185, Lund, Sweden

    Anders Grubb

  9. Department of Medical Physics, Medical School, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK

    Michael J. Keir

  10. Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand

    Nick H. G. Holford

  11. C/-PICU, Auckland Children’s Hospital, Park Road, Auckland, New Zealand

    Brian J. Anderson

Authors
  1. Malin M. Rhodin
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  2. Brian J. Anderson
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  3. A. Michael Peters
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  4. Malcolm G. Coulthard
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  5. Barry Wilkins
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  6. Michael Cole
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  8. Anders Grubb
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  9. Gareth J. Veal
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Correspondence to Brian J. Anderson.

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Rhodin, M.M., Anderson, B.J., Peters, A.M. et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol 24, 67–76 (2009). https://doi.org/10.1007/s00467-008-0997-5

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  • DOI: https://doi.org/10.1007/s00467-008-0997-5

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