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Published in: Pediatric Nephrology 1/2009

01-01-2009 | Original Article

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

Authors: Malin M. Rhodin, Brian J. Anderson, A. Michael Peters, Malcolm G. Coulthard, Barry Wilkins, Michael Cole, Etienne Chatelut, Anders Grubb, Gareth J. Veal, Michael J. Keir, Nick H. G. Holford

Published in: Pediatric Nephrology | Issue 1/2009

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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.
Footnotes
1
Despite this assumption, one of the authors is a survivor of premature birth in 1946
 
Literature
1.
go back to reference Chen N, Aleksa K, Woodland C, Rieder M, Koren G (2006) Ontogeny of drug elimination by the human kidney. Pediatr Nephrol 21:160–168PubMed Chen N, Aleksa K, Woodland C, Rieder M, Koren G (2006) Ontogeny of drug elimination by the human kidney. Pediatr Nephrol 21:160–168PubMed
2.
go back to reference Sonntag J, Prankel B, Waltz S (1996) Serum creatinine concentration, urinary creatinine excretion and creatinine clearance during the first 9 weeks in preterm infants with a birth weight below 1500 g. Eur J Pediatr 155:815–819PubMed Sonntag J, Prankel B, Waltz S (1996) Serum creatinine concentration, urinary creatinine excretion and creatinine clearance during the first 9 weeks in preterm infants with a birth weight below 1500 g. Eur J Pediatr 155:815–819PubMed
3.
go back to reference Guignard JP, Drukker A (1999) Why do newborn infants have a high plasma creatinine? Pediatrics 103:e49PubMed Guignard JP, Drukker A (1999) Why do newborn infants have a high plasma creatinine? Pediatrics 103:e49PubMed
4.
go back to reference Rubin MI, Bruck E, Rapoport M, Snively M, McKay H, Baumler A (1949) Maturation of renal function in childhood: clearance studies. J Clin Invest 28:1144–1162PubMedPubMedCentral Rubin MI, Bruck E, Rapoport M, Snively M, McKay H, Baumler A (1949) Maturation of renal function in childhood: clearance studies. J Clin Invest 28:1144–1162PubMedPubMedCentral
5.
go back to reference Wilkins BH (1992) Renal function in sick very low birthweight infants: 1. Glomerular filtration rate. Arch Dis Child 67:1140–1145PubMedPubMedCentral Wilkins BH (1992) Renal function in sick very low birthweight infants: 1. Glomerular filtration rate. Arch Dis Child 67:1140–1145PubMedPubMedCentral
6.
go back to reference Swinkels DW, Hendriks JC, Nauta J, de Jong MC (2000) Glomerular filtration rate by single-injection inulin clearance: definition of a workable protocol for children. Ann Clin Biochem 37:60–66PubMed Swinkels DW, Hendriks JC, Nauta J, de Jong MC (2000) Glomerular filtration rate by single-injection inulin clearance: definition of a workable protocol for children. Ann Clin Biochem 37:60–66PubMed
7.
go back to reference Cole M, Price L, Parry A, Keir MJ, Pearson AD, Boddy AV, Veal GJ (2004) Estimation of glomerular filtration rate in paediatric cancer patients using 51CR-EDTA population pharmacokinetics. Br J Cancer 90:60–64PubMedPubMedCentral Cole M, Price L, Parry A, Keir MJ, Pearson AD, Boddy AV, Veal GJ (2004) Estimation of glomerular filtration rate in paediatric cancer patients using 51CR-EDTA population pharmacokinetics. Br J Cancer 90:60–64PubMedPubMedCentral
8.
go back to reference Bird NJ, Henderson BL, Lui D, Ballinger JR, Peters AM (2003) Indexing glomerular filtration rate to suit children. J Nucl Med 44:1037–1043PubMed Bird NJ, Henderson BL, Lui D, Ballinger JR, Peters AM (2003) Indexing glomerular filtration rate to suit children. J Nucl Med 44:1037–1043PubMed
9.
go back to reference Coulthard MG (1985) Maturation of glomerular filtration in preterm and mature babies. Early Hum Dev 11:281–292PubMed Coulthard MG (1985) Maturation of glomerular filtration in preterm and mature babies. Early Hum Dev 11:281–292PubMed
10.
go back to reference Coulthard MG, Hey EN, Ruddock V (1985) Creatinine and urea clearances compared to inulin clearance in preterm and mature babies. Early Hum Dev 11:11–19PubMed Coulthard MG, Hey EN, Ruddock V (1985) Creatinine and urea clearances compared to inulin clearance in preterm and mature babies. Early Hum Dev 11:11–19PubMed
11.
go back to reference Bouvet Y, Bouissou F, Coulais Y, Seronie-Vivien S, Tafani M, Decramer S, Chatelut E (2006) GFR is better estimated by considering both serum cystatin C and creatinine levels. Pediatr Nephrol 21:1299–1306PubMed Bouvet Y, Bouissou F, Coulais Y, Seronie-Vivien S, Tafani M, Decramer S, Chatelut E (2006) GFR is better estimated by considering both serum cystatin C and creatinine levels. Pediatr Nephrol 21:1299–1306PubMed
12.
go back to reference 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 51:1420–1431PubMed 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 51:1420–1431PubMed
13.
go back to reference Beal SL, Sheiner LB, Boeckmann A (1999) NONMEM user’s guide. Division of Pharmacology, University of California, San Francisco Beal SL, Sheiner LB, Boeckmann A (1999) NONMEM user’s guide. Division of Pharmacology, University of California, San Francisco
14.
go back to reference 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 48–53 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 48–53
15.
go back to reference Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B (2005) Quantification of lean bodyweight. Clin Pharmacokinet 44:1051–1065PubMed Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B (2005) Quantification of lean bodyweight. Clin Pharmacokinet 44:1051–1065PubMed
16.
go back to reference Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CM (2004) A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet 43:1167–1178PubMed Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CM (2004) A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet 43:1167–1178PubMed
17.
go back to reference Boyd E (1935) The growth of the surface area of the human body. University of Minnesota Press, Minneapolis Boyd E (1935) The growth of the surface area of the human body. University of Minnesota Press, Minneapolis
18.
go back to reference Sharkey I, Boddy AV, Wallace H, Mycroft J, Hollis R, Picton S (2001) Body surface area estimation in children using weight alone: application in paediatric oncology. Br J Cancer 85:23–28PubMedPubMedCentral Sharkey I, Boddy AV, Wallace H, Mycroft J, Hollis R, Picton S (2001) Body surface area estimation in children using weight alone: application in paediatric oncology. Br J Cancer 85:23–28PubMedPubMedCentral
19.
go back to reference Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 14:4–7 Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 14:4–7
20.
go back to reference Anderson BJ, Holford NH (2008) Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol 48:303–332PubMed Anderson BJ, Holford NH (2008) Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol 48:303–332PubMed
21.
go back to reference Anderson BJ, Allegaert K, Van den Anker JN, Cossey V, Holford NH (2007) Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. Br J Clin Pharmacol 63:75–84PubMed Anderson BJ, Allegaert K, Van den Anker JN, Cossey V, Holford NH (2007) Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. Br J Clin Pharmacol 63:75–84PubMed
22.
go back to reference Richards FJ (1959) A flexible growth function for empirical use. J Exp Bot 10:290–300 Richards FJ (1959) A flexible growth function for empirical use. J Exp Bot 10:290–300
23.
go back to reference Wahlby U, Jonsson EN, Karlsson MO (2001) Assessment of actual significance levels for covariate effects in NONMEM. J Pharmacokinet Pharmacodyn 28:231–252PubMed Wahlby U, Jonsson EN, Karlsson MO (2001) Assessment of actual significance levels for covariate effects in NONMEM. J Pharmacokinet Pharmacodyn 28:231–252PubMed
24.
go back to reference Wahlby U, Bouw MR, Jonsson EN, Karlsson MO (2002) Assessment of type I error rates for the statistical sub-model in NONMEM. J Pharmacokinet Pharmacodyn 29:251–269PubMed Wahlby U, Bouw MR, Jonsson EN, Karlsson MO (2002) Assessment of type I error rates for the statistical sub-model in NONMEM. J Pharmacokinet Pharmacodyn 29:251–269PubMed
25.
go back to reference Parke J, Holford NH, Charles BG (1999) A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models. Comput Methods Programs Biomed 59:19–29PubMed Parke J, Holford NH, Charles BG (1999) A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models. Comput Methods Programs Biomed 59:19–29PubMed
26.
go back to reference Al-Dahhan J, Haycock GB, Chantler C, Stimmler L (1983) Sodium homeostasis in term and preterm neonates. I. Renal aspects. Arch Dis Child 58:335–342PubMedPubMedCentral Al-Dahhan J, Haycock GB, Chantler C, Stimmler L (1983) Sodium homeostasis in term and preterm neonates. I. Renal aspects. Arch Dis Child 58:335–342PubMedPubMedCentral
27.
go back to reference James A, Koren G, Milliken J, Soldin S, Prober C (1987) Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrob Agents Chemother 31:52–54PubMedPubMedCentral James A, Koren G, Milliken J, Soldin S, Prober C (1987) Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrob Agents Chemother 31:52–54PubMedPubMedCentral
28.
go back to reference van der Heijden AJ, Grose WF, Ambagtsheer JJ, Provoost AP, Wolff ED, Sauer PJ (1988) Glomerular filtration rate in the preterm infant: the relation to gestational and postnatal age. Eur J Pediatr 148:24–28PubMed van der Heijden AJ, Grose WF, Ambagtsheer JJ, Provoost AP, Wolff ED, Sauer PJ (1988) Glomerular filtration rate in the preterm infant: the relation to gestational and postnatal age. Eur J Pediatr 148:24–28PubMed
29.
go back to reference Aperia A, Broberger O, Elinder G, Herin P, Zetterstrom R (1981) Postnatal development of renal function in pre-term and full-term infants. Acta Paediatr Scand 70:183–187PubMed Aperia A, Broberger O, Elinder G, Herin P, Zetterstrom R (1981) Postnatal development of renal function in pre-term and full-term infants. Acta Paediatr Scand 70:183–187PubMed
30.
go back to reference Cuzzolin L, Fanos V, Pinna B, di Marzio M, Perin M, Tramontozzi P, Tonetto P, Cataldi L (2006) Postnatal renal function in preterm newborns: a role of diseases, drugs and therapeutic interventions. Pediatr Nephrol 21:931–938PubMed Cuzzolin L, Fanos V, Pinna B, di Marzio M, Perin M, Tramontozzi P, Tonetto P, Cataldi L (2006) Postnatal renal function in preterm newborns: a role of diseases, drugs and therapeutic interventions. Pediatr Nephrol 21:931–938PubMed
31.
go back to reference Holford NHG (1996) A size standard for pharmacokinetics. Clin Pharmacokinet 30:329–332PubMed Holford NHG (1996) A size standard for pharmacokinetics. Clin Pharmacokinet 30:329–332PubMed
32.
go back to reference West GB, Brown JH (2005) The origin of allometric scaling laws in biology from genomes to ecosystems: towards a quantitative unifying theory of biological structure and organization. J Exp Biol 208:1575–1592PubMed West GB, Brown JH (2005) The origin of allometric scaling laws in biology from genomes to ecosystems: towards a quantitative unifying theory of biological structure and organization. J Exp Biol 208:1575–1592PubMed
33.
go back to reference van den Anker JN, de Groot R, Broerse HM, Sauer PJ, van der Heijden BJ, Hop WC, Lindemans J (1995) Assessment of glomerular filtration rate in preterm infants by serum creatinine: comparison with inulin clearance. Pediatrics 96:1156–1158PubMed van den Anker JN, de Groot R, Broerse HM, Sauer PJ, van der Heijden BJ, Hop WC, Lindemans J (1995) Assessment of glomerular filtration rate in preterm infants by serum creatinine: comparison with inulin clearance. Pediatrics 96:1156–1158PubMed
34.
go back to reference Coulthard MG, Hey EN (1984) Weight as the best standard for glomerular filtration in the newborn. Arch Dis Child 59:373–375PubMedPubMedCentral Coulthard MG, Hey EN (1984) Weight as the best standard for glomerular filtration in the newborn. Arch Dis Child 59:373–375PubMedPubMedCentral
35.
go back to reference Dewey FE, Rosenthal D, Murphy DJ Jr, Froelicher VF, Ashley EA (2008) Does size matter? Clinical applications of scaling cardiac size and function for body size. Circulation 117:2279–2287PubMed Dewey FE, Rosenthal D, Murphy DJ Jr, Froelicher VF, Ashley EA (2008) Does size matter? Clinical applications of scaling cardiac size and function for body size. Circulation 117:2279–2287PubMed
36.
go back to reference Hayton WL (2000) Maturation and growth of renal function: dosing renally cleared drugs in children. AAPS PharmSci 2:E3PubMed Hayton WL (2000) Maturation and growth of renal function: dosing renally cleared drugs in children. AAPS PharmSci 2:E3PubMed
37.
go back to reference Calder WA, Braun EJ (1983) Scaling of osmotic regulation in mammals and birds. Am J Physiol 244:R601–R606PubMed Calder WA, Braun EJ (1983) Scaling of osmotic regulation in mammals and birds. Am J Physiol 244:R601–R606PubMed
38.
go back to reference 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 220:1–40 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 220:1–40
39.
go back to reference Singer MA, Morton AR (2000) Mouse to elephant: biological scaling and Kt/V. Am J Kidney Dis 35:306–309PubMed Singer MA, Morton AR (2000) Mouse to elephant: biological scaling and Kt/V. Am J Kidney Dis 35:306–309PubMed
40.
go back to reference Singer MA (2001) Of mice and men and elephants: metabolic rate sets glomerular filtration rate. Am J Kidney Dis 37:164–178PubMed Singer MA (2001) Of mice and men and elephants: metabolic rate sets glomerular filtration rate. Am J Kidney Dis 37:164–178PubMed
41.
go back to reference Edwards NA (1975) Scaling of renal functions in mammals. Comp Biochem Physiol A 52:63–66PubMed Edwards NA (1975) Scaling of renal functions in mammals. Comp Biochem Physiol A 52:63–66PubMed
42.
go back to reference Savage VM, Gillooly JF, Woodruff WH, West GB, Allen AP, Enquist BJ, Brown JH (2004) The predominance of quarter-power scaling in biology. Funct Ecol 18:257–282 Savage VM, Gillooly JF, Woodruff WH, West GB, Allen AP, Enquist BJ, Brown JH (2004) The predominance of quarter-power scaling in biology. Funct Ecol 18:257–282
43.
go back to reference Poole SG, Dooley MJ, Rischin D (2002) A comparison of bedside renal function estimates and measured glomerular filtration rate (Tc99mDTPA clearance) in cancer patients. Ann Oncol 13:949–955PubMed Poole SG, Dooley MJ, Rischin D (2002) A comparison of bedside renal function estimates and measured glomerular filtration rate (Tc99mDTPA clearance) in cancer patients. Ann Oncol 13:949–955PubMed
44.
go back to reference Dooley MJ, Poole SG (2000) Poor correlation between body surface area and glomerular filtration rate. Cancer Chemother Pharmacol 46:523–526PubMed Dooley MJ, Poole SG (2000) Poor correlation between body surface area and glomerular filtration rate. Cancer Chemother Pharmacol 46:523–526PubMed
45.
go back to reference Peters AM, Gordon I, Sixt R (1994) Normalization of glomerular filtration rate in children: body surface area, body weight or extracellular fluid volume? J Nucl Med 35:438–444PubMed Peters AM, Gordon I, Sixt R (1994) Normalization of glomerular filtration rate in children: body surface area, body weight or extracellular fluid volume? J Nucl Med 35:438–444PubMed
46.
go back to reference Leger F, Bouissou F, Coulais Y, Tafani M, Chatelut E (2002) Estimation of glomerular filtration rate in children. Pediatr Nephrol 17:903–907PubMed Leger F, Bouissou F, Coulais Y, Tafani M, Chatelut E (2002) Estimation of glomerular filtration rate in children. Pediatr Nephrol 17:903–907PubMed
47.
go back to reference Stevens LA, Coresh J, Greene T, Levey AS (2006) Assessing kidney function–measured and estimated glomerular filtration rate. N Engl J Med 354:2473–2483PubMed Stevens LA, Coresh J, Greene T, Levey AS (2006) Assessing kidney function–measured and estimated glomerular filtration rate. N Engl J Med 354:2473–2483PubMed
48.
go back to reference Engle WA (2004) Age terminology during the perinatal period. Pediatrics 114:1362–1364PubMed Engle WA (2004) Age terminology during the perinatal period. Pediatrics 114:1362–1364PubMed
49.
go back to reference Tod M, Lokiec F, Bidault R, De Bony F, Petitjean O, Aujard Y (2001) Pharmacokinetics of oral acyclovir in neonates and in infants: a population analysis. Antimicrob Agents Chemother 45:150–157PubMedPubMedCentral Tod M, Lokiec F, Bidault R, De Bony F, Petitjean O, Aujard Y (2001) Pharmacokinetics of oral acyclovir in neonates and in infants: a population analysis. Antimicrob Agents Chemother 45:150–157PubMedPubMedCentral
50.
go back to reference Arant BS Jr (1978) Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr 92:705–712PubMed Arant BS Jr (1978) Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr 92:705–712PubMed
51.
go back to reference Schwartz JB (2003) The influence of sex on pharmacokinetics. Clin Pharmacokinet 42:107–121PubMed Schwartz JB (2003) The influence of sex on pharmacokinetics. Clin Pharmacokinet 42:107–121PubMed
52.
go back to reference Matthews I, Kirkpatrick C, Holford N (2004) Quantitative justification for target concentration intervention–parameter variability and predictive performance using population pharmacokinetic models for aminoglycosides. Br J Clin Pharmacol 58:8–19PubMedPubMedCentral Matthews I, Kirkpatrick C, Holford N (2004) Quantitative justification for target concentration intervention–parameter variability and predictive performance using population pharmacokinetic models for aminoglycosides. Br J Clin Pharmacol 58:8–19PubMedPubMedCentral
53.
go back to reference Martini S, Prevot A, Mosig D, Werner D, van Melle G, Guignard JP (2003) Glomerular filtration rate: measure creatinine and height rather than cystatin C! Acta Paediatr 92:1052–1057PubMed Martini S, Prevot A, Mosig D, Werner D, van Melle G, Guignard JP (2003) Glomerular filtration rate: measure creatinine and height rather than cystatin C! Acta Paediatr 92:1052–1057PubMed
54.
go back to reference Heilbron DC, Holliday MA, al-Dahwi A, Kogan BA (1991) Expressing glomerular filtration rate in children. Pediatr Nephrol 5:5–11PubMed Heilbron DC, Holliday MA, al-Dahwi A, Kogan BA (1991) Expressing glomerular filtration rate in children. Pediatr Nephrol 5:5–11PubMed
55.
go back to reference Han PY, Duffull SB, Kirkpatrick CM, Green B (2007) Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther 82:505–508PubMed Han PY, Duffull SB, Kirkpatrick CM, Green B (2007) Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther 82:505–508PubMed
56.
go back to reference 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 17:863–871 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 17:863–871
Metadata
Title
Human renal function maturation: a quantitative description using weight and postmenstrual age
Authors
Malin M. Rhodin
Brian J. Anderson
A. Michael Peters
Malcolm G. Coulthard
Barry Wilkins
Michael Cole
Etienne Chatelut
Anders Grubb
Gareth J. Veal
Michael J. Keir
Nick H. G. Holford
Publication date
01-01-2009
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 1/2009
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-008-0997-5

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