Skip to main content
SpringerLink
Log in

Normalization of glomerular filtration rate in obese children

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA), but this may lead to biased results when applied to subjects of abnormal body size. The aim of our study was to examine the impact of normalization to the BSA and alternative body size descriptors on measured and estimated GFR in overweight and obese children.

Methods

This was a cross-sectional study of 313 children aged 8–9 years old. GFR was measured by 24-h creatinine clearance (CrCl) and additionally estimated from serum creatinine and cystatin C (CysC) using the combined Zappitelli formula, both as absolute values and adjusted to various body size descriptors. The results were compared between 163 normal-weight, 89 overweight and 61 obese children.

Results

Compared to the normal-weight children, mean absolute GFR (both measured and estimated) was higher in the overweight and obese children, whereas BSA-adjusted GFR was lower. Linear regression models fitted in normal-weight children revealed equally close associations between absolute GFR and squared height, ideal body weight (IBW) and BSA derived from IBW. Normalization of GFR to the IBW-derived BSA completely eliminated the discrepancy between absolute and BSA-indexed GFR in overweight and obese children.

Conclusions

Indexing of GFR to BSA calculated from the ideal—rather than actual—body weight is a promising approach to avoid overcorrection when studying obese children. Further studies should assess the accuracy of this approach across the full range of age and BMI distribution.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Savino A, Pelliccia P, Chiarelli F, Mohn A (2010) Obesity-related renal injury in childhood. Horm Res Paediatr 73:303–311

    Article  CAS  PubMed  Google Scholar 

  2. Levey AS, Kramer H (2010) Obesity, glomerular hyperfiltration, and the surface area correction. Am J Kidney Dis 56:255–258

    Article  PubMed  Google Scholar 

  3. McIntosh JF, Möller E, Van Slyke DD (1928) Studies of urea excretion. III: The influence of body size on urea output. J Clin Invest 6:467–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Delanaye P, Mariat C, Cavalier E, Krzesinski J-M (2009) Errors induced by indexing glomerular filtration rate for body surface area: reductio ad absurdum. Nephrol Dial Transpl 24:3593–3596

    Article  Google Scholar 

  5. Heaf JG (2007) The origin of the 1 x 73-m2 body surface area normalization: problems and implications. Clin Physiol Funct Imaging 27:135–137

    Article  PubMed  Google Scholar 

  6. Hallynck TH, Soep HH, Thomis JA, Boelaert J, Daneels R, Dettli L (1981) Should clearance be normalised to body surface or to lean body mass? Br J Clin Pharmacol 11:523–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Delanaye P, Krzesinski J-M (2011) Indexing of renal function parameters by body surface area: intelligence or folly? Nephron Clin Pract 119:c289–292

    Article  PubMed  Google Scholar 

  8. Ruggieri G, Rocca AR (2010) Analysis of past and present methods of measuring and estimating body surface area and the resulting evaluation of its doubtful suitability to universal application. Blood Purif 30:296–305

    Article  PubMed  Google Scholar 

  9. Wuerzner G, Bochud M, Giusti V, Burnier M (2011) Measurement of glomerular filtration rate in obese patients: pitfalls and potential consequences on drug therapy. Obes Facts 4:238–243

    Article  PubMed  Google Scholar 

  10. Soares AA, Prates AB, Weinert LS, Veronese FV, de Azevedo MJ, Silveiro SP (2013) Reference values for glomerular filtration rate in healthy Brazilian adults. BMC Nephrol 14:54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Peters AM, Perry L, Hooker CA, Howard B, Neilly MDJ, Seshadri N, Sobnack R, Irwin A, Snelling H, Gruning T, Patel NH, Lawson RS, Shabo G, Williams N, Dave S, Barnfield MC (2012) Extracellular fluid volume and glomerular filtration rate in 1878 healthy potential renal transplant donors: effects of age, gender, obesity and scaling. Nephrol Dial Transpl 27:1429–1437

    Article  CAS  Google Scholar 

  12. Si H, Lei Z, Li S, Liu J, Geng J, Chen S (2013) Lean body mass is better than body surface area in correcting GFR. Clin Nucl Med 38:e210–215

    Article  PubMed  Google Scholar 

  13. Redal-Baigorri B, Rasmussen K, Heaf JG (2013) The use of absolute values improves performance of estimation formulae: a retrospective cross sectional study. BMC Nephrol 14:271

    Article  PubMed  PubMed Central  Google Scholar 

  14. Anastasio P, Spitali L, Frangiosa A, Molino D, Stellato D, Cirillo E, Pollastro RM, Capodicasa L, Sepe J, Federico P, Gaspare De Santo N (2000) Glomerular filtration rate in severely overweight normotensive humans. Am J Kidney Dis 35:1144–1148

    Article  CAS  PubMed  Google Scholar 

  15. Wuerzner G, Pruijm M, Maillard M, Bovet P, Renaud C, Burnier M, Bochud M (2010) Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population. Am J Kidney Dis 56:303–312

    Article  PubMed  Google Scholar 

  16. Janmahasatian S, Duffull SB, Chagnac A, Kirkpatrick CMJ, Green B (2008) Lean body mass normalizes the effect of obesity on renal function. Br J Clin Pharmacol 65:964–965

    Article  PubMed  PubMed Central  Google Scholar 

  17. Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CMJ (2004) A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet 43:1167–1178

    Article  PubMed  Google Scholar 

  18. Eriksen BO, Melsom T, Mathisen UD, Jenssen TG, Solbu MD, Toft I (2011) GFR normalized to total body water allows comparisons across genders and body sizes. J Am Soc Nephrol 22:1517–1525

    Article  PubMed  PubMed Central  Google Scholar 

  19. Delanaye P, Radermecker RP, Rorive M, Depas G, Krzesinski JM (2005) Indexing glomerular filtration rate for body surface area in obese patients is misleading: concept and example. Nephrol Dial Transpl 20:2024–2028

    Article  Google Scholar 

  20. Peters AM, Glass DM (2010) Use of body surface area for assessing extracellular fluid volume and glomerular filtration rate in obesity. Am J Nephrol 31:209–213

    Article  PubMed  Google Scholar 

  21. Bird NJ, Henderson BL, Lui D, Ballinger JR, Peters AM (2003) Indexing glomerular filtration rate to suit children. J Nucl Med 44:1037–1043

    PubMed  Google Scholar 

  22. Larsen PS, Kamper-Jorgensen M, Adamson A, Barros H, Bonde JP, Brescianini S, Brophy S, Casas M, Charles M-AA, Devereux G, Eggesbo M, Fantini MP, Frey U, Gehring U, Grazuleviciene R, Henriksen TB, Hertz-Picciotto I, Heude B, Hryhorczuk DO, Inskip H, Jaddoe VWV, Lawlor DA, Ludvigsson J, Kelleher C, Kiess W, Koletzko B, Kuehni CE, Kull I, Kyhl HB, Magnus P, Momas I, Murray D, Pekkanen J, Polanska K, Porta D, Poulsen G, Richiardi L, Roeleveld N, Skovgaard AM, Sram RJ, Strandberg-Larsen K, Thijs C, Van Eijsden M, Wright J, Vrijheid M, Andersen A-MNM, Kamper-Jørgensen M, Adamson A, Barros H, Bonde JP, Brescianini S, Brophy S, Casas M, Charles M-AA, Devereux G, Eggesbø M, Fantini MP, Frey U, Gehring U, Grazuleviciene R, Henriksen TB, Hertz-Picciotto I, Heude B, Hryhorczuk DO, Inskip H, Jaddoe VWV, Lawlor DA, Ludvigsson J, Kelleher C, Kiess W, Koletzko B, Kuehni CE, Kull I, Kyhl HB, Magnus P, Momas I, Murray D, Pekkanen J, Polanska K, Porta D, Poulsen G, Richiardi L, Roeleveld N, Skovgaard AM, Sram RJ, Strandberg-Larsen K, Thijs C, Van Eijsden M, Wright J, Vrijheid M, Andersen A-MNM (2013) Pregnancy and birth cohort resources in europe: a large opportunity for aetiological child health research. Paediatr Perinat Epidemiol 27:393–414

    Article  PubMed  Google Scholar 

  23. Durão C, Severo M, Oliveira A, Moreira P, Guerra A, Barros H, Lopes C, Durao C, Severo M, Oliveira A, Moreira P, Guerra A, Barros H, Lopes C (2014) Evaluating the effect of energy-dense foods consumption on preschool children’s body mass index: a prospective analysis from 2 to 4 years of age. Eur J Nutr 54:835–843

    Article  PubMed  Google Scholar 

  24. de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J (2007) Development of a WHO growth reference for school-aged children and adolescents. Bull World Heal Organ 85:660–667

    Article  Google Scholar 

  25. Fenton TR, Kim JH (2013) A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 13:59

    Article  PubMed  PubMed Central  Google Scholar 

  26. Peters AM, Snelling HLR, Glass DM, Bird NJ (2011) Estimation of lean body mass in children. Br J Anaesth 106:719–723

    Article  CAS  PubMed  Google Scholar 

  27. Schaefer F, Georgi M, Zieger A, Schärer K (1994) Usefulness of bioelectric impedance and skinfold measurements in predicting fat-free mass derived from total body potassium in children. Pediatr Res 35:617–624

    Article  CAS  PubMed  Google Scholar 

  28. Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height–weight formula validated in infants, children, and adults. J Pediatr 93:62–66

    Article  CAS  PubMed  Google Scholar 

  29. Ross EL, Jorgensen J, DeWitt PE, Okada C, Porter R, Haemer M, Reiter PD (2014) Comparison of 3 body size descriptors in critically ill obese children and adolescents: implications for medication dosing. J Pediatr Pharmacol Ther 19:103–110

    PubMed  PubMed Central  Google Scholar 

  30. Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, Hostetter T, Levey AS, Panteghini M, Welch M, Eckfeldt JH (2006) Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem 52:5–18

    Article  CAS  PubMed  Google Scholar 

  31. Grubb A, Blirup-Jensen S, Lindström V, Schmidt C, Althaus H, Zegers I (2010) First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clin Chem Lab Med 48:1619–1621

    Article  CAS  PubMed  Google Scholar 

  32. Zappitelli M, Parvex P, Joseph L, Paradis G, Grey V, Lau S, Bell L (2006) Derivation and validation of cystatin C-based prediction equations for GFR in children. Am J Kidney Dis 48:221–230

    Article  CAS  PubMed  Google Scholar 

  33. Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    Article  PubMed  PubMed Central  Google Scholar 

  34. Remer T, Neubert A, Maser-Gluth C (2002) Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research. Am J Clin Nutr 75:561–569

    CAS  PubMed  Google Scholar 

  35. Tomaszewski M, Charchar FJ, Maric C, McClure J, Crawford L, Grzeszczak W, Sattar N, Zukowska-Szczechowska E, Dominiczak AF (2007) Glomerular hyperfiltration: a new marker of metabolic risk. Kidney Int 71:816–821

    Article  CAS  PubMed  Google Scholar 

  36. Chagnac A, Weinstein T, Korzets A, Ramadan E, Hirsch J, Gafter U (2000) Glomerular hemodynamics in severe obesity. Am J Physiol Ren Physiol 278:F817–822

    CAS  Google Scholar 

  37. Naour N, Fellahi S, Renucci J-F, Poitou C, Rouault C, Basdevant A, Dutour A, Alessi M-C, Bastard J-P, Clément K, Guerre-Millo M (2009) Potential contribution of adipose tissue to elevated serum cystatin C in human obesity. Obesity (Silver Spring) 17:2121–2126

    Article  CAS  Google Scholar 

  38. Roos JF, Doust J, Tett SE, Kirkpatrick CMJ (2007) Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children–a meta-analysis. Clin Biochem 40:383–391

    Article  CAS  PubMed  Google Scholar 

  39. Piepsz A, Tondeur M, Ham H (2008) Escaping the correction for body surface area when calculating glomerular filtration rate in children. Eur J Nucl Med Mol Imaging 35:1669–1672

    Article  PubMed  Google Scholar 

  40. Lemoine S, Guebre-Egziabher F, Sens F, Nguyen-Tu M-S, Juillard L, Dubourg L, Hadj-Aissa A (2014) Accuracy of GFR estimation in obese patients. Clin J Am Soc Nephrol 9:720–727

    Article  PubMed  PubMed Central  Google Scholar 

  41. Pai MP, Cojutti P, Pea F (2014) Levofloxacin dosing regimen in severely morbidly obese patients (BMI ≥40 kg/m(2)) should be guided by creatinine clearance estimates based on ideal body weight and optimized by therapeutic drug monitoring. Clin Pharmacokinet 53:753–762

    Article  CAS  PubMed  Google Scholar 

  42. Maskatia SA, Spinner JA, Nutting AC, Slesnick TC, Krishnamurthy R, Morris SA (2013) Impact of obesity on ventricular size and function in children, adolescents and adults with Tetralogy of Fallot after initial repair. Am J Cardiol 112:594–598

    Article  PubMed  Google Scholar 

  43. Schwartz GJ, Work DF (2009) Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol 4:1832–1843

    Article  PubMed  Google Scholar 

  44. Hellerstein S, Berenbom M, Alon US, Warady BA (1998) Creatinine clearance following cimetidine for estimation of glomerular filtration rate. Pediatr Nephrol 12:49–54

    Article  CAS  PubMed  Google Scholar 

  45. Correia-Costa L, Afonso AC, Schaefer F, Guimarães JT, Bustorff M, Guerra A, Barros H, Azevedo A (2015) Decreased renal function in overweight and obese prepubertal children. Pediatr Res 78:436–444

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the families enrolled in Generation XXI for their kindness, all members of the research team for their enthusiasm and perseverance and the participating hospitals and their staff for their help and support.

Author information

Authors and Affiliations

  1. Epidemiology Research Unit (EPIUnit), Institute of Public Health, University of Porto (ISPUP), Rua das Taipas nr. 135, 4050-600, Porto, Portugal

    Liane Correia-Costa, Alberto Caldas Afonso, João Tiago Guimarães, Henrique Barros & Ana Azevedo

  2. Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal

    Liane Correia-Costa & Alberto Caldas Afonso

  3. Department of Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal

    Liane Correia-Costa, Alberto Caldas Afonso & António Guerra

  4. Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany

    Franz Schaefer

  5. Department of Nephrology, Centro Hospitalar São João, Porto, Portugal

    Manuela Bustorff

  6. Department of Clinical Pathology , Centro Hospitalar São João, Porto, Portugal

    João Tiago Guimarães

  7. Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal

    João Tiago Guimarães

  8. Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal

    António Guerra

  9. Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal

    Henrique Barros & Ana Azevedo

Authors
  1. Liane Correia-Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franz Schaefer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alberto Caldas Afonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manuela Bustorff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. João Tiago Guimarães
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. António Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Henrique Barros
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ana Azevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liane Correia-Costa.

Ethics declarations

Conflict of interest

None of the authors have any financial or nonfinancial competing interests concerning the present study.

Sources of funding

This project was supported by FEDER funds from Programa Operacional Factores de Competitividade—COMPETE (FCOMP-01-0124-FEDER-028751)—and by national funds from the Portuguese Foundation for Science and Technology, Lisbon, Portugal (PTDC/DTP-PIC/0239/2012). Liane Correia-Costa was supported by the Portuguese Foundation for Science and Technology (grant SFRH/SINTD/95898/2013) and Franz Schaefer was supported by the ERA-EDTA Research Programme and the KfH Foundation for Preventive Medicine.

Ethics

The ObiKid project was approved by the Ethics Committee of Centro Hospitalar São João, Porto, Portugal, and by the Faculty of Medicine of the University of Porto and complies with the Helsinki Declaration and the current national legislation. Written informed consent from parents (or their legal substitute) and verbal assent from children was obtained.

Additional information

Liane Correia-Costa and Franz Schaefer contributed equally as first authors to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Figure 1

(PDF 165 kb)

Supplementary Figure 2

(PDF 170 kb)

Supplementary Figure 3

(PDF 172 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Correia-Costa, L., Schaefer, F., Afonso, A.C. et al. Normalization of glomerular filtration rate in obese children. Pediatr Nephrol 31, 1321–1328 (2016). https://doi.org/10.1007/s00467-016-3367-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-016-3367-8

Keywords

Search

Navigation