Skip to main content
SpringerLink
Log in

Derivation of new equations to estimate glomerular filtration rate in pediatric oncology patients

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

Abstract

Background and objective

Monitoring renal function is critical in treating pediatric patients, especially when dosing nephrotoxic agents. We evaluated the validity of the bedside Schwartz and Brandt equations in pediatric oncology patients and developed new equations for estimated glomerular filtration rate (eGFR) in these patients.

Methods

A retrospective analysis was conducted comparing eGFR using the bedside Schwartz and Brandt equations to measured GFR (mGFR) from technetium-99m diethylenetriamine pentaacetic acid (99mTc-DTPA) between January 2007 and August 2013. An improved equation to estimate GFR was developed, simplified, and externally validated in a cohort of patients studied from September 2013 to June 2015. Carboplatin doses calculated from 99mTc-DTPA were compared with doses calculated by GFR-estimating equations.

Results

Overall, the bedside Schwartz and Brandt equations did not precisely or accurately predict measured GFR (mGFR). Using a data subset, we developed a five-covariate equation, which included height, serum creatinine, age, blood urea nitrogen (BUN), and gender, and a simplified version (two-covariates), which contained height and serum creatinine. These equations were used to estimate GFR in 2036 studies, resulting in precise and accurate predictors of mGFR values. Equations were validated in an external cohort of 570 studies; both new equations were more accurate in calculating carboplatin doses than either the bedside Schwartz or Brandt equation.

Conclusions

Two new equations were developed to estimate GFR in pediatric oncology patients, both of which did a better job at estimating mGFR than published equations.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, Hostetter T, Levey AS, Panteghini M, Welch M, Eckfeldt JH, Group NKDEPLW (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 

  2. Lin J, Knight EL, Hogan ML, Singh AK (2003) A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease. J Am Soc Nephrol 14:2573–2580

    Article  PubMed  Google Scholar 

  3. Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K (2012) Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med 156:785–795

    Article  PubMed  Google Scholar 

  4. Schwartz GJ, Muñoz 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 

  5. Staples A, LeBlond R, Watkins S, Wong C, Brandt J (2010) Validation of the revised Schwartz estimating equation in a predominantly non-CKD population. Pediatr Nephrol 25:2321–2326

    Article  PubMed  Google Scholar 

  6. Alford EL, Chhim RF, Crill CM, Hastings MC, Ault BH, Shelton CM (2014) Glomerular filtration rate equations do not accurately predict vancomycin trough concentrations in pediatric patients. Ann Pharmacother 48:691–696

    Article  CAS  PubMed  Google Scholar 

  7. Gibson P, Shammas A, Cada M, Licht C, Gupta AA (2013) The role of Tc-99m-DTPA nuclear medicine GFR studies in pediatric solid tumor patients. J Pediatr Hematol Oncol 35:108–111

    Article  PubMed  Google Scholar 

  8. Brandt JR, Wong C, Jones DR, Qualls C, McAfee N, Brewer E, Watkins SL (2003) Glomerular filtration rate in children with solid tumors: normative values and a new method for estimation. Pediatr Hematol Oncol 20:309–318

    Article  CAS  PubMed  Google Scholar 

  9. Brandt JR, Wong CS, Hanrahan JD, Qualls C, McAfee N, Watkins SL (2006) Estimating absolute glomerular filtration rate in children. Pediatr Nephrol 21:1865–1872

    Article  PubMed  Google Scholar 

  10. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J, Eknoyan G, Foundation NK (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139:137–147

    Article  PubMed  Google Scholar 

  11. Rodman JH, Maneval DC, Magill HL, Sunderland M (1993) Measurement of Tc-99m DTPA serum clearance for estimating glomerular filtration rate in children with cancer. Pharmacotherapy 13:10–16

    CAS  PubMed  Google Scholar 

  12. 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 90:60–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Marina NM, Rodman JH, Shema SJ, Bowman LC, Douglass E, Furman W, Santana VM, Hudson M, Wilimas J, Meyer W, Madden T, Pratt CB (1993) Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors. J Clinl Oncol 11:554–560

    Article  CAS  Google Scholar 

  14. Murry DJ, Sandlund JT, Stricklin LM, Rodman JH (1993) Pharmacokinetics and acute renal effects of continuously infused carboplatin. Clin Pharmacol Ther 54:374–380

    Article  CAS  PubMed  Google Scholar 

  15. Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce RD, Zhang YL, Greene T, Levey AS (2008) Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 51:395–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cohen J (1988) Statistical power analysis for the behavioral sciences. Routledge Academic, New York

    Google Scholar 

  17. Cathomas R, Klingbiel D, Geldart TR, Mead GM, Ellis S, Wheater M, Simmonds P, Nagaraj N, von Moos R, Fehr M (2014) Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort. Ann Oncol 25:1591–1597

    Article  CAS  PubMed  Google Scholar 

  18. Bernhardt MB, Moffett BS, Johnson M, Tam VH, Thompson P, Garey KW (2015) Agreement among measurements and estimations of glomerular filtration in children with cancer. Pediatr Blood Cancer 62:80–84

    Article  PubMed  Google Scholar 

  19. Blufpand HN, Tromp J, Abbink FC, Stoffel-Wagner B, Bouman AA, Schouten-van Meeteren AY, van Wijk JA, Kaspers GJ, Bökenkamp A (2011) Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy. Pediatr Blood Cancer 57:262–267

    Article  PubMed  Google Scholar 

  20. Andersen TB, Jødal L, Erlandsen EJ, Morsing A, Frøkiær J, Brøchner-Mortensen J (2013) Detecting reduced renal function in children: comparison of GFR-models and serum markers. Pediatr Nephrol 28:83–92

    Article  PubMed  Google Scholar 

  21. 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 

Download references

Acknowledgements

This work was supported by the National Cancer Institute [Grants CA154619, CA21765] and the American Lebanese Syrian Associated Charities at St. Jude Children’s Research Hospital. The authors acknowledge Dr. Dennis Jay for his helpful comments in the preparation and review of the manuscript.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA

    Vanessa E. Millisor, Jessica K. Roberts, Vinay M. Daryani, Alejandro Molinelli & Clinton F. Stewart

  2. Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Yilun Sun & Li Tang

  3. Department of Pharmaceutical Services, St. Jude Children’s Research Hospital, Memphis, TN, USA

    David Gregornik, Shane J. Cross, Deborah Ward & Jennifer L. Pauley

  4. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Rachel C. Brennan

Authors
  1. Vanessa E. Millisor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jessica K. Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yilun Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vinay M. Daryani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David Gregornik
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shane J. Cross
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Deborah Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jennifer L. Pauley
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alejandro Molinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Rachel C. Brennan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Clinton F. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clinton F. Stewart.

Ethics declarations

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Disclosure of potential conflicts of interest

The authors have nothing to declare.

Additional information

Vanessa E. Millisor and Jessica K. Roberts are Co-first Authors

Electronic supplementary material

Online Resource 1

Linear relationship between the ratio of height to serum creatinine and measured glomerular filtration rate (GFR) (n = 2036). The solid line is the best-fit line through the data, and the dotted line is the line of identity. (PDF 191 kb)

Online Resource 2

Bland-Altman plot for the simplified equation using the validation data set (n = 570). The solid line represents the mean of the difference, and dashed lines represent ±2 standard deviations. (PDF 251 kb)

Online Resource 3

Supplemental Table 1. Comparison of carboplatin dose based on estimated and measured glomerular filtration rate (GFR) for each estimating equation (Bedside Schwartz, Brandt, five-covariate, simplified) evaluated in derivation and validation cohorts. (DOCX 140 kb)

Online Resource 4

Supplemental Table 2. Bias and accuracy results for the bedside Schwartz, Brandt, five-covariate, and simplified equations when analyzed by primary diagnosis (e.g., hematological diagnosis, brain tumors, solid tumors). Results were similar for all three types of malignancy—the five-covariate equation had the best performance in estimating glomerular filtration rate (GFR), followed by the simplified equation, Brandt equation, and then bedside Schwartz equation. Findings were also analyzed using the external validation cohort (index cases = 1007). (DOCX 162 kb)

Online Resource 5

Supplemental Table 3. Overall and group -specific bias and accuracy results for the bedside Schwartz, Brandt, five-covariate, and simplified equations when analyzed on index cases (n = 1044) and respective subgroups. (DOCX 53 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Millisor, V.E., Roberts, J.K., Sun, Y. et al. Derivation of new equations to estimate glomerular filtration rate in pediatric oncology patients. Pediatr Nephrol 32, 1575–1584 (2017). https://doi.org/10.1007/s00467-017-3693-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-017-3693-5

Keywords

Search

Navigation