Variables of interest to predict glomerular filtration rate in preterm newborns in the first days of life

Abstract

Background

Measurement of neonatal renal function is challenging, and accurate, easy-to-use markers to estimate glomerular filtration rate (eGFR) are lacking. This study aimed to evaluate principal determinants of GFR in neonates and develop a predictive equation.

Methods

GFR was measured, using single injection inulin clearance, at median day 3 of life in 48 newborns. Associations of clearance with height, gestational age, weight, creatinine, and cystatin C were explored and a multivariable model to estimate GFR developed. We also evaluated preexisting GFR equations (Schwartz, Zappitelli, combined Zappitelli).

Results

Forty-four clearances were measured, 36 very preterm neonates (28–32 weeks); 5 extremely preterm (< 28 weeks), and 3 term newborns. No patient presented acute renal insufficiency. Median inulin clearance in preterm infants was 18.83 ml/min/1.73 m2 (IQ 15.29; 24.99). Inulin clearance correlated with weight (ρ 0.74), gestational age (ρ 0.72), height (ρ 0.49), and creatinine (ρ − 0.42), but not cystatin C. In the multivariable model, predicted GFR equation was 2.32* (weight (g))0.64/(creatinine (mcmol/l))0.62. Mean error in predicting clearance was − 0.8 ml/min/1.73 m2 (− 3.0–1.4) ranging from − 14.9 to 13.3 ml/min/1.73 m2. Mean prediction error with Zappitelli and combined Zappitelli equations were 28.5 ml/min/1.73 m2 (95% CI 24.6–32.3) and 28.3 ml/min/1.73 m2 (95% CI 24.9–31.7), respectively, and 2 ml/min/1.73 m2 (95% CI − 0.6–4.6) for Schwartz equation.

Conclusions

Weight and gestational age are crucial determinants of GFR in neonates. The Zappitelli models were not validated in our population. Our predictive model and Schwartz models performed better. Our model should be evaluated in another preterm population, particularly in those presenting renal insufficiency.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Abbreviations

GFR:

Glomerular filtration rate

eGFR:

Estimated glomerular filtration rate

GA:

Gestational age

References

  1. 1.

    Jetton JG, Guillet R, Askenazi DJ, Dill L, Jacobs J, Kent AL, Selewski DT, Abitbol CL, Kaskel FJ, Mhanna MJ, Ambalavanan N, Charlton JR, Collaborative NK (2016) Assessment of worldwide acute kidney injury epidemiology in neonates: design of a retrospective cohort study. Front Pediatr 4:68

    Article  Google Scholar 

  2. 2.

    Askenazi DJ, Ambalavanan N, Goldstein SL (2009) Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Pediatr Nephrol 24:265–274

    Article  Google Scholar 

  3. 3.

    Stritzke A, Thomas S, Amin H, Fusch C, Lodha A (2017) Renal consequences of preterm birth. Mol Cell Pediatr 4:2

    Article  Google Scholar 

  4. 4.

    Abitbol CL, DeFreitas MJ, Strauss J (2016) Assessment of kidney function in preterm infants: lifelong implications. Pediatr Nephrol 31:2213–2222

    Article  Google Scholar 

  5. 5.

    Abitbol CL, Rodriguez MM (2012) The long-term renal and cardiovascular consequences of prematurity. Nat Rev Nephrol 8:265–274

    CAS  Article  Google Scholar 

  6. 6.

    Luyckx VA, Brenner BM (2005) Low birth weight, nephron number, and kidney disease. Kidney Int Suppl 97:S68–S77

    Article  Google Scholar 

  7. 7.

    Filler G (2015) A step forward towards accurately assessing glomerular filtration rate in newborns. Pediatr Nephrol 30:1209–1212

    Article  Google Scholar 

  8. 8.

    Montini G, Cosmo L, Amici G, Mussap M, Zacchello G (2001) Plasma cystatin C values and inulin clearances in premature neonates. Pediatr Nephrol 16:463–465

    CAS  Article  Google Scholar 

  9. 9.

    Van Rossum LK, Mathot RAA, Cransberg K, Vulto AG (2003) Optimal sampling strategies to assess inulin clearance in children by the inulin single-injection method. Clin Chem 49:1170–1179

    Article  Google Scholar 

  10. 10.

    Van Rossum LK, Mathot RAA, Cransberg K, Vulto AG (2003) Optimal sampling strategies to assess inulin clearance in children by the inulin single-injection method. Clin Chem 49:1170–1179

    Article  Google Scholar 

  11. 11.

    Coulthard MG (1983) Comparison of methods of measuring renal function in preterm babies using inulin. J Pediatr 102:923–930

    CAS  Article  Google Scholar 

  12. 12.

    Fawer CL, Torrado A, Guignard JP (1979) Single injection clearance in the neonate. Biol Neonate 35:321–324

    CAS  Article  Google Scholar 

  13. 13.

    Pottel H (2017) Measuring and estimating glomerular filtration rate in children. Pediatr Nephrol 32:249–263

    Article  Google Scholar 

  14. 14.

    Sharma AP, Yasin A, Garg AX, Filler G (2011) Diagnostic accuracy of cystatin C-based eGFR equations at different GFR levels in children. Clin J Am Soc Nephrol 6:1599–1608

    CAS  Article  Google Scholar 

  15. 15.

    Bacchetta J, Cochat P, Rognant N, Ranchin B, Hadj-Aissa A, Dubourg L (2011) Which creatinine and cystatin C equations can be reliably used in children? Clin J Am Soc Nephrol 6:552–560

    CAS  Article  Google Scholar 

  16. 16.

    Andersen TB, Eskild-Jensen A, Frøkiaer J, Brøchner-Mortensen J (2009) Measuring glomerular filtration rate in children; can cystatin C replace established methods? A review. Pediatr Nephrol 24:929–941

    Article  Google Scholar 

  17. 17.

    Brion LP, Fleischman AR, McCarton C, Schwartz GJ (1986) A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: noninvasive assessment of body composition and growth. J Pediatr 109:698–707

    CAS  Article  Google Scholar 

  18. 18.

    Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin N Am 34:571–590

    CAS  Article  Google Scholar 

  19. 19.

    Guignard JP, Drukker A (1999) Why do newborn infants have a high plasma creatinine? Pediatrics 103:e49

    CAS  Article  Google Scholar 

  20. 20.

    Filler G, Guerrero-Kanan R, Alvarez-Elías AC (2016) Assessment of glomerular filtration rate in the neonate: is creatinine the best tool? Curr Opin Pediatr 28:173–179

    CAS  Article  Google Scholar 

  21. 21.

    Parvex P, Combescure C, Rodriguez M, Girardin E (2012) Is cystatin C a promising marker of renal function, at birth, in neonates prenatally diagnosed with congenital kidney anomalies? Nephrol Dial Transplant 27:3477–3482

    CAS  Article  Google Scholar 

  22. 22.

    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

    CAS  Article  Google Scholar 

  23. 23.

    Jetton JG, Askenazi DJ (2012) Update on acute kidney injury in the neonate. Curr Opin Pediatr 24:191–196

    CAS  Article  Google Scholar 

  24. 24.

    Leake RD, Trygstad CW, Oh W (1976) Inulin clearance in the newborn infant: relationship to gestational and postnatal age. Pediatr Res 10:759–762

    CAS  PubMed  Google Scholar 

  25. 25.

    Vieux R, Hascoet J-M, Merdariu D, Fresson J, Guillemin F (2010) Glomerular filtration rate reference values in very preterm infants. Pediatrics 125:e1186–e1192

    Article  Google Scholar 

  26. 26.

    Harmoinen A, Ylinen E, Ala-Houhala M, Janas M, Kaila M, Kouri T (2000) Reference intervals for cystatin C in pre- and full-term infants and children. Pediatr Nephrol 15:105–108

    CAS  Article  Google Scholar 

  27. 27.

    Bariciak E, Yasin A, Harrold J, Walker M, Lepage N, Filler G (2011) Preliminary reference intervals for cystatin C and beta-trace protein in preterm and term neonates. Clin Biochem 44:1156–1159

    CAS  Article  Google Scholar 

  28. 28.

    Finney H, Newman DJ, Thakkar H, Fell JME, Price CP (2000) Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child 82:71–75

    CAS  Article  Google Scholar 

  29. 29.

    Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady B, Furth SL, Munoz A (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453

    CAS  Article  Google Scholar 

Download references

Acknowledgments

We thank Dr. Riccardo Pfister and the neonatology unit of Geneva Children Hospital for helping the inclusion of infants and the Research Platform of Geneva Children Hospital for the technical support. We are indebted to Dolores Mosig, Pediatric Nephrology Laboratory, in Lausanne for the biological measurements of inulin. A final thanks to Mme Rosemary Sudan for translation and proofreading of the text.

Funding

Von Meissner Grant, PRD for clinical research Grant, Geneva University Hospital, grant number CGR 7121.

Author information

Affiliations

Authors

Contributions

Dr. Wilhelm-Bals and Prof. Parvex conceptualized and designed the study, collected the data carried out the initial analyses, drafted the initial manuscript, and reviewed and critically revised the manuscript for intellectual content.

C. Combescure designed the data collection instruments, carried out the statistical analyses, and reviewed and revised the manuscript.

Y. Daali designed the pharmacological analyses, carried out the pharmacological analyses, and reviewed and revised the manuscript.

Dr. Chehade coordinated and supervised data collection and reviewed and revised the manuscript.

All Authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Alexandra Wilhelm-Bals.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest relevant to this article to disclose. The results presented in this paper have not been published previously in whole or part, except in abstract form.

Ethical approval

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.

Financial disclosure

The authors have no financial relationships relevant to this article to disclose.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wilhelm-Bals, A., Combescure, C., Chehade, H. et al. Variables of interest to predict glomerular filtration rate in preterm newborns in the first days of life. Pediatr Nephrol 35, 703–712 (2020). https://doi.org/10.1007/s00467-019-04257-z

Download citation

Keywords

  • Glomerular filtration rate
  • Preterm
  • Newborns
  • Estimated glomerular filtration rate