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Reference serum creatinine levels according to sex, age, and height in children with Down syndrome

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Abstract

Standard serum creatinine (S–Cr) levels in healthy children fluctuate with age and sex. However, it is unclear if this fluctuation in S–Cr levels is present for children with Down syndrome (DS) who show atypical growth rate. Therefore, we aimed to establish specific reference S–Cr levels for DS and compare them with the prevailing standard levels. We retrospectively reviewed 984 children with DS aged 3 months to 18 years who visited our medical center. Patients with diseases affecting S–Cr levels were excluded. We calculated the reference S–Cr levels according to sex, age, and length/height using medical records. A total of 3765 examinations of 568 children with DS were registered for this study. Ages and S–Cr levels were examined for boys (y = 0.032x + 0.20; r = 0.868, P < 0.0001), and girls (y = 0.024x + 0.23; r = 0.835, P < 0.0001). S–Cr levels in children aged >9 years were significantly higher in boys than in girls. The 430 children with DS aged 2–8 years were examined 1867 times. Height and S–Cr levels showed a significantly strong positive correlation (r = 0.670, P < 0.001) with regression equation y = 0.37x. The quintic equations calculated with S–Cr levels and length/height for boys (336 children, 2043 tests, r = 0.887) and girls (232 children, 1722 tests, r = 0.805) werey =  − 6.132x5 + 32.78x4 − 67.86x3 + 68.31x2 − 33.14x + 6.41, and y = 0.09542x5 + 1.295x4 − 6.401x3 + 10.35x2 − 6.746x + 1.772. All calculated results varied from the standard levels for healthy children.

Conclusion: This study established reference S–Cr levels and quintic equations specific for children with DS. These reference levels would be potentially useful in evaluating S–Cr levels and renal function in this population.

What is Known:

•Standard serum creatinine levels vary with age and sex to reflect muscle mass.

•Reference serum creatinine levels specific to children with Down syndrome who show growth rates different from those of healthy children have not been established.

What is New:

•Serum creatinine levels in children with Down syndrome showed different trajectories for sex, age, and length/height when compared with the standard levels for healthy children.

•This report on specific reference serum creatinine levels for children with Down syndrome is useful in the assessment of renal function in these children.

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable

Abbreviations

ASD:

Atrial septal defect

AVSD:

Atrioventricular septal defect

CAKUT:

Congenital anomalies of the kidney and urinary tract

CGN:

Chronic glomerulonephritis

CHD:

Congenital heart disease

DORV:

Double-outlet right ventricle

DS:

Down syndrome

MAE:

Mean absolute error

ME:

Mean error

PDA:

Patent ductus arteriosus

PFO:

Patent foramen ovale

RMSE:

Root mean square error

S–Cr:

Serum creatinine

TOF:

Tetralogy of Fallot

VSD:

Ventricular septal defect

VUR:

Vesicoureteral reflux

References

  1. Schwartz GJ, Haycock GB, Spitzer A (1976) Plasma creatinine and urea concentration in children: normal values for age and sex. J Pediatr 88:828–830

    Article  CAS  Google Scholar 

  2. Savory DJ (1990) Reference ranges for serum creatinine in infants, children and adolescents. Ann Clin Biochem 27(Pt 2):99–101

    Article  CAS  Google Scholar 

  3. Uemura O, Honda M, Matsuyama T, Ishikura K, Hataya H, Yata N, Nagai T, Ikezumi Y, Fujita N, Ito S, Iijima K, Kitagawa T (2011) Age, gender, and body length effects on reference serum creatinine levels determined by an enzymatic method in Japanese children: a multicenter study. Clin Exp Nephrol 15:694–699

    Article  CAS  Google Scholar 

  4. Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, Thorpe P (2015) Growth charts for children with Down syndrome in the United States. Pediatrics 136:e1204–e1211

    Article  Google Scholar 

  5. Hatch-Stein JA, Zemel BS, Prasad D, Kalkwarf HJ, Pipan M, Magge SN, Kelly A (2016) Body composition and BMI growth charts in children with Down syndrome. Pediatrics 138:e20160541

    Article  Google Scholar 

  6. Hook EB, Cross PK (1982) Paternal age and Down’s syndrome genotypes diagnosed prenatally: no association in New York state data. Hum Genet 62:167–174

    Article  CAS  Google Scholar 

  7. Mutton D, Alberman E, Hook EB (1996) Cytogenetic and epidemiological findings in Down syndrome, England and Wales 1989 to 1993. National Down Syndrome Cytogenetic Register and the Association of Clinical Cytogeneticists. J Med Genet 33:387–394

    Article  CAS  Google Scholar 

  8. Papavassiliou P, Charalsawadi C, Rafferty K, Jackson-Cook C (2015) Mosaicism for trisomy 21: a review. Am J Med Genet A 167A:26–39

    Article  Google Scholar 

  9. Bull MJ, Committee on G (2011) Health supervision for children with Down syndrome. Pediatrics 128:393–406

    Article  Google Scholar 

  10. Capone GT, Chicoine B, Bulova P, Stephens M, Hart S, Crissman B, Videlefsky A, Myers K, Roizen N, Esbensen A, Peterson M, Santoro S, Woodward J, Martin B, Smith D, Down Syndrome Medical Interest Group D-USAAHCW (2018) Co-occurring medical conditions in adults with Down syndrome: a systematic review toward the development of health care guidelines. Am J Med Genet A 176:116–133

    Article  Google Scholar 

  11. Malaga S, Pardo R, Malaga I, Orejas G, Fernandez-Toral J (2005) Renal involvement in Down syndrome. Pediatr Nephrol 20:614–617

    Article  Google Scholar 

  12. Nishino T, Endo S, Miyano H, Umeda C, Tomii Y, Watanabe Y, Nakagawa M, Kakegawa D, Fujinaga S (2020) Is the eGFR formula useful for evaluating the renal function of Down syndrome? Pediatr Int. https://doi.org/10.1111/ped.14539

  13. Stevens LA, Coresh J, Greene T, Levey AS (2006) Assessing kidney function--measured and estimated glomerular filtration rate. N Engl J Med 354:2473–2483

    Article  CAS  Google Scholar 

  14. Daschner M (2005) Drug dosage in children with reduced renal function. Pediatr Nephrol 20:1675–1686

    Article  Google Scholar 

  15. Stacul F, van der Molen AJ, Reimer P, Webb JA, Thomsen HS, Morcos SK, Almen T, Aspelin P, Bellin MF, Clement O, Heinz-Peer G, Contrast Media Safety Committee of European Society of Urogenital R (2011) Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 21:2527–2541

    Article  Google Scholar 

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

    Article  Google Scholar 

  17. Subrahmanyam AB, Mehta AV (1995) Renal anomalies in Down syndrome. Pediatr Nephrol 9:253–254

    Article  CAS  Google Scholar 

  18. Kallen B, Mastroiacovo P, Robert E (1996) Major congenital malformations in Down syndrome. Am J Med Genet 65:160–166

    Article  CAS  Google Scholar 

  19. Niamien-Attai C, Bacchetta J, Ranchin B, Sanlaville D, Cochat P (2017) Renal abnormalities in Down syndrome: A review. Arch Pediatr 24:1013–1018

    Article  CAS  Google Scholar 

  20. Stoll C, Dott B, Alembik Y, Roth MP (2015) Associated congenital anomalies among cases with Down syndrome. Eur J Med Genet 58:674–680

    Article  Google Scholar 

  21. Rankin J, Tennant PW, Bythell M, Pearce MS (2012) Predictors of survival in children born with Down syndrome: a registry-based study. Pediatrics 129:e1373–e1381

    Article  Google Scholar 

  22. Morris JK, Garne E, Wellesley D, Addor MC, Arriola L, Barisic I, Beres J, Bianchi F, Budd J, Dias CM, Gatt M, Klungsoyr K, Khoshnood B, Latos-Bielenska A, Mullaney C, Nelen V, Neville AJ, O'Mahony M, Queisser-Luft A, Randrianaivo H, Rankin J, Rissmann A, Rounding C, Sipek A, Stoianova S, Tucker D, de Walle H, Yevtushok L, Loane M, Dolk H (2014) Major congenital anomalies in babies born with Down syndrome: a EUROCAT population-based registry study. Am J Med Genet A 164A:2979–2986

    Article  Google Scholar 

  23. Kupferman JC, Druschel CM, Kupchik GS (2009) Increased prevalence of renal and urinary tract anomalies in children with Down syndrome. Pediatrics 124:e615–e621

    Article  Google Scholar 

  24. Toth R, Szanto P, Prodan Z, Lex DJ, Sapi E, Szatmari A, Gal J, Szanto T, Szekely A (2013) Down syndrome and postoperative complications after paediatric cardiac surgery: a propensity-matched analysis. Interact Cardiovasc Thorac Surg 17:691–697

    Article  Google Scholar 

  25. Greenberg JH, Zappitelli M, Devarajan P, Thiessen-Philbrook HR, Krawczeski C, Li S, Garg AX, Coca S, Parikh CR, Consortium T-A (2016) Kidney outcomes 5 years after pediatric cardiac surgery: the TRIBE-AKI study. JAMA Pediatr 170:1071–1078

    Article  Google Scholar 

  26. Huynh L, Rodriguez-Lopez S, Benisty K, Dancea A, Garros D, Hessey E, Joffe A, Joffe R, Mackie A, Palijan A, Paun A, Pizzi M, Zappitelli M, Morgan C (2020) Follow-up after neonatal heart disease repair: watch out for chronic kidney disease and hypertension! Pediatr Nephrol 35:2137–2145

    Article  Google Scholar 

  27. Beyer C (1993) Creatine measurement in serum and urine with an automated enzymatic method. Clin Chem 39:1613–1619

    Article  CAS  Google Scholar 

  28. Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, Hostetter T, Levey AS, Panteghini M, Welch M, Eckfeldt JH, National Kidney Disease Education Program Laboratory Working G (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  Google Scholar 

  29. Agamah ES, Webber LS, Lawrence M, Wattigney W, Berenson GS (1990) Serum creatinine and its relation to cardiovascular disease risk variables in children and young adults from a biracial community. The Bogalusa Heart Study. J Lab Clin Med 116:327–334

    CAS  PubMed  Google Scholar 

  30. Groesbeck D, Kottgen A, Parekh R, Selvin E, Schwartz GJ, Coresh J, Furth S (2008) Age, gender, and race effects on cystatin C levels in US adolescents. Clin J Am Soc Nephrol 3:1777–1785

    Article  CAS  Google Scholar 

  31. Liu C, Wen J, Xiang J, Ouyang X, Yang Y, Lu W, Wang J, Huang J, Min X (2019) Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0-18 years old). J Int Med Res 47:3151–3159

    Article  CAS  Google Scholar 

  32. Ghasemi A, Azimzadeh I, Afghan M, Momenan AA, Bagheripour F, Azizi F (2015) Pediatric reference values for serum creatinine and estimated glomerular filtration rate in Iranians: Tehran Lipid and Glucose Study. Arch Iran Med 18:753–759

    PubMed  Google Scholar 

  33. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank Dr. Uemura for his kind advice.

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Authors and Affiliations

  1. Division of Nephrology, Saitama Children’s Medical Center, 1-2 Shintoshin, Chuo-ku, Saitama-City, Saitama, 330 8777, Japan

    Tomohiko Nishino, Shota Endo, Hiroki Miyano, Yoichi Takemasa, Masahito Saito, Chisato Umeda, Yuji Tomii, Yoshitaka Watanabe, Mayu Nakagawa, Daisuke Kakegawa & Shuichiro Fujinaga

  2. Department of Pediatrics, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

    Tomohiko Nishino

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  1. Tomohiko Nishino
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  2. Shota Endo
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Contributions

Tomohiko Nishino mainly drafted the manuscript and performed the statistical analysis; Tomohiko Nishino, Shota Endo, Hiroki Miyano, Yoichi Takemasa, Masahito Saito, Chisato Umeda, and Yuji Tomii contributed to the conception and design of this study; Yoshitaka Watanabe, Mayu Nakagawa, and Daisuke Kakegawa critically reviewed the manuscript; Shuichiro Fujinaga supervised the whole study process. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Tomohiko Nishino.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the local ethics committee for human research (protocol number 2020-04-025). All procedures involving human participants were conducted according to the ethical standards of the institutional and/or national research committee and within the guidelines of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The requirement for informed consent was waived by the institutional review board due to the retrospective nature of the study.

Consent for publication

In consideration of human rights and ethics, this research was conducted under the review of the ethics committee of the medical center, and the study plan outline was presented on our center’s website, where patients and parents could ask questions about the study and opt-out from the use of their data.

Conflict of interest

The authors declare no competing interests.

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Communicated by Gregorio Paolo Milani

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Nishino, T., Endo, S., Miyano, H. et al. Reference serum creatinine levels according to sex, age, and height in children with Down syndrome. Eur J Pediatr 180, 2977–2983 (2021). https://doi.org/10.1007/s00431-021-04078-z

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