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Klin Padiatr 2018; 230(03): 142-150
DOI: 10.1055/a-0587-5753
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

A Comparison of GFR Estimation Formulae in Pediatric Oncology

Ein Vergleich von GFR Schätzformeln in der pädiatrischen Onkologie
Tobias Rechenauer
1   Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany
,
Jakob Zierk
1   Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany
,
Daniel Gräfe
2   Department for Pediatric Radiology, University Hospital Leipzig, Leipzig, Germany
,
Wolfgang Rascher
1   Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany
,
Manfred Rauh
1   Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany
,
Markus Metzler
1   Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany
› Author Affiliations
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Publication History

Publication Date:
09 April 2018 (online)

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Abstract

Background Application of potentially nephrotoxic chemotherapy requires continuous monitoring of renal function for toxicity and dosing. Novel pediatric glomerular filtration rate (GFR) estimating equations including cystatin C have been proposed to enhance the reliability of GFR calculation.

Materials and methods We examined a pediatric oncologic data set with a total of 363 GFR measurements. An analysis of distribution characteristics and comparison of medians was performed to compare creatinine and cystatin C-based GFR estimating formulae. Furthermore, we investigated the clinical impact of different equations in regard to therapeutic consequences.

Results Significant differences in estimated GFR values were calculated depending on the applied formula (range of median GFR from 94.8 to 180.9 mL/min per 1.73 m2) which may result in different therapeutic consequences for the use of potentially nephrotoxic chemotherapeutic agents. Significant correlation for all examined formulae was identified, however there were large fluctuations among the correlation coefficients ranging from 0.254 to 1.0.

Conclusion This study compares proposed pediatric GFR estimating equations in a clinical setting. It underlines the current limitations and difficulties of GFR estimation including potential dosing errors. Cystitis C-based equations can be used as alternatives to creatinine-based estimations when the appropriate laboratory method has been applied. A comparative calculator for pediatric GFR estimating equations along with background information is provided at http://gfr.pedz.de and may support clinical decision-making.

Zusammenfassung

Hintergrund Das Verabreichen von chemotherapeutischen Substanzen mit potentieller Nephrotoxizität setzt ein kontinuierliches Monitoring der renalen Funktion für mögliche Dosisanpassungen voraus. Zur Erhöhung der Reliabilität einer Schätzung der glomerulären Filtrationsrate (GFR) werden in der Pädiatrie zunehmend Cystatin C basierte Formeln vorgeschlagen.

Material und Methoden Wir untersuchten ein pädiatrisch onkologisches Kollektiv mit insgesamt 363 GFR Messungen. Eine deskriptiv statistische Analyse mit Verteilungsverhalten der Mediane wurde durchgeführt um Kreatinin und Cystatin C-basierte GFR Schätzformeln zu vergleichen. Zudem wurden die klinischen Implikationen der unterschiedlichen Formeln im Hinblick auf therapeutische Konsequenzen untersucht.

Ergebnisse Es zeigten sich signifikante Unterschiede der geschätzten GFR Werte in Abhängigkeit der benutzen Formel (Spannweite Median 94.8 bis 180.9 mL/min pro 1.73 m2) die zu unterschiedlichen therapeutischen Konsequenzen für die Nutzung potentiell nephrotoxischer Substanzen führen können. Es ergab sich eine signifikante Korrelation zwischen allen untersuchten Formeln, allerdings zeigte sich eine große Fluktuation des Korrelationskoeffizienten von 0.254 bis 1.0.

Schlussfolgerung Diese Studie vergleicht vorgeschlagene GFR Formeln in einem klinischen Setting. Sie zeigt die derzeitigen Limitationen und Probleme einer GFR Schätzung inklusive potentieller Dosierungsfehler auf. Cystatin C basierte Formeln können benutzt werden, wenn die geeignete Labormethode gegeben ist. Eine Hilfestellung mit Hintergrundinformation ist unter http://gfr.pedz.de gegeben um klinische Entscheidungsfindungen zu erleichtern.

Key words

renal function - cystatin C - GFR - glomerular filtration rate estimating equation - creatinine clearance - nephrotoxic substances

Schlüsselwörter

Nierenfunktion - Cystatin C - GFR - Schätzformeln glomeruläre Filtrationsrate - Kreatinin Clearance - nephrotoxische Substanzen
 

  • References

  • 1 Berlyne GM, Varley H, Nilwarangkur S. et al. Endogenous-creatinine clearance and glomerular-filtration rate. Lancet 1964; 2: 874-876
    PubMedGoogle Scholar
  • 2 Bokenkamp A, Domanetzki M, Zinck R. et al. Cystatin C – a new marker of glomerular filtration rate in children independent of age and height. Pediatrics 1998; 101: 875-881
    CrossrefPubMedGoogle Scholar
  • 3 Bokenkamp A, van Wijk JA, Lentze MJ. et al. Effect of corticosteroid therapy on serum cystatin C and beta2-microglobulin concentrations. Clinical chemistry 2002; 48: 1123-1126
    CrossrefPubMedGoogle Scholar
  • 4 Bouvet Y, Bouissou F, Coulais Y. et al. GFR is better estimated by considering both serum cystatin C and creatinine levels. Pediatric nephrology 2006; 21: 1299-1306
    CrossrefPubMedGoogle Scholar
  • 5 Counahan R, Chantler C, Ghazali S. et al. Estimation of glomerular filtration rate from plasma creatinine concentration in children. Archives of disease in childhood 1976; 51: 875-878
    CrossrefPubMedGoogle Scholar
  • 6 Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis. American journal of kidney diseases: The official journal of the National Kidney Foundation 2002; 40: 221-226
    CrossrefPubMedGoogle Scholar
  • 7 Dodgshun AJ, Quinlan C, Sullivan MJ. Cystatin C Based equation accurately estimates glomerular filtration rate in children with solid and central nervous system tumours: Enough evidence to change practice?. Pediatr Blood Cancer 2016; 63: 1535-1538
    CrossrefPubMedGoogle Scholar
  • 8 Filler G, Lepage N. Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula?. Pediatric nephrology 2003; 18: 981-985
    CrossrefPubMedGoogle Scholar
  • 9 Filler G, Priem F, Vollmer I. et al Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate. Pediatric nephrology 1999; 13: 501-505
    CrossrefPubMedGoogle Scholar
  • 10 Groninger E, Proost JH, de Graaf SS. Pharmacokinetic studies in children with cancer. Crit Rev Oncol Hematol. 2004; 52: 173-197
    CrossrefPubMedGoogle Scholar
  • 11 Grubb A, Horio M, Hansson LO. et al. Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator. Clinical chemistry 2014; 60: 974-986
    CrossrefPubMedGoogle Scholar
  • 12 Grubb A, Nyman U, Bjork J. et al. 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. Clinical chemistry 2005; 51: 1420-1431
    CrossrefPubMedGoogle Scholar
  • 13 Grubb AO. Cystatin C--properties and use as diagnostic marker. Advances in clinical chemistry 2000; 35: 63-99
    PubMedGoogle Scholar
  • 14 Herget-Rosenthal S, Trabold S, Huesing J. et al. Cystatin C – an accurate marker of glomerular filtration rate after renal transplantation?. Transpl Int 2000; 13: 285-289
    CrossrefPubMedGoogle Scholar
  • 15 Horio M, Imai E, Yasuda Y. et al. GFR estimation using standardized serum cystatin C in Japan. American journal of kidney diseases: The official journal of the National Kidney Foundation 2013; 61: 197-203
    CrossrefPubMedGoogle Scholar
  • 16 Hughes RG, Edgerton EA. Reducing pediatric medication errors: children are especially at risk for medication errors. Am J Nurs. 2005; 105: 79-80 82, 85 passim
    PubMedGoogle Scholar
  • 17 Inker LA, Schmid CH, Tighiouart H. et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. The New England journal of medicine 2012; 367: 20-29
    CrossrefPubMedGoogle Scholar
  • 18 Koren G. Therapeutic drug monitoring principles in the neonate. National Academy of Clinical Biochemistry. Clinical chemistry 1997; 43: 222-227
    CrossrefPubMedGoogle Scholar
  • 19 National Kidney Foundation . K/DOQI Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. American journal of kidney diseases: The official journal of the National Kidney Foundation 2002; 39 (Suppl. 01) S1-266 Table 224 (page S256)
    PubMedGoogle Scholar
  • 20 National Kidney Foundation . K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, classification, and stratification. American journal of kidney diseases: the official journal of the National Kidney Foundation 2002; 39 (Suppl. 01) S1-S266
    PubMedGoogle Scholar
  • 21 Rehberg PB. Studies on Kidney Function: The Rate of Filtration and Reabsorption in the Human Kidney. The Biochemical journal 1926; 20: 447-460
    CrossrefPubMedGoogle Scholar
  • 22 Schwartz GJ, Haycock GB, Edelmann Jr. CM. et al. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58: 259-263
    CrossrefPubMedGoogle Scholar
  • 23 Schwartz GJ, Munoz A, Schneider MF. et al. New equations to estimate GFR in children with CKD. Journal of the American Society of Nephrology: JASN 2009; 20: 629-637
    CrossrefPubMedGoogle Scholar
  • 24 Schwartz GJ, Schneider MF, Maier PS. et al. Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney international 2012; 82: 445-453
    CrossrefPubMedGoogle Scholar
  • 25 Stevens LA, Coresh J, Greene T. et al. Assessing kidney function--measured and estimated glomerular filtration rate. The New England journal of medicine 2006; 354: 2473-2483
    CrossrefPubMedGoogle Scholar
  • 26 Stevens LA, Schmid CH, Greene T. et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney international 2009; 75: 652-660
    CrossrefPubMedGoogle Scholar
  • 27 Stickle D, Cole B, Hock K. et al. Correlation of plasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population. Clinical chemistry 1998; 44 6 Pt 1 1334-1338
    CrossrefPubMedGoogle Scholar
  • 28 van Acker BA, Koomen GC, Koopman MG. et al. Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate. Lancet 1992; 340: 1326-1329
    CrossrefPubMedGoogle Scholar
  • 29 Weber JA, van Zanten AP. Interferences in current methods for measurements of creatinine. Clinical chemistry 1991; 37: 695-700
    CrossrefPubMedGoogle Scholar
  • 30 Zappitelli M, Parvex P, Joseph L. et al. Derivation and validation of cystatin C-based prediction equations for GFR in children. American journal of kidney diseases: The official journal of the National Kidney Foundation 2006; 48: 221-230
    CrossrefPubMedGoogle Scholar