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Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children

Björk, Jonas LU ; Nyman, Ulf LU ; Berg, Ulla; Delanaye, Pierre; Dubourg, Laurence; Goffin, Karolien; Grubb, Anders LU ; Hansson, Magnus; Littmann, Karin and Åsling-Monemi, Kajsa, et al. (2019) In Pediatric Nephrology
Abstract

Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres. Methods: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2–17 years. Validated equations included Schwartz-2009CR/2012CR/CYS/CR+CYS, FASCR/CYS/CR+CYS, LMRCR,... (More)

Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres. Methods: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2–17 years. Validated equations included Schwartz-2009CR/2012CR/CYS/CR+CYS, FASCR/CYS/CR+CYS, LMRCR, Schwartz-LyonCR, BergCYS, CAPACYS, CKD-EPICYS, AndersenCR+CYS and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P10) and ± 30% (P30) of mGFR. Results: Three of the cystatin C equations, BergCYS, CAPACYS and CKD-EPICYS, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPICYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-LyonCR had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m2 and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations. Conclusions: The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations.

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@article{f10d7067-1fc6-4481-84f5-97c4e4a9f22e,
  abstract     = {<p>Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres. Methods: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2–17 years. Validated equations included Schwartz-2009<sub>CR</sub>/2012<sub>CR/CYS/CR+CYS</sub>, FAS<sub>CR/CYS/CR+CYS</sub>, LMR<sub>CR</sub>, Schwartz-Lyon<sub>CR</sub>, Berg<sub>CYS</sub>, CAPA<sub>CYS</sub>, CKD-EPI<sub>CYS</sub>, Andersen<sub>CR+CYS</sub> and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P<sub>10</sub>) and ± 30% (P<sub>30</sub>) of mGFR. Results: Three of the cystatin C equations, Berg<sub>CYS</sub>, CAPA<sub>CYS</sub> and CKD-EPI<sub>CYS</sub>, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPI<sub>CYS</sub> had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-Lyon<sub>CR</sub> had the best performance but was inaccurate at mGFR &lt; 30 mL/min/1.73 m<sup>2</sup> and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations. Conclusions: The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations.</p>},
  author       = {Björk, Jonas and Nyman, Ulf and Berg, Ulla and Delanaye, Pierre and Dubourg, Laurence and Goffin, Karolien and Grubb, Anders and Hansson, Magnus and Littmann, Karin and Åsling-Monemi, Kajsa and Bökenkamp, Arend and Pottel, Hans},
  issn         = {0931-041X},
  keyword      = {Children,Chronic kidney disease,Glomerular filtration rate,Kidney function tests,Renal failure},
  language     = {eng},
  month        = {02},
  publisher    = {Springer},
  series       = {Pediatric Nephrology},
  title        = {Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children},
  url          = {http://dx.doi.org/10.1007/s00467-018-4185-y},
  year         = {2019},
}