A novel method for creatinine adjustment makes the revised Lund–Malmö GFR estimating equation applicable in children

Abstract

The aim of this study was to establish creatinine growth curves separately for males and females that can be used to adjust childhood levels of serum creatinine to corresponding adult levels. Linear regression with fractional polynomials of age as independent variable was used to construct creatinine growth curves for a reference cohort (n ¼ 83,157 samples from Belgium and Sweden, age 2-40 years). Adjusted creatinine obtained from the growth curves was used to improve accuracy of estimated glomerular filtration rate (eGFR) based on the Lund-Malm€ o revised (LMR) equation in children. The LMR equation based on creatinine values adjusted to age 18 years was validated against measured GFR (mGFR) in a separate cohort of 4005 children from four different European countries. Validation metrics included median bias, precision, and accuracy expressed as percentage of estimates within ±30% (P 30) of mGFR. Remarkable improvements in bias and accuracy were observed; P 30 increased from 56% to 74% after creatinine adjustments in children with mGFR <75 mL/min/1.73 m 2 (n ¼ 932), while P 30 was relatively unchanged (89-90%) at mGFR !75 mL/min/1.73 m 2 (n ¼ 3073). The suggested approach with adjusted creatinine makes LMR applicable in children irrespective of their renal function.

Estimation of the glomerular filtration rate in children and young adults by means of the CKD-EPI equation with age-adjusted creatinine values

“…Additional validations also included LMR18, i.e. the LMR equation with age and creatinine values adjusted to 18 years in children (LMR18) 9 , and are presented in Table S8. In CKD-EPI40 the age-adjustment of creatinine continues until age 40, whereas the adjustment stops at age 18 with LMR, which means that LMR18 yields the same estimates as the original LMR equation in all adults.…”

“…The accuracy of CKD-EPI40 was equal compared to the revised Lund-Malmö 18-year equation when validated in the same paediatric cohort. 9 CKD-EPI40 exhibited at least 75% P 30 accuracy at mGFR 55 -160 mL/min/1.73 m 2 , which included 87% of the children referred for GFR measurements in this paediatric nephrology setting. The estimated P 30 accuracy was 86% at the 75 mL/min/1.73 m 2 suggested CKD threshold for children.…”

“…Our proposed adjustment strategy for creatinine during childhood and young adulthood is generally applicable 9 . It has four important strengths: (i) the original coefficients of the GFR equation can be used, (ii) the same equation can for most patients be used across the entire lifespan without artificial changes in eGFR e.g.…”

“…We have recently demonstrated how creatinine growth curves can be used to recalculate (adjust) childhood levels of serum creatinine to corresponding adult levels 9 . One advantage with this method is that it can be used with any pre-existing adult-equation to extend its applicability to children.…”

“…We noted remarkable improvements in bias and accuracy of the Lund-Malmö Revised (LMR) equation when applying the equation on age-adjusted creatinine concentrations in children with CKD. 9 Using the same approach, the aim of the present study was to investigate if age-adjustment of serum creatinine concentrations can make the CKD-EPI equation applicable in children (2-17 years) and increase accuracy in young adults (18-39 years).…”