This study aimed to determine the most accurate equation for estimating GFR in children. It examined the potential of equations that use serum creatinine or Cystatin C alone or in combinations as indicators of kidney disease using the revised Schwartz CKiD formula as the reference standard.
Among the evaluated equations, the Pottel height-independent equation had the highest discriminant value, accuracy, precision, and agreement with the validated Schwartz CKiD formula.
The Pottel equation, suitable for populations with high stunted growth rates, provides simplicity by using readily available serum creatinine as a biomarker and not depending on height as a factor.26, 27 The adaptability of the Pottel equation enhances its accessibility, particularly in resource-limited settings, where comprehensive biomarker panels are scarce. Its accurate GFR estimation from a single biomarker aligns with existing literature, reinforcing our report's credibility.16, 17, 28
On the other hand, the Bouvet equation exhibited the lowest precision and accuracy in eGFR estimation, suggesting that it may not effectively estimate eGFR in African children with values below 60 ml/min/1.73 m2, in tandem with its performance in Canadian children as reported by Sharma et al.29 Despite prior studies30, 31 highlighting the efficacy of GFR estimation equations using combined kidney disease biomarkers (e.g., Bouvet), our findings emphasize the need to assess equation performance across a range of GFR levels.24 The Bouvet equation, despite its use of biomarkers, performed poorly compared to the Pottel equation, which relied solely on serum creatinine. This underscores the significance of serum creatinine and the need to choose the most accurate equation for assessing renal function in specific populations.32 It is also significant to acknowledge that the performance of equations depends on their context of development.
The similar performance of Chehade and Pottel equations in our study may be due to their shared characteristic of not being heavily influenced by height, unlike other equations. While Pottel is explicitly height-independent, Chehade accommodates children with various height statuses.24, 33
Our study revealed that estimation equations varied in accuracy and ability to classify measured GFR correctly. Bouvet exhibited superior discrimination but lower accuracy when compared to Zapettelli's equation in estimating eGFR. This highlights the importance of considering both aspects when selecting the most suitable CKD equation for a specific context. This is significant due to the far-reaching implications of CKD diagnosis, including economic consequences, psychological impact on patients and families, and other intangible effects on individuals. An optimal eGFR estimation formula should excel in both discrimination and accuracy. The Chehade and Pottel formulae meet these criteria for screening CKD in children.
Our study, like all others, has strengths and limitations. This community-based study, which used serum creatinine and cystatin C to evaluate participants with different levels of renal function in real-world settings, has shown that our eGFR estimation method is accurate and may have applicability across populations. This makes it an ideal screening tool for children at risk of developing chronic kidney disease. Additionally, the larger sample size in our study further enhances its external validity.
We used the pediatric Schwartz CKiD equation as our benchmark instead of measured GFR, which is the standard approach. GFR measurement may not be feasible in a community setting.
The Schwartz CKiD equation was validated against iohexol-GFR, achieving 87.7% agreement within 30% of the iohexol-GFR estimates and 45.6% agreement within 10% of the iohexol-GFR estimates, supporting its validity as a reference standard.34
Due to limited funding and the prohibitive cost of enzymatic assays, we utilized the more affordable Jaffe's method for serum creatinine measurements in our study. Comparisons were made using the Schwartz CKiD equation, which relies on enzymatic assays known for accuracy at lower creatinine levels, despite the study's focus on individuals with lower GFR (higher creatinine values). However, the Jaffe method tends to overestimate serum creatinine at low concentrations due to non-creatinine interferences.
Standardizing the Jaffe method to IDMS National Institute of Standards and Technology Standard Reference Material (NIST SRM) 967 demonstrated comparable accuracy to IDMS traceable enzymatic assays, offering a practical alternative. We corrected the Jaffe method using the IDMS traceable creatinine equation which make the old Schwartz formula unsuitable. Caution is advised in interpreting the data, as estimated eGFRs may be inaccurately low. Consequently, this study may have overdiagnosed or misclassified CKD due to incomplete elimination of chromogenic interference by the IDMS traceable technique.