I. How to Use
When to Use
This calculator is appropriate for estimating the glomerular filtration rate (GFR) of children and young adults aged 1-25 years who have mild to moderate chronic kidney disease (CKD).
eGFR is an estimate of kidney function and can be tracked over time to assess a patient’s kidney function and risk of CKD progression.
These U25 equations can be used when the individual’s age, sex, and height, as well as recent serum creatinine and/or cystatin C values, are known. If both creatinine and cystatin C are available, averaging the results of the U25sCr and U25cysC GFR estimates improves precision compared with either equation alone. The U25 equations should not be used in acute kidney injury (AKI), where kidney function is rapidly changing.1
Pearls / Pitfalls
The CKiD U25 formula tends to overestimate GFR for underweight children and adolescents, but performs well for those in normal, overweight, and obese habitus categories.2 Otherwise, it is statistically unbiased with respect to age and sex.3
The U25sCr and U25cysC equations can be appropriate in different contexts. The U25 equations were derived in children and young adults with CKD and may be less accurate in individuals with normal kidney function (eGFR >90 mL/min/1.73 m²). It is also important to note that serum creatinine values can be erroneously influenced by decreased muscle mass and certain medications. Thus, cystatin C–based estimates may be helpful when muscle mass is reduced or creatinine reliability is questioned.1
When clinically available, both the U25sCr and U25cysC can be used to average the eGFR of the two equations, producing a result that is both more accurate and precise for patients with mild to moderate CKD.1
When interpreting results, clinicians should consider the laboratory assays used to measure sCr and cystatin C. Although the Jaffe and enzymatic creatinine assays generally produce comparable results, the same assay should be used for longitudinal monitoring whenever possible to minimize variability.4 In the United States, cystatin C assays became standardized to International Federation of Clinical Chemistry (IFCC) reference material beginning in 2018. Because the current CKiD U25 equations were developed using IFCC-standardized cystatin C measurements, values obtained prior to standardization may not be directly comparable.5
Why Use
The CKiD U25 equations were developed with data from CKiD, a large North American pediatric CKD cohort. Compared with the 2009 CKiD “bedside” equation, the U25 equations provide improved performance across a broader age range (1 - 25 years), particularly in children under 5 years and young adults over 18 years.3
The U25 equations provide flexibility by allowing use of creatinine, cystatin C, or both. In accordance with current National Kidney Foundation and American Society of Nephrology guidance, the CKiD U25 calculator does not use race as a variable in its estimations.6
Some data suggest that the U25 equations may outperform CKD-EPI in young adults with childhood-onset CKD.3
II. Next Steps
Advice
As always, defer to clinical judgement. In children and adolescents over the age of 2 years, KDIGO guidelines consider an eGFR <90 mL/min/1.73 m² to be decreased, and cause for further evaluation. Chronic kidney disease is defined by abnormalities in kidney function or structure persisting ≥3 months. eGFR is just one metric describing renal health, and should be contextualized using an appropriate kidney failure risk prediction equation when considering treatment options for patients with CKD.7 The U25 equation should not be used for management of acute kidney injury.
Management
Patients with persistently reduced eGFR should undergo repeat eGFR testing to monitor longitudinal change. Further evaluation of relevant history, physical examination (blood pressure, growth parameters) and relevant diagnostic testing (urine albumin-to-creatinine ratio (ACR) or protein quantification) may be appropriate. Existing medications should be evaluated for nephrotoxins and doses adjusted based on most recent eGFR. A key element of pediatric CKD management is annual, or more frequent, monitoring of eGFR and albuminuria. Children with CKD should be encouraged to undertake ≥60 minutes of appropriate physical activity daily and maintain a healthy weight.7 Refer to KDIGO 2024 guidelines for comprehensive CKD management recommendations.
Critical Actions
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Repeat measurements if abnormal
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Monitor GFR trends to track CKD progression
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Adjust medication dosing based on most recent eGFR
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Consider referral to nephrology for persistently abnormal GFR (<90 mL/min/1.73 m²) or for significant kidney damage markers (i.e., urine ACR ≥ 30mg/g, urine PCR ≥ 200mg/g, persistent hematuria).7
III. Evidence
Evidence Appraisal
The CKiD U25 eGFR equations have been developed using 2655 observations from 928 participants in the Chronic Kidney Disease in Children (CKiD) study. CKiD is a large, well-established, multicenter, prospective cohort of children and young adults with mild to moderate CKD across the United States and Canada.1 The equations have been externally validated in European and North American cohorts and compared with CKD-EPI and other pediatric formulas.2,8,9,10 However, their performance is less certain for infants, those with normal kidney function (eGFR > 90), and populations outside studied cohorts. The U25 CKiD eGFR equations are supported for clinical use by the current 2024 KDIGO guidelines.7
Formula
CKiD U25 Creatinine
\[\mathrm{eGFR}=\mathrm{k} \times(\text {height, } \mathrm{m} / \mathrm{sCr,} \ \mathrm{mg} / \mathrm{dL})\]
CKiD U25 Cystatin C
\[\mathrm{eGFR}=\mathrm{k} \times(1 / \text{cysC, mg/L})\]
CKiD U25 Creatinine-Cystatin C
\[\mathrm{eGFR}=(\text{sCr-based eGFR} + \text{cysC-based eGFR}) / 2\]
Facts & Figures
Precision of eGFR equations is commonly expressed as P30, the percentage of estimates within 30% of measured GFR. The table below shows the P(30) values for the U25 CKiD equations for children and young adult age groups.1,3
Literature
Original/Primary
Pierce CB, Muñoz A, Ng DK, Warady BA, Furth SL, Schwartz GJ. Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease. Kidney International. 2021;99(4):948-956.
Validation
[2] Validating CKiD U25 eGFR Equations for Differing Body Habitus
Pierce CB, Ng DK, Warady BA. Validating CKiD U25 EGFR Equations for Differing Body Habitus. Journal of the American Society of Nephrology. 2023;34(11S):821-822. doi:10.1681/asn.20233411s1821c
Nyman U, Björk J, Berg U, et al. The Modified CKiD Study Estimated GFR Equations for Children and Young Adults Under 25 Years of Age: Performance in a European Multicenter Cohort. American Journal of Kidney Diseases. 2022;80(6):807-810. doi:10.1053/j.ajkd.2022.02.018
[9] Performance of GFR Estimating Equations in Young Adults
Inker LA, Tighiouart H, Adingwupu OM, et al. Performance of GFR Estimating Equations in Young Adults. American Journal of Kidney Diseases. 2024;83(2):272-276. doi:10.1053/j.ajkd.2023.06.008
Filler G, Ahmad F, Bhayana V, Díaz González de Ferris ME, Sharma AP. Limitations of U25 CKiD and CKD-epi EGFR Formulae in Patients 2–20 years of Age With Measured GFR > 60 ml/min/1.73 m2—a Cross-Sectional Study. Pediatric Nephrology. 2023;39(4):1169-1176. doi:10.1007/s00467-023-06185-5
Other References
Ng DK, Pierce CB. Kidney Disease Progression in Children and Young Adults with Pediatric CKD: Epidemiologic Perspectives and Clinical Applications. Seminars in Nephrology. 2021;41(5):405-415. doi:10.1016/j.semnephrol.2021.09.002
Osmic-Husni A, Hukic F, Saric MP. Comparison of Jaffe Method and Enzymatic Method at Measuring Serum Creatinine Level, Creatinine Clearance and Estimated Glomerular Filtration Rate. Mater Sociomed. 2023;35(2):113-117. doi:10.5455/msm.2023.35.113-117
[5] Recalibration of cystatin C using standardized material in Siemens nephelometers
Schwartz GJ, Cox C, Seegmiller JC, et al. Recalibration of cystatin C using standardized material in Siemens nephelometers. Pediatr Nephrol. Feb 2020;35(2):279-285. doi:10.1007/s00467-019-04389-2
Delgado C, Baweja M, Crews DC, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. American Journal of Kidney Diseases. 2022;79(2). doi:10.1053/j.ajkd.2021.08.003
Stevens PE, Ahmed SB, Carrero JJ, et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International. 2024;105(4). doi:10.1016/j.kint.2023.10.018