Estimating glomerular filtration rate in youth with obesity and type 2 diabetes: the iCARE study equation

Abstract

Background

The validity of pediatric estimated glomerular filtration rate equations (eGFRs) in early stages of CKD including hyperfiltration is unknown. The purpose of this study was to develop an eGFR equation for adolescents with obesity and type 2 diabetes (T2D).

Methods

eGFRs were developed from iohexol-derived GFRs (iGFRs) in 26 overweight/obese (BMI > 85th percentile) youth and 100 with T2D from the iCARE (Improving renal Complications in Adolescents with T2D through REsearch) cohort. Twenty percent of the cohort was withheld as a validation dataset. Linear regression analyses were used to develop the best formula based on body size, sex, creatinine, urea, ± cystatin C. Comparable validity of commonly used eGFR equations was assessed.

Results

Mean age 15.4 + 2.4 years, BMI Z-score 2.5 + 1.2, 61% female, and mean iGFR 129.0 + 27.7 ml/min/ 1.73 m2. The best adjusted eGFR formula (ml/min/1.73 m2) was 50.7 × BSA0.816 × (height (cm)/creatinine)0.405 × 0.8994 if sex = female | 1 otherwise. It resulted in 53.8% of eGFRs within 10% of measured iGFR and 96.2% within 30%. Bland–Altman 95% limits of agreement in the external dataset were − 37.6 to 45.5 ml/min/1.73m2 (bias = 3.96), and the correlation was 0.62. This equation performed better than all previously published creatinine-based eGFRs. cystatin C did not significantly improve results; however, some other cystatin C formulas also performed well.

Conclusions

The iCARE equation provides a more accurate creatinine-based eGFR in obese youth with and without T2D. Further studies are warranted to evaluate within-subject variability and applicability to lower GFRs and other populations.

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Acknowledgements

Ms. Paula Maier of the GFR Lab and the Toxicology lab at the University of Rochester Medical Center for the assay of iohexol and calculations of GFR.

Funding

This study was funded by the Canadian Diabetes Association #OG-3-11-3354-AD (Diabetes Canada) and the Manitoba Health Research Council #1475 (Research Manitoba). Dr. Schwartz also has funding from the NIH NIDDK U24 DK082194.

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Authors

Contributions

Dr. Dart drafted the initial manuscript and assisted with participant enrollment and data collection. She is the guarantor and takes full responsibility for the contents of the article.

Dr. Blydt-Hansen, Dr. Chateau, Dr. Schwartz, and Dr. McGavock made critical revisions of the manuscript for important intellectual content.

Dr. Sharma made critical revisions of the manuscript for important intellectual content and performed the statistical analysis.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Acknowledgement to Ms. Paula Maier of the GFR Lab and the Toxicology lab at the University of Rochester Medical Center for the assay of iohexol and calculations of GFR.

Corresponding author

Correspondence to A. B. Dart.

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Conflict of interest

The iohexol (Omnipaque 300) was provided at no charge by GE Healthcare, Amersham Division (Princeton, NJ) for the purposes of this study following approval from Health Canada for this off-label use. The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Dart, A.B., McGavock, J., Sharma, A. et al. Estimating glomerular filtration rate in youth with obesity and type 2 diabetes: the iCARE study equation. Pediatr Nephrol 34, 1565–1574 (2019). https://doi.org/10.1007/s00467-019-04250-6

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Keywords

  • eGFR
  • Youth
  • Type 2 diabetes
  • Obese
  • Hyperfiltration