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Trajectories of eGFR and risk of albuminuria in youth with type 2 diabetes: results from the TODAY cohort study

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Abstract

Background

We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

Methods

Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories.

Results

At baseline, participants’ mean age was 14 years, type 2 diabetes duration was 6 months, mean HbA1c was 6%, and mean eGFR was 120 ml/min/1.73 m2. Five eGFR trajectories associated with different rates of albuminuria were identified, including a “progressive increasing eGFR” group (10%), three “stable eGFR” groups with varying starting mean eGFR, and an “eGFR steady decline” group (1%). Participants who exhibited the greatest peak eGFR also had the highest levels of elevated albuminuria at year 10. This group membership was characterized by a greater proportion of female and Hispanic participants.

Conclusions

Distinct eGFR trajectories that associate with albuminuria risk were identified, with the eGFR trajectory characterized by increasing eGFR over time associating with the highest level of albuminuria. These descriptive data support the current recommendations to estimate GFR annually in young persons with type 2 diabetes and provide insight into eGFR-related factors which may contribute to predictive risk strategies for kidney disease therapies in youth with type 2 diabetes.

Trial registration

ClinicalTrials.gov Identifier: NCT00081328, date registered 2002.

Graphical abstract

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Data availability

Data collected for the TODAY/TODAY2 studies are available to the public through the NIDDK Repository: https://repository.niddk.nih.gov/studies/today/.

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Acknowledgements

We thank all the members of the TODAY Study Group not included among the authors. A complete list of individuals can be found at https://www.nejm.org/doi/suppl/10.1056/NEJMoa2100165/suppl_file/nejmoa2100165_appendix.pdf. The TODAY Study Group thanks the following companies for donations in support of the study’s efforts: Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc.; Pfizer; and Sanofi Aventis. We also gratefully acknowledge the participation and guidance of the American Indian partners associated with the clinical center located at the University of Oklahoma Health Sciences Center, including members of the Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, Choctaw Nation of Oklahoma, and Oklahoma City Area Indian Health Service; the opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the respective Tribes and the Indian Health Service.

Funding

This work was completed with funding from NIDDK and the NIH Office of the Director through grants U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The NIDDK project office was involved in all aspects of the study, including design and conduct; collection, management, analysis, and interpretation of the data; review and approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. The Biostatistics Center, George Washington University, 6110 Executive Boulevard, Suite 750, Rockville, MD, 20852, USA

    Laure El ghormli, Hui Wen & Diane Uschner

  2. Baylor College of Medicine Children’s Nutrition Research Center, Houston, TX, USA

    Morey W. Haymond

  3. UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Kara S. Hughan

  4. UH Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, OH, USA

    Katherine Kutney

  5. Joslin Diabetes Center, Boston, MA, USA

    Lori Laffel

  6. Department of Pediatrics, Saint Louis University Health Sciences Center, St. Louis, MO, USA

    Sherida E. Tollefsen

  7. The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Elia N. Escaname & Jane Lynch

  8. University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, CO, USA

    Petter Bjornstad

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  1. Laure El ghormli
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for the TODAY Study Group

Contributions

L. E., J. L., and P. B. designed the analyses and wrote the manuscript. L. E. and W. H. conducted the statistical analyses and prepared the tables and figures. D. U., M. W. H., K. H., K. K., L. L., S. T., and E. N. E. contributed to interpretation of the data and reviewed and edited the manuscript.

Corresponding author

Correspondence to Laure El ghormli.

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The authors declare no competing interests.

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Jane Lynch and Petter Bjornstad contributed equally to this work.

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El ghormli, L., Wen, H., Uschner, D. et al. Trajectories of eGFR and risk of albuminuria in youth with type 2 diabetes: results from the TODAY cohort study. Pediatr Nephrol 38, 4137–4144 (2023). https://doi.org/10.1007/s00467-023-06044-3

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