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Relationship between biomarkers of tubular injury and intrarenal hemodynamic dysfunction in youth with type 1 diabetes

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Abstract

Background

Early identification of youth with type 1 diabetes (T1D) at risk for diabetic kidney disease may improve clinical outcomes. We examined the cross-sectional relationship between kidney biomarkers neutrophil gelatinase–associated lipocalin (NGAL), copeptin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), chitinase-3-like protein-1 (YKL-40), and monocyte chemoattractant protein-1 (MCP-1) and intrarenal hemodynamic function in adolescents with T1D.

Methods

Urine albumin-to-creatinine ratio (UACR), renal vascular resistance (RVR), glomerular filtration rate (GFR), intraglomerular pressure (PGLO), efferent arteriole resistance (RE), afferent arteriolar resistance (RA), and renal plasma flow (RPF), and the above indicated biomarkers were assessed in youth aged 12–21 years with and without T1D of < 10 years duration.

Results

Fifty adolescents with T1D (16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 adolescents of comparable BMI without T1D (16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%) were enrolled. Adolescents with T1D demonstrated significantly higher GFR, RPF, RE, and PGLO than controls (39%, 33%, 74%, and 29%, respectively, all p < 0.0001). Adolescents with T1D also exhibited significantly lower RVR and RA than controls (25% and 155%, respectively, both p < 0.0001). YKL-40 and KIM-1 concentrations, respectively, were positively associated with GFR (r: 0.43, p = 0.002; r: 0.41, p = 0.003), RPF (r: 0.29, p = 0.08; r: 0.34, p = 0.04), UACR (r: 0.33, p = 0.02; r: 0.50, p = 0.0002), and PGLO (r: 0.45, p = 0.006; r: 0.52, p = 0.001) in adolescents with T1D.

Conclusions

Higher concentrations of biomarkers YKL-40 and KIM-1 may help define the risk for intraglomerular hemodynamic dysfunction in youth with T1D.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information.

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Data availability

The datasets generated and analyzed during this study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

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Acknowledgements

The authors thank the staff and participants of the CASPER and Renal-HEIR studies for their important contributions.

Funding

The CASPER and Renal-HEIR studies have been funded in whole or in part by NIH/NIDDK (K23-DK116720) and JDRF (2-SRA-2018–627-M-B). Funders had no role in the study design; collection, analysis, and interpretation of these data; writing the report; or the decision to submit the report. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the US government.

K.L.T. receives salary and research support from the NIH/NHLBI (K23 HL159292), Children’s Hospital Colorado Research Scholar Award, University of Colorado Diabetes Research Center (P30 DK116073), Ludeman Family Center for Women’s Health Research at the University of Colorado, and the Department of Pediatrics, Section of Endocrinology at the University of Colorado School of Medicine. C.R.P. is supported by NIH/NHLBI (R01 HL085757) and NIH/NIDDK (UH3 DK114866, U01 DK106962, R01 DK093770). R.G.N. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. P.B. receives salary and research support from NIDDK (R01 DK129211, R21 DK129720, K23 DK116720, UC DK114886, and P30 DK116073), JDRF (3-SRA-2022–1097-M-B, 2-SRA-2019–845-S-B, 3-SRA-2017–424-M-B), Boettcher Foundation, American Heart Association (20IPA35260142), Ludeman Family Center for Women’s Health Research at the University of Colorado, the Department of Pediatrics, Section of Endocrinology, and Barbara Davis Center for Diabetes at University of Colorado School of Medicine.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Section of Pediatric Endocrinology, Children’s Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Melissa J. Johnson, Kalie L. Tommerdahl, Carissa Vinovskis, Trenton Reinicke, Kristen J. Nadeau & Petter Bjornstad

  2. Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA

    Kalie L. Tommerdahl

  3. Ludeman Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Kalie L. Tommerdahl, Kristen J. Nadeau & Petter Bjornstad

  4. Section of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA

    Sushrut Waikar

  5. Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Chirag R. Parikh & Wassim Obeid

  6. Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA

    Robert G. Nelson

  7. Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands

    Daniel H. van Raalte

  8. Department of Biostatistics, Colorado School of Public Health, Aurora, CO, USA

    Laura Pyle

  9. Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, 13123 E. 16th AveBox B265, Aurora, CO, USA

    Petter Bjornstad

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  1. Melissa J. Johnson
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Contributions

M.J.J. analyzed and interpreted data and wrote the manuscript. K.L.T. analyzed and interpreted data and contributed to writing sections of the manuscript. C.V., S.W., and T.R. collected data and analyzed and interpreted data. T.R., L.P., and P.B. were responsible for data analyses. C.R.P. and W.O. analyzed and interpreted data. R.G.N., D.H.vR., K.J.N., and P.B. contributed to the development of the research idea and study design. All co-authors reviewed and edited the manuscript. P.B. is the guarantor of this work and, as such, has full access to the datasets and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Petter Bjornstad.

Ethics declarations

Ethics approval

The CASPER and Renal-HEIR cohorts have intentionally harmonized study protocols and were both approved by the Colorado Multiple Institutional Review Board (COMIRB).

Consent to participate

Participants and/or guardians provided written informed assent and/or consent, as appropriate.

Consent for publication

Not applicable.

Conflict of interest

M.J.J., K.L.T., C.V., S.W., T.R., W.O., R.G.N., L.P., and K.J.N. have no relationships relevant to the contents of this paper to disclose. C.R.P. reports serving as a member of the advisory board of and owning equity in RenalytixAI. He also serves as a consultant for Genfit and Novartis. D.H.vR. has served as a consultant and received honoraria from Boehringer Ingelheim and Eli Lilly, Merck, Novo Nordisk, and Sanofi and has received research operating funds from AstraZeneca, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, MSD, and Novo Nordisk. P.B. reports serving as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, LG Chemistry, Sanofi, Novo Nordisk, and Horizon Pharma. P.B. also serves on the advisory boards of AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk, and XORTX.

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Johnson, M.J., Tommerdahl, K.L., Vinovskis, C. et al. Relationship between biomarkers of tubular injury and intrarenal hemodynamic dysfunction in youth with type 1 diabetes. Pediatr Nephrol 37, 3085–3092 (2022). https://doi.org/10.1007/s00467-022-05487-4

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