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Associations between collagen X biomarker and linear growth velocity in a pediatric chronic kidney disease cohort

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An Editorial Commentary to this article was published on 26 July 2023

Abstract

Background

Collagen X biomarker (CXM) is a novel biomarker of linear growth velocity. We investigated whether CXM correlated with measured growth velocity in children with impaired kidney function.

Methods

We used data from children aged 2 through 16 years old enrolled in the Chronic Kidney Disease in Children (CKiD) study. We assessed the association between CXM level and growth velocity based on height measurements obtained at study visits using linear regression models constructed separately by sex, with and without adjustment for CKD covariates. Linear mixed-effects models were used to capture the between-individual and within-individual CXM changes over time associated with concomitant changes in growth velocity from baseline through follow-up.

Results

A total of 967 serum samples from 209 participants were assayed for CXM. CXM correlated more strongly in females compared to male participants. After adjustment for growth velocity and CKD covariates, only proteinuria in male participants affected CXM levels. Finally, we quantified the between- and within-participant associations between CXM level and growth velocity. A between-participant increase of 24% and 15% in CXM level in females and males, respectively, correlated with a 1 cm/year higher growth velocity. Within an individual participant, on average, 28% and 13% increases in CXM values in females and males, respectively, correlated with a 1 cm/year change in measured growth.

Conclusions

CXM measurement is potentially a valuable aid for monitoring growth in pediatric CKD. However, future research, including studies of CXM metabolism, is needed to clarify whether CXM can be a surrogate of growth in children with CKD.

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Acknowledgements

Data in this manuscript were collected by the Chronic Kidney Disease in children prospective cohort study (CKiD) with clinical coordinating centers (Principal Investigators) at Children’s Mercy Hospital and the University of Missouri – Kansas City (Bradley Warady, MD) and Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Muñoz, PhD and Derek Ng, PhD) at the Johns Hopkins Bloomberg School of Public Health. The CKiD Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U24-DK-082194, U24-DK-66116). The CKID website is located at https://www.statepi.jhsph.edu/ckid and a list of CKiD collaborators can be found at https://statepi.jhsph.edu/ckid/site-investigators.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): K12HD00139.

Author information

Authors and Affiliations

  1. Division of Nephrology, Children’s National Hospital/Department of Pediatrics, George Washington School of Medicine, 111 Michigan Ave, Washington, NWDC, USA

    Denver D. Brown

  2. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Jennifer Roem & Derek K. Ng

  3. Research Center, Shriners Hospital for Children, Portland, OR, USA

    Ryan F. Coghlan, Brian Johnstone & William Horton

  4. Department of Orthopaedics & Rehabilitation, Oregon Health & Science University, Portland, OR, USA

    Brian Johnstone

  5. Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA

    Brian Johnstone & William Horton

  6. Division of Pediatric Nephrology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Susan L. Furth

  7. Division of Pediatric Nephrology, Children’s Mercy Hospital, Kansas City, MO, USA

    Bradley A. Warady

  8. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA

    Michal L. Melamed

  9. Division of Endocrinology, Children’s National Hospital/Department of Pediatrics, George Washington School of Medicine, Washington, DC, USA

    Andrew Dauber

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  • Bradley Warady
  • , Susan Furth
  • , George Schwartz
  • , Alvaro Muñoz
  •  & Derek Ng

Corresponding author

Correspondence to Denver D. Brown.

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Conflict of interest

A.D consults for Ascendis, Novo Nordisk, BridgeBio, and Biomarin. The remaining authors have no relevant disclosures.

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Denver D. Brown and Jennifer Roem are co-first authors.

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Brown, D.D., Roem, J., Ng, D.K. et al. Associations between collagen X biomarker and linear growth velocity in a pediatric chronic kidney disease cohort. Pediatr Nephrol 38, 4145–4156 (2023). https://doi.org/10.1007/s00467-023-06047-0

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