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Tumor necrosis factor-alpha is associated with mineral bone disorder and growth impairment in children with chronic kidney disease

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Abstract

Background

Mineral and bone disorder (MBD) and growth impairment are common complications of pediatric chronic kidney disease (CKD). Chronic inflammation detrimentally affects bone health and statural growth in non-CKD settings, but the impact of inflammation on CKD-MBD and growth in pediatric CKD remains poorly understood. This study assessed associations between inflammatory cytokines with biomarkers of CKD-MBD and statural growth in pediatric CKD.

Methods

This is a cross-sectional study of children with predialysis CKD stages II–V. Cytokines (IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, interferon-γ), bone alkaline phosphatase (BAP), and procollagen type 1 N-terminal propeptide (P1NP) were measured at the same time as standard CKD-MBD biomarkers. Associations between cytokines, CKD-MBD biomarkers, and height z-score were assessed using linear regression analysis.

Results

Among 63 children, 52.4% had stage 3 CKD, 76.2% non-glomerular CKD etiology, and 21% short stature. TNF-α was the only cytokine associated with parathyroid hormone (PTH) independent of glomerular filtration rate. After stratification by low, medium, and high TNF-α tertiles, significant differences in PTH, serum phosphorus, alkaline phosphatase, BAP, P1NP, and height z-score were found. In a multivariate analysis, TNF-α positively associated with phosphorus, PTH, and alkaline phosphatase and inversely associated with height z-score, independent of kidney function, age, sex, and active vitamin D analogue use.

Conclusions

TNF-α is positively associated with biomarkers of CKD-MBD and inversely associated with height z-score, indicating that inflammation likely contributes to the development of CKD-MBD and growth impairment in pediatric CKD. Prospective studies to definitively assess causative effects of inflammation on bone health and growth in children with CKD are warranted.

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Acknowledgments

The authors thank Samantha Pellegrino for help with data collection and Dajana Borova and Haneen Aljayyousi for the regulatory support of this study.

Funding

This study was supported in part by the National Institutes of Health National Center for Advancing Translational Sciences UL1TR00457 and UL1TR002384 awarded to the Clinical and Translational Science Center, Weill Cornell Medicine, Rohr Family Clinical Scholar Award, and by the Department of Pediatrics at Weill Cornell Medicine. OA is supported by the K08 DK114558 from the NIH NIDDK.

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  1. Weill Cornell Medical College, Department of Pediatrics, New York, NY, USA

    Kelly Meza, Sharmi Biswas, Anuradha Gajjar, Eduardo Perelstein, Juhi Kumar & Oleh Akchurin

  2. Weill Cornell Medical College, Department of Medicine, Clinical and Translational Science Center, New York, NY, USA

    Yuan-Shan Zhu

  3. Weill Cornell Medicine, New York-Presbyterian Phyllis and David Komansky Children’s Hospital, 505 East 70th Street-HT 388, New York, NY, 10021, USA

    Anuradha Gajjar, Eduardo Perelstein, Juhi Kumar & Oleh Akchurin

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  1. Kelly Meza
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Meza, K., Biswas, S., Zhu, YS. et al. Tumor necrosis factor-alpha is associated with mineral bone disorder and growth impairment in children with chronic kidney disease. Pediatr Nephrol 36, 1579–1587 (2021). https://doi.org/10.1007/s00467-020-04846-3

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