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Prevalence and outcomes of fragility: a frailty-inflammation phenotype in children with chronic kidney disease

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Abstract

Background

Frailty is a condition of decreased physiologic reserve and increased vulnerability to stressors. Frailty in combination with inflammation has been associated with increased mortality risk in adults with advanced chronic kidney disease (CKD). This study aimed to investigate prevalence and outcomes associated with a frailty-inflammation phenotype, or “fragility,” in children with CKD.

Methods

We analyzed 557 children (age 6–19 years, eGFR 30–90 ml/min/1.73 m2) from the Chronic Kidney Disease in Children (CKiD) study. Based on adult models, the CKiD fragility model included four indicators: (1) suboptimal growth/weight gain (BMI < 5th percentile-for-height-age, deceleration ≥ 10 BMI-for-height-age percentiles/1 year, height-for-age percentile < 3rd or deceleration ≥ 10 height percentiles/1 year); (2) low muscle mass (mid-upper-arm circumference < 5th percentile or deceleration ≥ 10 percentiles/1 year); (3) fatigue (parent/child report); (4) inflammation (CRP > 3 mg/l). Logistic regression was used to evaluate association of fragility indicators with three adverse outcomes: frequent infection (> 1 per year/3 years), hospitalization (any), and rapid CKD progression (decline in eGFR > 30% or initiation of renal replacement therapy within 3 years).

Results

Prevalence of fragility indicators 1 year after study entry were 39% (suboptimal growth/weight gain), 62% (low muscle mass), 29% (fatigue), and 18% (inflammation). Prevalence of adverse outcomes during the subsequent 3 years were 13% (frequent infection), 22% (hospitalization), and 17% (rapid CKD progression). Children with ≥ 3 fragility indicators had 3.16-fold odds of frequent infection and 2.81-fold odds of hospitalization, but did not have rapid CKD progression.

Conclusions

A fragility phenotype, characterized by the presence of ≥ 3 indicators, is associated with adverse outcomes, including infection and hospitalization in children with CKD.

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Data availability

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 website is located at https://statepi.jhsph.edu/ckid.

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Funding

The CKiD study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver 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).

Author information

Authors and Affiliations

  1. Department of Nephrology, Children’s National Health System, 111 Michigan Ave NW, Washington DC, 20010, USA

    Kristen Sgambat & Asha Moudgil

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

    Matthew B. Matheson

  3. University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Stephen R. Hooper

  4. Pediatric Nephrology, Children’s Mercy Kansas City, Kansas City, MO, USA

    Bradley Warady

  5. Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Susan Furth

Authors
  1. Kristen Sgambat
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  2. Matthew B. Matheson
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  3. Stephen R. Hooper
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  4. Bradley Warady
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  5. Susan Furth
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  6. Asha Moudgil
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Corresponding author

Correspondence to Kristen Sgambat.

Ethics declarations

The CKiD study (NCT00327860) was approved by an external study monitoring board appointed by the National Institute of Diabetes and Digestive and Kidney Diseases and by the institutional review board of each participating center, including Children’s National Health System. Informed consent of all individual participants included in the study was obtained by each center and the study was conducted in accordance with the Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Sgambat, K., Matheson, M.B., Hooper, S.R. et al. Prevalence and outcomes of fragility: a frailty-inflammation phenotype in children with chronic kidney disease. Pediatr Nephrol 34, 2563–2569 (2019). https://doi.org/10.1007/s00467-019-04313-8

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  • DOI: https://doi.org/10.1007/s00467-019-04313-8

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