Prevalence and Outcomes of Fragility: a Frailty-inflammation Phenotype in Children with Chronic Kidney Disease

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 m) 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.