Thyroid Dysfunction in Children with Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Thyroid abnormalities have been reported in children with chronic kidney disease (CKD), but the broad term "thyroid dysfunction" encompasses clinically distinct phenotypes. This study aimed to estimate the prevalence of subclinical hypothyroidism (SCH) and characterize other thyroid abnormalities separately.

PubMed/MEDLINE, Scopus, and Google Scholar were systematically searched according to PRISMA 2020. Eligible studies included patients aged 0-18 years with CKD stages 1-5, including kidney replacement therapy. The primary meta-analysis included peer-reviewed studies with an explicit or author-classified SCH definition and recoverable numerator and denominator data. Random-effects models used restricted maximum likelihood estimation with modified Hartung-Knapp inference.

Eleven studies involving 694 children were included. Seven peer-reviewed studies comprising 403 participants and 50 SCH cases contributed to the primary meta-analysis. The pooled SCH prevalence was 12.8% (95% CI, 9.2-17.6%), with a 95% prediction interval of 9.1-17.9% and no detected heterogeneity (I² = 0%). A binomial-normal generalized linear mixed model yielded a similar estimate of 12.4% (95% CI, 9.3-15.9%). Including one preprint increased prevalence to 14.8% and introduced substantial heterogeneity (I² = 65.9%). Overt hypothyroidism was reported sporadically, whereas low-T3/non-thyroidal-illness patterns were more frequent but unsuitable for quantitative synthesis.

Approximately one in eight children in the included CKD cohorts was classified as having SCH according to study-specific definitions; persistence and clinical significance remain uncertain. Current evidence is insufficient to support routine CKD-specific levothyroxine therapy. Standardized longitudinal studies are needed to clarify persistence, clinical significance, and potential treatment benefits.