Hyperuricemia in Children and Adolescents: Renal Consequences, Cardiometabolic Risk, and Emerging Therapeutic Strategies

Serum uric acid (SUA) levels in children and adolescents have risen substantially over recent decades, driven by the global surge in childhood obesity, high-fructose dietary patterns, and the increasing prevalence of metabolic syndrome in younger populations. Whereas clinical gout — the hallmark of uric acid pathology in adults — is rare in pediatric patients, asymptomatic hyperuricemia is now recognized as a clinically meaningful condition in children, with prevalence estimates ranging from 5% to over 25% in obese youth and up to 38% in pediatric chronic kidney disease (CKD) cohorts. This trajectory places pediatric hyperuricemia firmly at the intersection of nephrology, endocrinology, and cardiovascular medicine, yet clinical guidelines and therapeutic frameworks for children remain underdeveloped compared to the adult literature.

The kidney lies at the center of uric acid homeostasis and bears the primary burden of its dysregulation in children. Uric acid nephrolithiasis is an established and growing cause of stone disease in pediatric patients, while longitudinal data from the CKD in Children (CKiD) cohort have demonstrated that elevated SUA independently accelerates CKD progression and is associated with incident hypertension in this population. Recent evidence from the CKiD study further suggests that allopurinol significantly reduces SUA levels and may attenuate disease progression in children with CKD — a finding with substantial therapeutic implications. Beyond structural renal disease, hyperuricemia is increasingly implicated in the pathogenesis of childhood hypertension through endothelial dysfunction and renin–angiotensin system activation, and as a metabolic co-driver alongside insulin resistance, dyslipidemia, and visceral adiposity. The acute management of tumor lysis syndrome, a nephrology emergency characterized by sudden hyperuricemia-driven renal failure, represents a further critical dimension of uric acid biology in the pediatric setting.
Despite this growing burden, fundamental questions remain unanswered: What are the appropriate SUA reference ranges across pediatric age, sex, and pubertal stage? At what threshold does intervention become warranted in asymptomatic children? What are the long-term renal and cardiovascular outcomes of childhood hyperuricemia tracked into adulthood? How do genetic variants in urate transporters (SLC22A12, ABCG2) interact with dietary and metabolic exposures in pediatric populations? And which pharmacological agents — allopurinol, febuxostat, rasburicase, or emerging uricosuric therapies — are safe and effective for use in children across different clinical contexts?

This Research Topic aims to consolidate the current evidence base and catalyze new research across the full spectrum of pediatric hyperuricemia — from its molecular underpinnings and epidemiology to its clinical consequences and management. We welcome original research, systematic reviews and meta-analyses, clinical trial reports, and perspective articles addressing any of the subtopics listed below.

• Epidemiology and reference ranges of serum uric acid in pediatric populations across age, sex, ethnicity, and pubertal stage
• Mechanisms of hyperuricemia-induced renal injury and CKD progression in children
• Uric acid nephrolithiasis: pathophysiology, diagnosis, and management in pediatric patients
• Hyperuricemia as an independent risk factor for childhood hypertension and endothelial dysfunction
• Uric acid in the context of pediatric metabolic syndrome, obesity, and insulin resistance
• Genetic determinants of uric acid metabolism in children: urate transporter variants and purine pathway disorders
• Tumour lysis syndrome: prevention, monitoring, and acute management of hyperuricemia in pediatric oncology
• Pharmacological management of hyperuricemia in children: efficacy and safety of allopurinol, febuxostat, rasburicase, and novel agents
• Dietary and lifestyle interventions for hyperuricemia in children and adolescents
• Long-term cardiovascular and renal outcomes of childhood hyperuricemia: cohort and longitudinal studies