儿童高尿酸血症与代谢综合征的关联机制及治疗进展

Mechanisms linking hyperuricemia and metabolic syndrome in children and advances in treatment

摘要

儿童高尿酸血症(HUA)与代谢综合征(MetS)是儿科内分泌代谢领域日益受到关注的健康问题。两者常并存且可能相互促进,从而增加儿童期及远期心血管代谢疾病风险。本文综述儿童HUA与MetS的流行病学特征、共同病理生理机制、临床关联和治疗进展,旨在为高危儿童的早期识别及以生活方式干预和药物治疗为基础的综合管理提供理论依据与实践参考。

Abstract

Hyperuricemia (HUA) and metabolic syndrome (MetS) in children are increasingly recognized as important concerns in pediatric endocrinology and metabolism. The two conditions frequently coexist and may reinforce each other, thereby increasing cardiometabolic risk during childhood and later life. This review summarizes the epidemiological characteristics, shared pathophysiological mechanisms, clinical associations, and treatment advances of pediatric HUA and MetS, in order to provide a theoretical basis and practical reference for the early identification of high-risk children and comprehensive management centered on lifestyle interventions and pharmacological therapy.

关键词

高尿酸血症 / 儿童 / 代谢综合征 / 病理生理机制

Key words

hyperuricemia / children / metabolic syndrome / pathophysiological mechanisms

[1] 向凤玲, 王远坤, 王小燕, 等. 中国儿童青少年高尿酸血症患病率的Meta分析[J].中国全科医学, 2025, 28(33): 4206-4213.
Xiang FL, Wang YK, Wang XY, et al. The prevalence of hyperuricemia among children and adolescents in China: A meta-analysis[J]. Chin Gen Pract, 2025, 28(33): 4206-4213. (in Chinese)
[2] Faienza MF, Cognetti E, Farella I, et al. Dietary fructose: From uric acid to a metabolic switch in pediatric metabolic dysfunction-associated steatotic liver disease[J]. Crit Rev Food Sci Nutr, 2025, 65(23): 4583-4598.
[3] 朱博文, 王同帅, 王星云, 等.血尿酸水平对儿童青少年代谢综合征及其组分的影响[J].中国儿童保健杂志, 2025, 33(5): 489-496.
Zhu BW, Wang TS, Wang XY, et al. Effect of serum uric acid levels on metabolic syndrome and its components in children and adolescents[J]. Chin J Child Health Care, 2025, 33(5): 489-496. (in Chinese)
[4] Zhang J, Sun N, Zhang W, et al. The impact of uric acid on musculoskeletal diseases: Clinical associations and underlying mechanisms[J]. Front Endocrinol, 2025, 16: 1515176.
[5] Moulin-Mares SRA, Oliosa PR, Faria ER, et al. Association of uric acid with cardiovascular risk in Brazilian children and adolescents[J]. Nutr Metab Cardiovasc Dis, 2021, 31(1): 314-321.
[6] Stiburkova B, Lukesova M, Zeman J. Pediatrics hyperuricemia in clinical practice: A retrospective analysis in 1 753 children and adolescents with hyperuricemia[J]. Jt Bone Spine, 2025, 92(1): 105796.
[7] You SY, Cho SI, Suh JS. Clinical and dietary risk factors of hyperuricemia in Korean children and adolescents: The 8th Korea National Health and Nutrition Examination Survey[J]. Kidney Res Clin Pract, 2025, 44(6): 950-959.
[8] Kitoh T, Yamana T, Imura H, et al. Age and gender-specific reference intervals for uric acid level and hyperuricemia in children with Down syndrome[J]. Pediatr Int, 2025, 67(1): e15863.
[9] 高雨霏,张力之,朱文萱,等.中国儿童青少年代谢综合征患病率的Meta分析[J].数理医药学杂志, 2024, 37(12): 922-934.
Gao YF, Zhang LZ, Zhu WX, et al. Prevalence of metabolic syndrome in Chinese children and adolescents: A Meta-analysis[J]. J Math Med, 2024, 37(12): 922-934. (in Chinese)
[10] 叶佩玉,赵小元,闫银坤,等.儿童高尿酸血症与心血管代谢异常发生风险[J].中华流行病学杂志, 2021, 42(3): 433-439.
Ye PY, Zhao XY, Yan YK, et al. Association between hyperuricemia and incidence risk for cardiometabolic abnormity in children[J]. Chin J Epidemiol, 2021, 42(3): 433-439. (in Chinese)
[11] Xie L, Mo PKH, Tang Q, et al. Skeletal muscle mass has stronger association with the risk of hyperuricemia than body fat mass in obese children and adolescents[J]. Front Nutr, 2022, 9: 792234.
[12] Reis LN, Borfe L, Brand C, et al. Food consumption is associated with hyperuricemia in boys[J]. High Blood Press Cardiovasc Prev, 2020, 27(5): 409-415.
[13] Kim HJ. Association between hyperuricemia and dehydration in children with acute gastroenteritis[J]. Pediatr Emerg Care, 2026, 42(2): 91-95.
[14] Taner S, Gezici E, Unal A, et al. The association of obesity and hyperuricemia with ambulatory blood pressure in children[J]. Pediatr Nephrol, 2025, 40(3): 787-796.
[15] Elitok GK, Duru NS, Elevli M, et al. Prevalence of metabolic syndrome in middle school children and evaluation of components of metabolic syndrome[J]. Sisli Etfal Hastan Tip Bul, 2019, 53(4): 403-408.
[16] Cassano V, Crescibene D, Hribal ML, et al. Uric acid and vascular damage in essential hypertension: Role of insulin resistance[J]. Nutrients, 2020, 12(9): 2509.
[17] Zhang Y, Zhang H, Rong S, et al. NMR spectroscopy based metabolomics confirms the aggravation of metabolic disorder in metabolic syndrome combined with hyperuricemia[J]. Nutr Metab Cardiovasc Dis, 2021, 31(8): 2449-2457.
[18] Yu W, Xie D, Yamamoto T, et al. Mechanistic insights of soluble uric acid-induced insulin resistance: Insulin signaling and beyond[J]. Rev Endocr Metab Disord, 2023, 24(2): 327-343.
[19] Timsans J, Kauppi J, Rantalaiho V, et al. Serum uric acid is associated with insulin resistance in non-diabetic subjects[J]. J Clin Med, 2025, 14(8): 2621.
[20] Vareldzis R, Perez A, Reisin E. Hyperuricemia: An intriguing connection to metabolic syndrome, diabetes, kidney disease, and hypertension[J]. Curr Hypertens Rep, 2024, 26(6): 237-245.
[21] González-Domínguez Á, Belmonte T, Domínguez-Riscart J, et al. Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance[J]. J Transl Med, 2023, 21(1): 559.
[22] Kim YJ, Kim S, Seo JH, et al. Prevalence and associations between metabolic syndrome components and hyperuricemia by race: Findings from US population, 2011-2020[J]. Arthritis Care Res, 2024, 76(8): 1195-1202.
[23] Zhang X, Liu J. Regulating lipid metabolism in gout: A new perspective with therapeutic potential[J]. Int J Gen Med, 2024, 17: 5203-5217.
[24] Liu N, Sun Q, Xu H, et al. Hyperuricemia induces lipid disturbances mediated by LPCAT3 upregulation in the liver[J]. FASEB J, 2020, 34(10): 13474-13493.
[25] Liu Y, Li Z, Xu Y, et al. Uric acid and atherosclerosis in patients with chronic kidney disease: Recent progress, mechanisms, and prospect[J]. Kidney Dis (Basel), 2025, 11(1): 112-127.
[26] Yu J, Liu X, Ji H, et al. Distribution of serum uric acid concentration and its association with lipid profiles: A single-center retrospective study in children aged 3 to 12 years with adenoid and tonsillar hypertrophy[J]. Lipids Health Dis, 2023, 22(1): 48.
[27] Chiang YF, Huang KC, Huang YJ, et al. Hinokitiol modulates Nrf2/HO-1 signaling, autophagy, and URAT1 in hyperuricemia and oxidative stress models of renal injury[J]. Free Radic Biol Med, 2025, 238: 169-178.
[28] Banik SD, Avila-Nava A, Lugo R, et al. Association between low-grade inflammation and hyperuricemia in adults with metabolic syndrome in Yucatán, México[J]. Can J Diabetes, 2022, 46(4): 369-374.
[29] Qian Y, Zhang Y, Chen Y, et al. Linarin attenuates hyperuricemic nephropathy by modulating Nrf2/Keap1 and TLR4/NF-κB signaling pathways: Linarin attenuates hyperuricemic nephropathy[J]. Phytomedicine, 2025,139:156440.
[30] Koutsaliaris IK, Moschonas IC, Pechlivani LM, et al. Inflammation, oxidative stress, vascular aging and atherosclerotic ischemic stroke[J].Curr Med Chem, 2022, 29(34): 5496-5509.
[31] Masi S, Georgiopoulos G, Alexopoulos G, et al. The complex relationship between serum uric acid, endothelial function and small vessel remodeling in humans[J]. J Clin Med, 2020, 9(7): 2027.
[32] Zhang J, Lei W, Zhou J, et al. Uric acid promotes aortic valve calcification via mediating valve interstitial cell osteogenic differentiation and endothelial dysfunction[J]. FASEB J, 2025, 39(6): e70437.
[33] Wang R, Bai Z, Zhang D, et al. Mediating effects of insulin resistance on the development of hypertension associated with elevated serum uric acid: A prospective cohort study[J]. J Hum Hypertens, 2022, 36(8): 760-766.
[34] Goli P, Riahi R, Daniali SS, et al. Association of serum uric acid concentration with components of pediatric metabolic syndrome: A systematic review and meta-analysis[J]. J Res Med Sci, 2020, 25: 43.
[35] Rutters F, den Braver NR, Lakerveld J, et al. Lifestyle interventions for cardiometabolic health[J]. Nat Med, 2024, 30(12): 3455-3467.
[36] Lambert JO, Beck A, Showell NN. Lifestyle interventions in pediatric primary care[J]. Pediatr Clin North Am, 2024, 71(5): 943-955.
[37] Li C, Lu J, Lyu Z, et al. Clinical practice consensus statement 2025: Management of hyperuricemia and gout in adolescents[J]. Int J Rheum Dis, 2025, 28(7): e70378.
[38] Tagi VM, Samvelyan S, Chiarelli F. Metabolic syndrome in children[J]. Minerva Pediatr, 2020, 72(4): 312-325.
[39] Barenbaum SR, Kumar RB, Aronne LJ. Management of medication-induced weight gain[J]. Gastroenterol Clin North Am, 2023, 52(4): 751-760.
[40] Ebstein E, Ottaviani S. Managing gout in patients with metabolic syndrome[J]. Drugs Aging, 2024,41(8):653-663.
[41] Wu J, Aga L, Tang L, et al. Lacticaseibacillus paracasei JS-3 Isolated from "Jiangshui" ameliorates hyperuricemia by regulating gut microbiota and iTS metabolism[J]. Foods, 2024,13(9):1371.

基金资助

深圳市医疗卫生三名工程项目资助(SZSM202311021)