Hyperuricemia: Current state and prospects

Hyperuricemia (HU) is a global health concern characterized by elevated levels of uric acid (UA) in the blood. It is diagnosed when UA levels exceed 420 µmol L−1 (7 mg/dL) for men and 350 µmol L−1 (6 mg/dL) for women. The lack of the enzyme uricase in humans, which degrades UA to allantoin, contributes to the high UA levels, leading to its precipitation and associated health risks. HU can be induced by various factors, including purine-rich diets, genetic predisposition, obesity, impaired kidney function, certain medications, and environmental factors. This condition is linked to several complications, such as cardiovascular diseases (CVDs), gout, metabolic syndrome (MS), renal dysfunction, and neurodegenerative diseases. The review emphasizes the multifactorial nature of HU, highlighting the complex interplay between genetic, dietary, lifestyle, and environmental factors.

Association with Health Risks

HU is associated with significant health risks, particularly cardiovascular diseases (CVDs) and gout. Elevated UA levels are linked to an increased risk of coronary artery disease, hypertension, stroke, and metabolic syndrome. The review explores the mechanisms underlying these associations, such as endothelial dysfunction, oxidative stress, inflammation, and the activation of the renin-angiotensin-aldosterone system. Gout, a common consequence of HU, results from the deposition of urate crystals in joints, leading to painful inflammation. The review also discusses the relationship between HU and renal dysfunction, emphasizing the bidirectional nature of this association, where renal impairment both contributes to and results from HU. Additionally, the potential neuroprotective effects of UA in neurodegenerative diseases like Alzheimer's are considered, although further research is needed to confirm these findings.

Current Diagnostic Approaches

The primary diagnostic method for HU is the measurement of serum UA levels. While this approach is straightforward, the review highlights advancements in diagnostic imaging and omics technologies that enhance the precision of HU diagnosis. Techniques like ultrasound and dual-energy computed tomography allow non-invasive visualization of urate crystal deposits, aiding in the diagnosis and severity assessment of HU. The review also discusses the potential of novel biomarkers and synthetic biology therapies, such as reprogramming E. coli to monitor serum UA levels, which could revolutionize early detection and personalized management of HU.

Treatment Strategies

Pharmacological interventions are central to managing HU, particularly when lifestyle modifications are insufficient. The review discusses the use of xanthine oxidase (XO) inhibitors like allopurinol and febuxostat as first-line treatments, along with uricosuric agents for patients who do not respond to monotherapy. However, treatment resistance and refractory disease remain challenges, prompting the exploration of novel drug targets and combination therapies. The review also highlights the potential of Chinese herbal medicines and natural products as alternative treatments with fewer side effects. Additionally, the role of gut microbiota in UA metabolism is explored, with probiotics emerging as promising interventions to regulate UA levels.

Role of Lifestyle Factors

Lifestyle factors, including diet, exercise, and sleep, play a crucial role in the management of HU. The review emphasizes the concept of "food as medicine," advocating for dietary adjustments to control UA levels. Regular physical activity is recommended to promote weight loss and improve insulin sensitivity, both of which are crucial for managing HU. However, the review also cautions against intense exercise, which may exacerbate HU. The importance of a holistic approach to lifestyle modification, including reducing alcohol and fructose intake, maintaining adequate hydration, and promoting good sleep hygiene, is stressed as essential for preventing or managing HU.

Prospective Directions

The review concludes by discussing the future directions for HU research and management. Advances in genomics have identified genetic markers associated with HU, paving the way for precision medicine approaches that tailor treatment based on individual genetic profiles. The review also highlights the potential of microbiota-targeted interventions and anti-inflammatory agents as emerging therapies. However, challenges remain, such as determining the optimal duration of pharmacological interventions and understanding the long-term effects of HU management on cardiovascular outcomes. Collaborative efforts among researchers, clinicians, and pharmaceutical industries are deemed essential for advancing our understanding and improving patient outcomes.

Conclusions

Hyperuricemia represents a complex metabolic disorder with significant implications for health. The review by Weizheng Zhang provides a detailed analysis of the current understanding of HU, highlighting its causes, associated risks, diagnostic methods, treatment options, and future research prospects. As our knowledge of HU evolves, the integration of precision medicine, lifestyle modifications, and novel therapeutic approaches holds promise for improving the quality of life for individuals with HU.

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The study was recently published in the Chronic Metabolic Diseases

Chronic Metabolic Diseases (CMD) is dedicated to advancing our knowledge of the epidemiology, pathophysiology, prevention, and treatment of chronic metabolic diseases. We publish works from basic biomedical to translational and clinical research on metabolism.

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