Environmental and dietary triggers of hyperuricemia in chronic kidney disease: A cardiovascular perspective

BACKGROUND: Hyperuricemia-defined as serum urate above 6.8 mg/dL-is increasingly recognized as a risk marker and amplifier of chronic kidney disease (CKD) progression and cardiovascular disease (CVD), rather than merely a precursor to gout. In CKD, impaired renal urate clearance is exacerbated by environmental toxins, including airborne pollutants and heavy metals (lead, cadmium, arsenic), which disrupt tubular function and downregulate urate transporters (ABCG2, OAT1/3, URAT1). Dietary factors such as high-purine foods, fructose-rich beverages, and alcohol promote urate overproduction and reduce excretion, whereas DASH and Mediterranean dietary patterns are associated with lower serum urate and reduced cardiovascular risk. METHODS: This narrative review synthesizes current evidence from PubMed, Scopus, and Google Scholar on hyperuricemia in CKD, with a focus on environmental and dietary triggers and their cardiovascular implications. Priority was given to high-level evidence, including systematic reviews, meta-analyses, randomized controlled trials, and large cohort studies, alongside mechanistic and preclinical data. RESULTS: Mechanistically, uric acid promotes systemic inflammation, endothelial dysfunction, and oxidative stress via xanthine oxidase, contributing to microvascular and macrovascular injury. Genetic polymorphisms in urate transporters modulate susceptibility but represent non-modifiable risk factors. Observational studies consistently link elevated serum urate with adverse CKD and CVD outcomes; however, randomized trials of xanthine oxidase inhibitors have yielded conflicting results regarding clinical benefit. CONCLUSIONS: An integrated approach is required to manage hyperuricemia in CKD. Lifestyle strategies, including reducing dietary fructose, limiting alcohol, and adopting plant-forward diets, may lower serum urate, while mitigating environmental exposures may help preserve renal function. Pharmacotherapy should be individualized based on comorbidities and risk profiles. Despite supportive mechanistic and observational evidence, randomized trials remain inconclusive, highlighting the need for further research to clarify the cardiovascular impact of urate-lowering therapies and their role in CKD populations. A comprehensive, multidisciplinary approach may help reduce risk factors associated with CKD progression and cardiovascular disease.