Drug-induced hyperuricemia: multi-pathway regulation, causative drugs, and individualized management strategies

Hyperuricemia, a prevalent metabolic disorder, is not only the primary cause of gout but also an independent risk factor for various chronic conditions, including hypertension, cardiovascular and cerebrovascular diseases, and diabetes mellitus, thereby posing a significant threat to multi-organ health. Iatrogenic factors represent a key pathogenic trigger for hyperuricemia. With the expanding spectrum of clinical medications and the widespread adoption of polypharmacy, drug-induced hyperuricemia (DIH) now affects up to 25% of hospitalized patients and over 80% of transplant recipients on cyclosporine, emerging as a critical challenge to medication safety and therapeutic efficacy. We conducted a comprehensive literature search across PubMed, Embase, and Web of Science, systematically analyzed 76 relevant high-quality studies, and summarized the core pathogenic pathways, causative drugs, and individualized management strategies of DIH. Focusing on pharmacological mechanisms and clinical translation, this review delineates two pivotal pathogenic pathways of DIH: one involving dysregulation of key transporters that control renal uric acid reabsorption and secretion, and the other characterized by enhanced uric acid production via disruption of purine metabolism. We summarize over 10 classes of causative drugs and their molecular mechanisms, thereby advancing current understanding of DIH pathogenesis. Finally, we integrate management strategies encompassing medication adjustment, urate-lowering therapy, and non-pharmacological interventions, providing a scientific basis for rational prescribing, screening of high-risk populations, and the development of safer therapeutic agents.