Tsang Yik Pui, Aryeh Kayenat S, Wang Kai, Himmelfarb Jonathan, Yeung Catherine K, Kelly Edward J
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA.
Barbara T. Murphy Division of Nephrology, Samuel Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Expert Opin Drug Saf. 2025 Jul 4:1-26. doi: 10.1080/14740338.2025.2525970.
Kidney diseases, including chronic kidney disease and acute kidney injury, pose major global health challenges due to their high prevalence and impact on morbidity and mortality. Despite medical advances, there remains an urgent need for improved drug development and therapeutic strategies to treat these conditions.
This review examines how renal transporters influence drug handling, highlighting the impact of altered transporter function on toxin accumulation, organ injury, and systemic toxicity. We also address pharmacokinetic and pharmacodynamic changes in kidney diseases, recent advances in preclinical models like microphysiological systems, emerging therapies, and biomarkers for early detection and monitoring.
A robust understanding of transporter function and disease-specific pharmacokinetic shifts is crucial for optimizing drug development. While MPS show promise in predicting drug responses and nephrotoxicity by more accurately simulating human kidney physiology, current hurdles include complexity, cost, and scalability. Emerging biomarkers require stringent validation to ensure specificity and reliability in kidney disease. Targeting transporters offers novel therapeutic and drug repurposing opportunities. Moving forward, refining and validating these models and biomarkers, alongside patient-tailored therapies, will improve personalized medicine and management. Attentive integration of these innovations could significantly reduce morbidity and improve outcomes worldwide for patients with kidney disease.
肾脏疾病,包括慢性肾脏病和急性肾损伤,因其高患病率以及对发病率和死亡率的影响,构成了重大的全球健康挑战。尽管医学取得了进步,但仍迫切需要改进药物开发和治疗策略来治疗这些疾病。
本综述探讨了肾脏转运体如何影响药物处置,强调了转运体功能改变对毒素蓄积、器官损伤和全身毒性的影响。我们还讨论了肾脏疾病中的药代动力学和药效学变化、微生理系统等临床前模型的最新进展、新兴疗法以及用于早期检测和监测的生物标志物。
深入了解转运体功能和疾病特异性药代动力学变化对于优化药物开发至关重要。虽然微生理系统通过更准确地模拟人体肾脏生理学在预测药物反应和肾毒性方面显示出前景,但当前的障碍包括复杂性、成本和可扩展性。新兴生物标志物需要严格验证,以确保在肾脏疾病中的特异性和可靠性。靶向转运体提供了新的治疗和药物重新利用机会。展望未来,完善和验证这些模型和生物标志物,以及个性化治疗,将改善个性化医疗和管理。认真整合这些创新可以显著降低全球肾病患者的发病率并改善治疗结果。