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Enhancing therapeutic strategies and drug development for patients with kidney disease
Yik Pui Tsang1, Kayenat S Aryeh1, Kai Wang1
1Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA.
Introduction:
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.
Areas Covered:
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.
Expert Opinion:
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.
Insights
Understanding renal transporters is key for developing better kidney disease treatments. Advances in models and biomarkers offer new therapeutic strategies and personalized medicine for patients with kidney disease.
Area of Science:
- Nephrology
- Pharmacology
- Drug Development
Background:
- Kidney diseases, including chronic kidney disease and acute kidney injury, represent a significant global health burden.
- There is a critical need for enhanced drug development and therapeutic interventions for kidney diseases.
Purpose of the Study:
- To review the role of renal transporters in drug handling and their impact on kidney injury.
- To discuss pharmacokinetic and pharmacodynamic alterations in kidney diseases.
- To explore advancements in preclinical models, emerging therapies, and biomarkers for kidney disease.
Main Methods:
- Literature review focusing on renal transporters, drug disposition, and kidney disease.
- Analysis of pharmacokinetic and pharmacodynamic changes.
- Evaluation of microphysiological systems (MPS) and emerging biomarkers.
Main Results:
- Altered renal transporter function can lead to toxin accumulation, organ damage, and systemic toxicity.
- Microphysiological systems show potential for predicting drug response and nephrotoxicity.
- Emerging biomarkers require validation for reliable detection and monitoring in kidney disease.
Conclusions:
- Optimizing drug development requires understanding transporter function and disease-specific pharmacokinetic shifts.
- Targeting transporters presents opportunities for novel therapies and drug repurposing.
- Validated models and biomarkers, coupled with personalized therapies, are essential for improving kidney disease management and patient outcomes.
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